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Ticagrelor monotherapy beats DAPT in STEMI
, a major randomized trial.
“This is the first report assessing the feasibility of ticagrelor monotherapy after short-term DAPT for STEMI patients with drug-eluting stents,” Byeong-Keuk Kim, MD, PhD, noted at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
The positive results were consistent with the earlier TWILIGHT study (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention), which also showed clinical benefit at 1 year for 3 months of DAPT followed by ticagrelor (Brilinta) monotherapy, albeit only in PCI patients without an acute coronary syndrome (ACS) or with non-STEMI ACS (N Engl J Med. 2019 Nov 21;381[21]:2032-42).
TICO-STEMI was a prespecified substudy involving the 1,103 STEMI patients included in the previously reported parent 38-center South Korean TICO (Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI) study of 3,056 ACS patients treated with a second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stent (JAMA. 2020 Jun 16;323[23]:2407-16).
The primary outcome in TICO-STEMI was the 12-month composite rate of net adverse clinical events, composed of major bleeding, all-cause mortality, acute MI, stroke, stent thrombosis, or target vessel revascularization. In an intention-to-treat analysis, the rate was 5.0% in the 12-month DAPT group and 3.7% with ticagrelor monotherapy after 3 months of DAPT, for a 27% relative risk reduction which didn’t achieve statistical significance. However, in an as-treated analysis, the between-group difference in the primary endpoint was stronger: a 5.2% incidence with 12 months of DAPT and 2.3% with ticagrelor monotherapy, for a relative risk reduction of 56%, which was statistically significant.
Major bleeding, one of two key secondary endpoints, was a different story: The incidence within 12 months by intention-to-treat was 2.9% with 12 months of DAPT compared to 0.9% with ticagrelor monotherapy, for a statistically significant 68% relative risk reduction in favor of ticagrelor monotherapy. In contrast, there was no between-group difference in the other secondary endpoint composed of major adverse cardio- and cerebrovascular events: 2.7% with ticagrelor monotherapy, 2.5% with 12 months of DAPT.
In the subgroup of TICO-STEMI patients at high bleeding risk, ticagrelor monotherapy was associated with a 12-month major bleeding rate of 1.8%, compared to 6.3% with a full year of DAPT. Conversely, in patients who underwent complex PCI, ticagrelor monotherapy was associated with a 4.9% rate of major adverse cardio- and cerebrovascular events through 1 year, numerically greater than but not statistically significantly different from the 2.7% rate with 12 months of DAPT.
Dr. Kim noted that the study had several limitations: It was open label, had no placebo control, and was underpowered to draw definite conclusions regarding the merits of dropping aspirin and continuing ticagrelor after 3 months in STEMI patients.
“Our findings should be interpreted with caution and call for confirmatory randomized trials,” he stressed.
Session comoderator Roxana Mehran, MD, said she “wholeheartedly” agrees with that assessment.
“We really do need a future trial, and we’re working to design TWILIGHT-STEMI,” a large randomized follow-up to the TWILIGHT trial, which she directed.
“I often imagine that we can have an even shorter duration of aspirin and ticagrelor and go to monotherapy sooner than 3 months in this very, very important subgroup,” added Dr. Mehran, professor of medicine, professor of population science and policy, and director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai, New York.
Discussant Marco Valgimigli, MD, PhD, of University Hospital in Bern, Switzerland, calculated that the number-needed-to-treat with ticagrelor monotherapy rather than 12 months of DAPT in order to prevent one additional major bleeding event in TICO-STEMI participants at high bleeding risk was 22, as compared to an NNT of 77 in those without high bleeding risk.
“From a clinical standpoint, this strategy seems particularly appealing in high bleeding risk patients,” the cardiologist concluded at the at the meeting, which was sponsored by the Cardiovascular Research Foundation.
He added, however, that the TICO-STEMI data with respect to complex PCI “are not really reassuring and are probably worth another investigation.”
Dr. Kim reported having no financial conflicts regarding the TICO-STEMI trial, funded by Biotronik.
, a major randomized trial.
“This is the first report assessing the feasibility of ticagrelor monotherapy after short-term DAPT for STEMI patients with drug-eluting stents,” Byeong-Keuk Kim, MD, PhD, noted at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
The positive results were consistent with the earlier TWILIGHT study (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention), which also showed clinical benefit at 1 year for 3 months of DAPT followed by ticagrelor (Brilinta) monotherapy, albeit only in PCI patients without an acute coronary syndrome (ACS) or with non-STEMI ACS (N Engl J Med. 2019 Nov 21;381[21]:2032-42).
TICO-STEMI was a prespecified substudy involving the 1,103 STEMI patients included in the previously reported parent 38-center South Korean TICO (Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI) study of 3,056 ACS patients treated with a second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stent (JAMA. 2020 Jun 16;323[23]:2407-16).
The primary outcome in TICO-STEMI was the 12-month composite rate of net adverse clinical events, composed of major bleeding, all-cause mortality, acute MI, stroke, stent thrombosis, or target vessel revascularization. In an intention-to-treat analysis, the rate was 5.0% in the 12-month DAPT group and 3.7% with ticagrelor monotherapy after 3 months of DAPT, for a 27% relative risk reduction which didn’t achieve statistical significance. However, in an as-treated analysis, the between-group difference in the primary endpoint was stronger: a 5.2% incidence with 12 months of DAPT and 2.3% with ticagrelor monotherapy, for a relative risk reduction of 56%, which was statistically significant.
Major bleeding, one of two key secondary endpoints, was a different story: The incidence within 12 months by intention-to-treat was 2.9% with 12 months of DAPT compared to 0.9% with ticagrelor monotherapy, for a statistically significant 68% relative risk reduction in favor of ticagrelor monotherapy. In contrast, there was no between-group difference in the other secondary endpoint composed of major adverse cardio- and cerebrovascular events: 2.7% with ticagrelor monotherapy, 2.5% with 12 months of DAPT.
In the subgroup of TICO-STEMI patients at high bleeding risk, ticagrelor monotherapy was associated with a 12-month major bleeding rate of 1.8%, compared to 6.3% with a full year of DAPT. Conversely, in patients who underwent complex PCI, ticagrelor monotherapy was associated with a 4.9% rate of major adverse cardio- and cerebrovascular events through 1 year, numerically greater than but not statistically significantly different from the 2.7% rate with 12 months of DAPT.
Dr. Kim noted that the study had several limitations: It was open label, had no placebo control, and was underpowered to draw definite conclusions regarding the merits of dropping aspirin and continuing ticagrelor after 3 months in STEMI patients.
“Our findings should be interpreted with caution and call for confirmatory randomized trials,” he stressed.
Session comoderator Roxana Mehran, MD, said she “wholeheartedly” agrees with that assessment.
“We really do need a future trial, and we’re working to design TWILIGHT-STEMI,” a large randomized follow-up to the TWILIGHT trial, which she directed.
“I often imagine that we can have an even shorter duration of aspirin and ticagrelor and go to monotherapy sooner than 3 months in this very, very important subgroup,” added Dr. Mehran, professor of medicine, professor of population science and policy, and director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai, New York.
Discussant Marco Valgimigli, MD, PhD, of University Hospital in Bern, Switzerland, calculated that the number-needed-to-treat with ticagrelor monotherapy rather than 12 months of DAPT in order to prevent one additional major bleeding event in TICO-STEMI participants at high bleeding risk was 22, as compared to an NNT of 77 in those without high bleeding risk.
“From a clinical standpoint, this strategy seems particularly appealing in high bleeding risk patients,” the cardiologist concluded at the at the meeting, which was sponsored by the Cardiovascular Research Foundation.
He added, however, that the TICO-STEMI data with respect to complex PCI “are not really reassuring and are probably worth another investigation.”
Dr. Kim reported having no financial conflicts regarding the TICO-STEMI trial, funded by Biotronik.
, a major randomized trial.
“This is the first report assessing the feasibility of ticagrelor monotherapy after short-term DAPT for STEMI patients with drug-eluting stents,” Byeong-Keuk Kim, MD, PhD, noted at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
The positive results were consistent with the earlier TWILIGHT study (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention), which also showed clinical benefit at 1 year for 3 months of DAPT followed by ticagrelor (Brilinta) monotherapy, albeit only in PCI patients without an acute coronary syndrome (ACS) or with non-STEMI ACS (N Engl J Med. 2019 Nov 21;381[21]:2032-42).
TICO-STEMI was a prespecified substudy involving the 1,103 STEMI patients included in the previously reported parent 38-center South Korean TICO (Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI) study of 3,056 ACS patients treated with a second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stent (JAMA. 2020 Jun 16;323[23]:2407-16).
The primary outcome in TICO-STEMI was the 12-month composite rate of net adverse clinical events, composed of major bleeding, all-cause mortality, acute MI, stroke, stent thrombosis, or target vessel revascularization. In an intention-to-treat analysis, the rate was 5.0% in the 12-month DAPT group and 3.7% with ticagrelor monotherapy after 3 months of DAPT, for a 27% relative risk reduction which didn’t achieve statistical significance. However, in an as-treated analysis, the between-group difference in the primary endpoint was stronger: a 5.2% incidence with 12 months of DAPT and 2.3% with ticagrelor monotherapy, for a relative risk reduction of 56%, which was statistically significant.
Major bleeding, one of two key secondary endpoints, was a different story: The incidence within 12 months by intention-to-treat was 2.9% with 12 months of DAPT compared to 0.9% with ticagrelor monotherapy, for a statistically significant 68% relative risk reduction in favor of ticagrelor monotherapy. In contrast, there was no between-group difference in the other secondary endpoint composed of major adverse cardio- and cerebrovascular events: 2.7% with ticagrelor monotherapy, 2.5% with 12 months of DAPT.
In the subgroup of TICO-STEMI patients at high bleeding risk, ticagrelor monotherapy was associated with a 12-month major bleeding rate of 1.8%, compared to 6.3% with a full year of DAPT. Conversely, in patients who underwent complex PCI, ticagrelor monotherapy was associated with a 4.9% rate of major adverse cardio- and cerebrovascular events through 1 year, numerically greater than but not statistically significantly different from the 2.7% rate with 12 months of DAPT.
Dr. Kim noted that the study had several limitations: It was open label, had no placebo control, and was underpowered to draw definite conclusions regarding the merits of dropping aspirin and continuing ticagrelor after 3 months in STEMI patients.
“Our findings should be interpreted with caution and call for confirmatory randomized trials,” he stressed.
Session comoderator Roxana Mehran, MD, said she “wholeheartedly” agrees with that assessment.
“We really do need a future trial, and we’re working to design TWILIGHT-STEMI,” a large randomized follow-up to the TWILIGHT trial, which she directed.
“I often imagine that we can have an even shorter duration of aspirin and ticagrelor and go to monotherapy sooner than 3 months in this very, very important subgroup,” added Dr. Mehran, professor of medicine, professor of population science and policy, and director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai, New York.
Discussant Marco Valgimigli, MD, PhD, of University Hospital in Bern, Switzerland, calculated that the number-needed-to-treat with ticagrelor monotherapy rather than 12 months of DAPT in order to prevent one additional major bleeding event in TICO-STEMI participants at high bleeding risk was 22, as compared to an NNT of 77 in those without high bleeding risk.
“From a clinical standpoint, this strategy seems particularly appealing in high bleeding risk patients,” the cardiologist concluded at the at the meeting, which was sponsored by the Cardiovascular Research Foundation.
He added, however, that the TICO-STEMI data with respect to complex PCI “are not really reassuring and are probably worth another investigation.”
Dr. Kim reported having no financial conflicts regarding the TICO-STEMI trial, funded by Biotronik.
AT TCT 2020
Choose wisely
Four years ago, just prior to the 2016 presidential election, I mentioned the Choosing Wisely campaign in my JFP editorial.1 I said that family physicians should do their part in controlling health care costs by carefully selecting tests and treatments that are known to be effective and avoiding those that are not. This remains as true now as it was then.
The Choosing Wisely campaign was sparked by a family physician, Dr. Howard Brody, in the context of national health care reform. In a 2010 New England Journal of Medicine editorial, he challenged physicians to do their part in controlling health care costs by not ordering tests and treatments that have no value for patients.2 At that time, it was estimated that a third of tests and treatments ordered by US physicians were of marginal or no value.3
Dr. Brody’s editorial caught the attention of the National Physicians Alliance and eventually many other physician organizations. In 2012, the American Board of Internal Medicine Foundation launched the Choosing Wisely initiative; today, the campaign Web site, choosingwisely.org, has a wealth of information and practice recommendations from 78 medical specialty organizations, including the American Academy of Family Physicians (AAFP).
In this month’s issue of JFP, Dr. Kate Rowland has summarized 10 of the most important Choosing Wisely recommendations that apply to family physicians and other primary care clinicians. Here are 5 more recommendations from the Choosing Wisely list of tests and treatments to avoid ordering for your patients:
- Don’t perform pelvic exams on asymptomatic nonpregnant women, unless necessary for guideline-appropriate screening for cervical cancer.
- Don’t routinely screen for prostate cancer using a prostate-specific antigen (PSA) test or digital rectal exam. For men who want PSA screening, it should be performed only after engaging in shared decision-making.
- Don’t order annual electrocardiograms or any other cardiac screening for low-risk patients without symptoms.
- Don’t routinely prescribe antibiotics for otitis media in children ages 2 to 12 years with nonsevere symptoms when observation is reasonable.
- Don’t use dual-energy x-ray absorptiometry screening for osteoporosis in women younger than 65 or men younger than 70 with no risk factors.
In total, AAFP lists 18 recommendations (2 additional recommendations have been withdrawn, based on updated evidence) on the Choosing Wisely Web site. I encourage you to review them to see if you should change any of your current patient recommendations.
1. Hickner J. Count on this no matter who wins the election. J Fam Pract. 2016;65:664.
2. Brody H. Medicine’s ethical responsibility for health care reform—the Top Five list. N Engl J Med. 2010;362:283-285.
3. Fisher ES, Bynum JP, Skinner JS. Slowing the growth of health care costs—lessons from regional variation. N Engl J Med. 2009;360:849-852.
Editor-in-Chief
Editor-in-Chief
Editor-in-Chief
Four years ago, just prior to the 2016 presidential election, I mentioned the Choosing Wisely campaign in my JFP editorial.1 I said that family physicians should do their part in controlling health care costs by carefully selecting tests and treatments that are known to be effective and avoiding those that are not. This remains as true now as it was then.
The Choosing Wisely campaign was sparked by a family physician, Dr. Howard Brody, in the context of national health care reform. In a 2010 New England Journal of Medicine editorial, he challenged physicians to do their part in controlling health care costs by not ordering tests and treatments that have no value for patients.2 At that time, it was estimated that a third of tests and treatments ordered by US physicians were of marginal or no value.3
Dr. Brody’s editorial caught the attention of the National Physicians Alliance and eventually many other physician organizations. In 2012, the American Board of Internal Medicine Foundation launched the Choosing Wisely initiative; today, the campaign Web site, choosingwisely.org, has a wealth of information and practice recommendations from 78 medical specialty organizations, including the American Academy of Family Physicians (AAFP).
In this month’s issue of JFP, Dr. Kate Rowland has summarized 10 of the most important Choosing Wisely recommendations that apply to family physicians and other primary care clinicians. Here are 5 more recommendations from the Choosing Wisely list of tests and treatments to avoid ordering for your patients:
- Don’t perform pelvic exams on asymptomatic nonpregnant women, unless necessary for guideline-appropriate screening for cervical cancer.
- Don’t routinely screen for prostate cancer using a prostate-specific antigen (PSA) test or digital rectal exam. For men who want PSA screening, it should be performed only after engaging in shared decision-making.
- Don’t order annual electrocardiograms or any other cardiac screening for low-risk patients without symptoms.
- Don’t routinely prescribe antibiotics for otitis media in children ages 2 to 12 years with nonsevere symptoms when observation is reasonable.
- Don’t use dual-energy x-ray absorptiometry screening for osteoporosis in women younger than 65 or men younger than 70 with no risk factors.
In total, AAFP lists 18 recommendations (2 additional recommendations have been withdrawn, based on updated evidence) on the Choosing Wisely Web site. I encourage you to review them to see if you should change any of your current patient recommendations.
Four years ago, just prior to the 2016 presidential election, I mentioned the Choosing Wisely campaign in my JFP editorial.1 I said that family physicians should do their part in controlling health care costs by carefully selecting tests and treatments that are known to be effective and avoiding those that are not. This remains as true now as it was then.
The Choosing Wisely campaign was sparked by a family physician, Dr. Howard Brody, in the context of national health care reform. In a 2010 New England Journal of Medicine editorial, he challenged physicians to do their part in controlling health care costs by not ordering tests and treatments that have no value for patients.2 At that time, it was estimated that a third of tests and treatments ordered by US physicians were of marginal or no value.3
Dr. Brody’s editorial caught the attention of the National Physicians Alliance and eventually many other physician organizations. In 2012, the American Board of Internal Medicine Foundation launched the Choosing Wisely initiative; today, the campaign Web site, choosingwisely.org, has a wealth of information and practice recommendations from 78 medical specialty organizations, including the American Academy of Family Physicians (AAFP).
In this month’s issue of JFP, Dr. Kate Rowland has summarized 10 of the most important Choosing Wisely recommendations that apply to family physicians and other primary care clinicians. Here are 5 more recommendations from the Choosing Wisely list of tests and treatments to avoid ordering for your patients:
- Don’t perform pelvic exams on asymptomatic nonpregnant women, unless necessary for guideline-appropriate screening for cervical cancer.
- Don’t routinely screen for prostate cancer using a prostate-specific antigen (PSA) test or digital rectal exam. For men who want PSA screening, it should be performed only after engaging in shared decision-making.
- Don’t order annual electrocardiograms or any other cardiac screening for low-risk patients without symptoms.
- Don’t routinely prescribe antibiotics for otitis media in children ages 2 to 12 years with nonsevere symptoms when observation is reasonable.
- Don’t use dual-energy x-ray absorptiometry screening for osteoporosis in women younger than 65 or men younger than 70 with no risk factors.
In total, AAFP lists 18 recommendations (2 additional recommendations have been withdrawn, based on updated evidence) on the Choosing Wisely Web site. I encourage you to review them to see if you should change any of your current patient recommendations.
1. Hickner J. Count on this no matter who wins the election. J Fam Pract. 2016;65:664.
2. Brody H. Medicine’s ethical responsibility for health care reform—the Top Five list. N Engl J Med. 2010;362:283-285.
3. Fisher ES, Bynum JP, Skinner JS. Slowing the growth of health care costs—lessons from regional variation. N Engl J Med. 2009;360:849-852.
1. Hickner J. Count on this no matter who wins the election. J Fam Pract. 2016;65:664.
2. Brody H. Medicine’s ethical responsibility for health care reform—the Top Five list. N Engl J Med. 2010;362:283-285.
3. Fisher ES, Bynum JP, Skinner JS. Slowing the growth of health care costs—lessons from regional variation. N Engl J Med. 2009;360:849-852.
Female cardiac advantage essentially lost after MI
Women are known to lag 5-10 years behind men in experiencing coronary heart disease (CHD), but new research suggests the gap narrows substantially following a myocardial infarction.
“Women lose a considerable portion, but not all, of their coronary and survival advantage – i.e., the lower event rates – after suffering a MI,” study author Sanne Peters, PhD, George Institute for Global Health, Imperial College London, said in an interview.
Previous studies of sex differences in event rates after a coronary event have produced mixed results and were primarily focused on mortality following MI. Importantly, the studies also lacked a control group without a history of CHD and, thus, were unable to provide a reference point for the disparity in event rates, she explained.
Using the MarketScan and Medicare databases, however, Dr. Peters and colleagues matched 339,890 U.S. adults hospitalized for an MI between January 2015 and December 2016 with 1,359,560 U.S. adults without a history of CHD.
Over a median 1.3 years follow-up, there were 12,518 MIs in the non-CHD group and 27,115 recurrent MIs in the MI group.
The age-standardized rate of MI per 1,000 person-years was 4.0 in women and 6.1 in men without a history of CHD, compared with 57.6 in women and 62.7 in men with a prior MI.
After multivariate adjustment, the women-to-men hazard ratio for MI was 0.64 (95% confidence interval, 0.62-0.67) in the non-CHD group and 0.94 (95% CI, 0.92-0.96) in the prior MI group, the authors reported Oct. 5 in the Journal of the American College of Cardiology
Additional results show the multivariate adjusted women-to-men hazard ratios for three other cardiovascular outcomes follow a similar pattern in the non-CHD and prior MI groups:
- CHD events: 0.53 (95% CI, 0.51-0.54) and 0.87 (95% CI, 0.85-0.89).
- Heart failure hospitalization: 0.93 (95% CI, 0.90-0.96) and 1.02 (95% CI, 1.00-1.04).
- All-cause mortality: 0.72 (95% CI, 0.71-0.73) and 0.90 (95% CI, 0.89-0.92).
“By including a control group of individuals without CHD, we demonstrated that the magnitude of the sex difference in cardiac event rates and survival is considerably smaller among those with prior MI than among those without a history of CHD,” Dr. Peters said.
Of note, the sex differences were consistent across age and race/ethnicity groups for all events, except for heart failure hospitalizations, where the adjusted hazard ratio for women vs. men age 80 years or older was 0.95 for those without a history of CHD (95% CI, 0.91-0.98) and 0.99 (95% CI, 0.96-1.02) for participants with a previous MI.
Dr. Peters said it’s not clear why the female advantage is attenuated post-MI but that one explanation is that women are less likely than men to receive guideline-recommended treatments and dosages or to adhere to prescribed therapies after MI hospitalization, which could put them at a higher risk of subsequent events and worse outcomes than men.
“Sex differences in pathophysiology of CHD and its complications may also explain, to some extent, why the rates of recurrent events are considerably more similar between the sexes than incident event rates,” she said. Compared with men, women have a higher incidence of MI with nonobstructive coronary artery disease and of heart failure with preserved ejection fraction, and evidence-based treatment options are more limited for both conditions.
“After people read this, I think the important thing to recognize is we need to push– as much as we can, with what meds we have, and what data we have – secondary prevention in these women,” Laxmi Mehta, MD, director of preventive cardiology and women’s cardiovascular health at Ohio State University, Columbus, said in an interview.
The lack of a female advantage post-MI should also elicit a “really meaningful conversation with our patients on shared decision-making of why they need to be on medications, remembering on our part to prescribe the medications, remembering to prescribe cardiac rehab, and also reminding our community we do need more data and need to investigate this further,” she said.
In an accompanying editorial, Nanette Wenger, MD, of Emory University, Atlanta, also points out that nonobstructive coronary disease is more common in women and, “yet, guideline-based therapies are those validated for obstructive coronary disease in a predominantly male population but, nonetheless, are applied for nonobstructive coronary disease.”
She advocates for aggressive evaluation and treatment for women with chest pain symptoms as well as early identification of women at risk for CHD, specifically those with metabolic syndrome, preeclampsia, hypertensive disorders of pregnancy, chronic inflammatory conditions, and high-risk race/ethnicity.
“Next, when coronary angiography is undertaken, particularly in younger women, an assiduous search for spontaneous coronary artery dissection and its appropriate management, as well as prompt and evidence-based interventions and medical therapies for an acute coronary event [are indicated],” Dr. Wenger wrote. “However, basic to improving outcomes for women is the elucidation of the optimal noninvasive techniques to identify microvascular disease, which could then enable delineation of appropriate preventive and therapeutic approaches.”
Dr. Peters is supported by a U.K. Medical Research Council Skills Development Fellowship. Dr. Mehta and Dr. Wenger disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Women are known to lag 5-10 years behind men in experiencing coronary heart disease (CHD), but new research suggests the gap narrows substantially following a myocardial infarction.
“Women lose a considerable portion, but not all, of their coronary and survival advantage – i.e., the lower event rates – after suffering a MI,” study author Sanne Peters, PhD, George Institute for Global Health, Imperial College London, said in an interview.
Previous studies of sex differences in event rates after a coronary event have produced mixed results and were primarily focused on mortality following MI. Importantly, the studies also lacked a control group without a history of CHD and, thus, were unable to provide a reference point for the disparity in event rates, she explained.
Using the MarketScan and Medicare databases, however, Dr. Peters and colleagues matched 339,890 U.S. adults hospitalized for an MI between January 2015 and December 2016 with 1,359,560 U.S. adults without a history of CHD.
Over a median 1.3 years follow-up, there were 12,518 MIs in the non-CHD group and 27,115 recurrent MIs in the MI group.
The age-standardized rate of MI per 1,000 person-years was 4.0 in women and 6.1 in men without a history of CHD, compared with 57.6 in women and 62.7 in men with a prior MI.
After multivariate adjustment, the women-to-men hazard ratio for MI was 0.64 (95% confidence interval, 0.62-0.67) in the non-CHD group and 0.94 (95% CI, 0.92-0.96) in the prior MI group, the authors reported Oct. 5 in the Journal of the American College of Cardiology
Additional results show the multivariate adjusted women-to-men hazard ratios for three other cardiovascular outcomes follow a similar pattern in the non-CHD and prior MI groups:
- CHD events: 0.53 (95% CI, 0.51-0.54) and 0.87 (95% CI, 0.85-0.89).
- Heart failure hospitalization: 0.93 (95% CI, 0.90-0.96) and 1.02 (95% CI, 1.00-1.04).
- All-cause mortality: 0.72 (95% CI, 0.71-0.73) and 0.90 (95% CI, 0.89-0.92).
“By including a control group of individuals without CHD, we demonstrated that the magnitude of the sex difference in cardiac event rates and survival is considerably smaller among those with prior MI than among those without a history of CHD,” Dr. Peters said.
Of note, the sex differences were consistent across age and race/ethnicity groups for all events, except for heart failure hospitalizations, where the adjusted hazard ratio for women vs. men age 80 years or older was 0.95 for those without a history of CHD (95% CI, 0.91-0.98) and 0.99 (95% CI, 0.96-1.02) for participants with a previous MI.
Dr. Peters said it’s not clear why the female advantage is attenuated post-MI but that one explanation is that women are less likely than men to receive guideline-recommended treatments and dosages or to adhere to prescribed therapies after MI hospitalization, which could put them at a higher risk of subsequent events and worse outcomes than men.
“Sex differences in pathophysiology of CHD and its complications may also explain, to some extent, why the rates of recurrent events are considerably more similar between the sexes than incident event rates,” she said. Compared with men, women have a higher incidence of MI with nonobstructive coronary artery disease and of heart failure with preserved ejection fraction, and evidence-based treatment options are more limited for both conditions.
“After people read this, I think the important thing to recognize is we need to push– as much as we can, with what meds we have, and what data we have – secondary prevention in these women,” Laxmi Mehta, MD, director of preventive cardiology and women’s cardiovascular health at Ohio State University, Columbus, said in an interview.
The lack of a female advantage post-MI should also elicit a “really meaningful conversation with our patients on shared decision-making of why they need to be on medications, remembering on our part to prescribe the medications, remembering to prescribe cardiac rehab, and also reminding our community we do need more data and need to investigate this further,” she said.
In an accompanying editorial, Nanette Wenger, MD, of Emory University, Atlanta, also points out that nonobstructive coronary disease is more common in women and, “yet, guideline-based therapies are those validated for obstructive coronary disease in a predominantly male population but, nonetheless, are applied for nonobstructive coronary disease.”
She advocates for aggressive evaluation and treatment for women with chest pain symptoms as well as early identification of women at risk for CHD, specifically those with metabolic syndrome, preeclampsia, hypertensive disorders of pregnancy, chronic inflammatory conditions, and high-risk race/ethnicity.
“Next, when coronary angiography is undertaken, particularly in younger women, an assiduous search for spontaneous coronary artery dissection and its appropriate management, as well as prompt and evidence-based interventions and medical therapies for an acute coronary event [are indicated],” Dr. Wenger wrote. “However, basic to improving outcomes for women is the elucidation of the optimal noninvasive techniques to identify microvascular disease, which could then enable delineation of appropriate preventive and therapeutic approaches.”
Dr. Peters is supported by a U.K. Medical Research Council Skills Development Fellowship. Dr. Mehta and Dr. Wenger disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Women are known to lag 5-10 years behind men in experiencing coronary heart disease (CHD), but new research suggests the gap narrows substantially following a myocardial infarction.
“Women lose a considerable portion, but not all, of their coronary and survival advantage – i.e., the lower event rates – after suffering a MI,” study author Sanne Peters, PhD, George Institute for Global Health, Imperial College London, said in an interview.
Previous studies of sex differences in event rates after a coronary event have produced mixed results and were primarily focused on mortality following MI. Importantly, the studies also lacked a control group without a history of CHD and, thus, were unable to provide a reference point for the disparity in event rates, she explained.
Using the MarketScan and Medicare databases, however, Dr. Peters and colleagues matched 339,890 U.S. adults hospitalized for an MI between January 2015 and December 2016 with 1,359,560 U.S. adults without a history of CHD.
Over a median 1.3 years follow-up, there were 12,518 MIs in the non-CHD group and 27,115 recurrent MIs in the MI group.
The age-standardized rate of MI per 1,000 person-years was 4.0 in women and 6.1 in men without a history of CHD, compared with 57.6 in women and 62.7 in men with a prior MI.
After multivariate adjustment, the women-to-men hazard ratio for MI was 0.64 (95% confidence interval, 0.62-0.67) in the non-CHD group and 0.94 (95% CI, 0.92-0.96) in the prior MI group, the authors reported Oct. 5 in the Journal of the American College of Cardiology
Additional results show the multivariate adjusted women-to-men hazard ratios for three other cardiovascular outcomes follow a similar pattern in the non-CHD and prior MI groups:
- CHD events: 0.53 (95% CI, 0.51-0.54) and 0.87 (95% CI, 0.85-0.89).
- Heart failure hospitalization: 0.93 (95% CI, 0.90-0.96) and 1.02 (95% CI, 1.00-1.04).
- All-cause mortality: 0.72 (95% CI, 0.71-0.73) and 0.90 (95% CI, 0.89-0.92).
“By including a control group of individuals without CHD, we demonstrated that the magnitude of the sex difference in cardiac event rates and survival is considerably smaller among those with prior MI than among those without a history of CHD,” Dr. Peters said.
Of note, the sex differences were consistent across age and race/ethnicity groups for all events, except for heart failure hospitalizations, where the adjusted hazard ratio for women vs. men age 80 years or older was 0.95 for those without a history of CHD (95% CI, 0.91-0.98) and 0.99 (95% CI, 0.96-1.02) for participants with a previous MI.
Dr. Peters said it’s not clear why the female advantage is attenuated post-MI but that one explanation is that women are less likely than men to receive guideline-recommended treatments and dosages or to adhere to prescribed therapies after MI hospitalization, which could put them at a higher risk of subsequent events and worse outcomes than men.
“Sex differences in pathophysiology of CHD and its complications may also explain, to some extent, why the rates of recurrent events are considerably more similar between the sexes than incident event rates,” she said. Compared with men, women have a higher incidence of MI with nonobstructive coronary artery disease and of heart failure with preserved ejection fraction, and evidence-based treatment options are more limited for both conditions.
“After people read this, I think the important thing to recognize is we need to push– as much as we can, with what meds we have, and what data we have – secondary prevention in these women,” Laxmi Mehta, MD, director of preventive cardiology and women’s cardiovascular health at Ohio State University, Columbus, said in an interview.
The lack of a female advantage post-MI should also elicit a “really meaningful conversation with our patients on shared decision-making of why they need to be on medications, remembering on our part to prescribe the medications, remembering to prescribe cardiac rehab, and also reminding our community we do need more data and need to investigate this further,” she said.
In an accompanying editorial, Nanette Wenger, MD, of Emory University, Atlanta, also points out that nonobstructive coronary disease is more common in women and, “yet, guideline-based therapies are those validated for obstructive coronary disease in a predominantly male population but, nonetheless, are applied for nonobstructive coronary disease.”
She advocates for aggressive evaluation and treatment for women with chest pain symptoms as well as early identification of women at risk for CHD, specifically those with metabolic syndrome, preeclampsia, hypertensive disorders of pregnancy, chronic inflammatory conditions, and high-risk race/ethnicity.
“Next, when coronary angiography is undertaken, particularly in younger women, an assiduous search for spontaneous coronary artery dissection and its appropriate management, as well as prompt and evidence-based interventions and medical therapies for an acute coronary event [are indicated],” Dr. Wenger wrote. “However, basic to improving outcomes for women is the elucidation of the optimal noninvasive techniques to identify microvascular disease, which could then enable delineation of appropriate preventive and therapeutic approaches.”
Dr. Peters is supported by a U.K. Medical Research Council Skills Development Fellowship. Dr. Mehta and Dr. Wenger disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
T2D treatments create tension between glycemic and cardiovascular goals
It was no surprise that updated guidelines recently published by the European Society of Cardiology for managing cardiovascular disease in patients with diabetes highlighted optimized treatment from a cardiovascular disease perspective, while a nearly concurrent update from two major diabetes societies saw the same issue from a more glycemic point of view.
This difference led to divergent approaches to managing hyperglycemia in patients with type 2 diabetes (T2D). The two diabetes societies that wrote one set of recommendations, the American Diabetes Association and the European Association for the Study of Diabetes, put metformin at the pinnacle of their drug hierarchy. Patients with T2D and established atherosclerotic cardiovascular disease (CVD), chronic kidney disease, or heart failure should all receive metformin first unless contraindicated or not tolerated, their updated consensus report said.
Once metformin is on board, a clinician can then add a second diabetes agent from among the two drug classes recently proven to also reduce cardiovascular and renal events, either the SGLT2 (sodium-glucose transporter 2) inhibitors, or GLP-1 (glucagonlike peptide–1) receptor agonists, they advised.
Cardiovascular disease focus represents a ‘major paradigm shift’
In contrast, the ESC guidelines called for upfront, systematic assessment of CVD risk in patients with T2D before treatment starts, and for patients in high- or very high–risk strata, the guidelines recommended starting the patient first on an SGLT2 inhibitor or a GLP-1 receptor agonist, and only adding metformin in patients who need additional glycemic control.
The guidelines also recommended starting treatment-naive patients with moderate CVD risk on metformin. For patients already on metformin, the new ESC guidelines called for adding an agent from at least one of these two drug classes with proven CVD benefits for those at high or very high CVD risk. The guidelines also note that the CVD benefits of the two newer drug classes differ and hence require further individualization depending on the risks faced by each patient, such as the risk for heart failure hospitalizations.
It’s an approach “driven by data from the cardiovascular outcome trials,” that showed several drugs from both the SGLT2 inhibitor and GLP-1 receptor agonist classes have substantial benefit for preventing cardiovascular events, renal events, hospitalizations for heart failure, and in some studies all-cause mortality, said Francesco Cosentino, MD, during a discussion of the guideline differences at the virtual annual meeting of the European Association for the Study of Diabetes.
The ESC approach also represents “a major paradigm shift,” a “change from a glucose-centric approach to an approach driven by cardiovascular disease events,” summed up Dr. Cosentino, professor of cardiology at the Karolinska Institute in Stockholm and chair of the task force that wrote the ESC’s 2019 updated guidelines. The ESC approach advocates initiating drugs for treating patients with T2D “based on cardiovascular disease risk classification,” he highlighted. Results from some SGLT2 inhibitor cardiovascular outcome trials showed that the CVD benefit was similar regardless of whether or not patients also received metformin.
ADA, EASD call for ‘a different emphasis’
“There is a different emphasis” in the statement issued by the diabetologists of the ADA and EASD, admitted Peter J. Grant, MD, a professor of diabetes and endocrinology at the University of Leeds (England) and cochair of the ESC guidelines task force. Dr. Grant represented the EASD on the task force, and the Association collaborated with the ESC in producing its guidelines.
“The ADA and EASD recommendations “look primarily at glucose control, with cardiovascular disease management as secondary.” In contrast, the ESC guidelines “are primarily cardiovascular disease risk guidelines, with a glucose interest,” Dr. Grant declared.
Despite his involvement in writing the ESC guidelines, Dr. Grant tilted toward the ADA/EASD statement as more globally relevant.
“There is much more to vasculopathy in diabetes than just macrovascular disease. Many patients with type 2 diabetes without macrovascular complications have microvascular disease,” including the potential for retinopathy, nephropathy, and neuropathy, he said. These complications can also have a strong impact on psychological well being and treatment satisfaction.
“It’s important that we’re not glucocentric any more, but it’s equally important that we treat glucose because it has such a benefit for microvascular disease.” Dr. Grant also cited metformin’s long history of safety and good tolerance, clinician comfort prescribing it, and its low price. Heavier reliance on SGLT2 inhibitors and GLP-1 receptor agonists will be expensive for the short term while the cost of these drugs remains high, which places a higher burden on “knowing we’re doing it right,” said Dr. Grant.
Dr. Cosentino pointed out that the higher cost of the drugs in the two classes shown to exert important cardiovascular and renal effects needs to be considered in a cost-effectiveness context, not just by cost alone.
‘Clinical inertia’ could be a danger
Dr. Cosentino played down a major disagreement between the two guidelines, suggesting that “focusing on the differences leads to clinical inertia” by the practicing community when they are unsure how to reconcile the two positions.
Dr. Grant agreed that adding a second drug to metformin right away made sense in at least selected patients. “Look at each patient and decide whether they need glycemic control. If so, and if they also have cardiovascular disease, use both drugs,” metformin, plus one agent from one of the two newer classes.
Something both experts agreed on is that it’s time to generally steer clear of sulfonylurea drugs. “We have evidence for harmful effects from sulfonylureas,” Dr. Cosentino said.
“I’d dump sulfonylureas,” was Dr. Grant’s assessment, but he added that they still have a role for patients who need additional glycemic control but can’t afford the newer drugs.
Dr. Cosentino has had financial relationships with Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Mundipharma, Novo Nordisk, and Pfizer, Dr. Grant has lectured on behalf of AstraZeneca, GlaxoSmithKline, Merck, Novo Nordisk, the Medicines Company, and Takeda, and he has been an adviser to Amgen, AstraZeneca, Novartis, Novo Nordisk, and Synexus.
It was no surprise that updated guidelines recently published by the European Society of Cardiology for managing cardiovascular disease in patients with diabetes highlighted optimized treatment from a cardiovascular disease perspective, while a nearly concurrent update from two major diabetes societies saw the same issue from a more glycemic point of view.
This difference led to divergent approaches to managing hyperglycemia in patients with type 2 diabetes (T2D). The two diabetes societies that wrote one set of recommendations, the American Diabetes Association and the European Association for the Study of Diabetes, put metformin at the pinnacle of their drug hierarchy. Patients with T2D and established atherosclerotic cardiovascular disease (CVD), chronic kidney disease, or heart failure should all receive metformin first unless contraindicated or not tolerated, their updated consensus report said.
Once metformin is on board, a clinician can then add a second diabetes agent from among the two drug classes recently proven to also reduce cardiovascular and renal events, either the SGLT2 (sodium-glucose transporter 2) inhibitors, or GLP-1 (glucagonlike peptide–1) receptor agonists, they advised.
Cardiovascular disease focus represents a ‘major paradigm shift’
In contrast, the ESC guidelines called for upfront, systematic assessment of CVD risk in patients with T2D before treatment starts, and for patients in high- or very high–risk strata, the guidelines recommended starting the patient first on an SGLT2 inhibitor or a GLP-1 receptor agonist, and only adding metformin in patients who need additional glycemic control.
The guidelines also recommended starting treatment-naive patients with moderate CVD risk on metformin. For patients already on metformin, the new ESC guidelines called for adding an agent from at least one of these two drug classes with proven CVD benefits for those at high or very high CVD risk. The guidelines also note that the CVD benefits of the two newer drug classes differ and hence require further individualization depending on the risks faced by each patient, such as the risk for heart failure hospitalizations.
It’s an approach “driven by data from the cardiovascular outcome trials,” that showed several drugs from both the SGLT2 inhibitor and GLP-1 receptor agonist classes have substantial benefit for preventing cardiovascular events, renal events, hospitalizations for heart failure, and in some studies all-cause mortality, said Francesco Cosentino, MD, during a discussion of the guideline differences at the virtual annual meeting of the European Association for the Study of Diabetes.
The ESC approach also represents “a major paradigm shift,” a “change from a glucose-centric approach to an approach driven by cardiovascular disease events,” summed up Dr. Cosentino, professor of cardiology at the Karolinska Institute in Stockholm and chair of the task force that wrote the ESC’s 2019 updated guidelines. The ESC approach advocates initiating drugs for treating patients with T2D “based on cardiovascular disease risk classification,” he highlighted. Results from some SGLT2 inhibitor cardiovascular outcome trials showed that the CVD benefit was similar regardless of whether or not patients also received metformin.
ADA, EASD call for ‘a different emphasis’
“There is a different emphasis” in the statement issued by the diabetologists of the ADA and EASD, admitted Peter J. Grant, MD, a professor of diabetes and endocrinology at the University of Leeds (England) and cochair of the ESC guidelines task force. Dr. Grant represented the EASD on the task force, and the Association collaborated with the ESC in producing its guidelines.
“The ADA and EASD recommendations “look primarily at glucose control, with cardiovascular disease management as secondary.” In contrast, the ESC guidelines “are primarily cardiovascular disease risk guidelines, with a glucose interest,” Dr. Grant declared.
Despite his involvement in writing the ESC guidelines, Dr. Grant tilted toward the ADA/EASD statement as more globally relevant.
“There is much more to vasculopathy in diabetes than just macrovascular disease. Many patients with type 2 diabetes without macrovascular complications have microvascular disease,” including the potential for retinopathy, nephropathy, and neuropathy, he said. These complications can also have a strong impact on psychological well being and treatment satisfaction.
“It’s important that we’re not glucocentric any more, but it’s equally important that we treat glucose because it has such a benefit for microvascular disease.” Dr. Grant also cited metformin’s long history of safety and good tolerance, clinician comfort prescribing it, and its low price. Heavier reliance on SGLT2 inhibitors and GLP-1 receptor agonists will be expensive for the short term while the cost of these drugs remains high, which places a higher burden on “knowing we’re doing it right,” said Dr. Grant.
Dr. Cosentino pointed out that the higher cost of the drugs in the two classes shown to exert important cardiovascular and renal effects needs to be considered in a cost-effectiveness context, not just by cost alone.
‘Clinical inertia’ could be a danger
Dr. Cosentino played down a major disagreement between the two guidelines, suggesting that “focusing on the differences leads to clinical inertia” by the practicing community when they are unsure how to reconcile the two positions.
Dr. Grant agreed that adding a second drug to metformin right away made sense in at least selected patients. “Look at each patient and decide whether they need glycemic control. If so, and if they also have cardiovascular disease, use both drugs,” metformin, plus one agent from one of the two newer classes.
Something both experts agreed on is that it’s time to generally steer clear of sulfonylurea drugs. “We have evidence for harmful effects from sulfonylureas,” Dr. Cosentino said.
“I’d dump sulfonylureas,” was Dr. Grant’s assessment, but he added that they still have a role for patients who need additional glycemic control but can’t afford the newer drugs.
Dr. Cosentino has had financial relationships with Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Mundipharma, Novo Nordisk, and Pfizer, Dr. Grant has lectured on behalf of AstraZeneca, GlaxoSmithKline, Merck, Novo Nordisk, the Medicines Company, and Takeda, and he has been an adviser to Amgen, AstraZeneca, Novartis, Novo Nordisk, and Synexus.
It was no surprise that updated guidelines recently published by the European Society of Cardiology for managing cardiovascular disease in patients with diabetes highlighted optimized treatment from a cardiovascular disease perspective, while a nearly concurrent update from two major diabetes societies saw the same issue from a more glycemic point of view.
This difference led to divergent approaches to managing hyperglycemia in patients with type 2 diabetes (T2D). The two diabetes societies that wrote one set of recommendations, the American Diabetes Association and the European Association for the Study of Diabetes, put metformin at the pinnacle of their drug hierarchy. Patients with T2D and established atherosclerotic cardiovascular disease (CVD), chronic kidney disease, or heart failure should all receive metformin first unless contraindicated or not tolerated, their updated consensus report said.
Once metformin is on board, a clinician can then add a second diabetes agent from among the two drug classes recently proven to also reduce cardiovascular and renal events, either the SGLT2 (sodium-glucose transporter 2) inhibitors, or GLP-1 (glucagonlike peptide–1) receptor agonists, they advised.
Cardiovascular disease focus represents a ‘major paradigm shift’
In contrast, the ESC guidelines called for upfront, systematic assessment of CVD risk in patients with T2D before treatment starts, and for patients in high- or very high–risk strata, the guidelines recommended starting the patient first on an SGLT2 inhibitor or a GLP-1 receptor agonist, and only adding metformin in patients who need additional glycemic control.
The guidelines also recommended starting treatment-naive patients with moderate CVD risk on metformin. For patients already on metformin, the new ESC guidelines called for adding an agent from at least one of these two drug classes with proven CVD benefits for those at high or very high CVD risk. The guidelines also note that the CVD benefits of the two newer drug classes differ and hence require further individualization depending on the risks faced by each patient, such as the risk for heart failure hospitalizations.
It’s an approach “driven by data from the cardiovascular outcome trials,” that showed several drugs from both the SGLT2 inhibitor and GLP-1 receptor agonist classes have substantial benefit for preventing cardiovascular events, renal events, hospitalizations for heart failure, and in some studies all-cause mortality, said Francesco Cosentino, MD, during a discussion of the guideline differences at the virtual annual meeting of the European Association for the Study of Diabetes.
The ESC approach also represents “a major paradigm shift,” a “change from a glucose-centric approach to an approach driven by cardiovascular disease events,” summed up Dr. Cosentino, professor of cardiology at the Karolinska Institute in Stockholm and chair of the task force that wrote the ESC’s 2019 updated guidelines. The ESC approach advocates initiating drugs for treating patients with T2D “based on cardiovascular disease risk classification,” he highlighted. Results from some SGLT2 inhibitor cardiovascular outcome trials showed that the CVD benefit was similar regardless of whether or not patients also received metformin.
ADA, EASD call for ‘a different emphasis’
“There is a different emphasis” in the statement issued by the diabetologists of the ADA and EASD, admitted Peter J. Grant, MD, a professor of diabetes and endocrinology at the University of Leeds (England) and cochair of the ESC guidelines task force. Dr. Grant represented the EASD on the task force, and the Association collaborated with the ESC in producing its guidelines.
“The ADA and EASD recommendations “look primarily at glucose control, with cardiovascular disease management as secondary.” In contrast, the ESC guidelines “are primarily cardiovascular disease risk guidelines, with a glucose interest,” Dr. Grant declared.
Despite his involvement in writing the ESC guidelines, Dr. Grant tilted toward the ADA/EASD statement as more globally relevant.
“There is much more to vasculopathy in diabetes than just macrovascular disease. Many patients with type 2 diabetes without macrovascular complications have microvascular disease,” including the potential for retinopathy, nephropathy, and neuropathy, he said. These complications can also have a strong impact on psychological well being and treatment satisfaction.
“It’s important that we’re not glucocentric any more, but it’s equally important that we treat glucose because it has such a benefit for microvascular disease.” Dr. Grant also cited metformin’s long history of safety and good tolerance, clinician comfort prescribing it, and its low price. Heavier reliance on SGLT2 inhibitors and GLP-1 receptor agonists will be expensive for the short term while the cost of these drugs remains high, which places a higher burden on “knowing we’re doing it right,” said Dr. Grant.
Dr. Cosentino pointed out that the higher cost of the drugs in the two classes shown to exert important cardiovascular and renal effects needs to be considered in a cost-effectiveness context, not just by cost alone.
‘Clinical inertia’ could be a danger
Dr. Cosentino played down a major disagreement between the two guidelines, suggesting that “focusing on the differences leads to clinical inertia” by the practicing community when they are unsure how to reconcile the two positions.
Dr. Grant agreed that adding a second drug to metformin right away made sense in at least selected patients. “Look at each patient and decide whether they need glycemic control. If so, and if they also have cardiovascular disease, use both drugs,” metformin, plus one agent from one of the two newer classes.
Something both experts agreed on is that it’s time to generally steer clear of sulfonylurea drugs. “We have evidence for harmful effects from sulfonylureas,” Dr. Cosentino said.
“I’d dump sulfonylureas,” was Dr. Grant’s assessment, but he added that they still have a role for patients who need additional glycemic control but can’t afford the newer drugs.
Dr. Cosentino has had financial relationships with Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Mundipharma, Novo Nordisk, and Pfizer, Dr. Grant has lectured on behalf of AstraZeneca, GlaxoSmithKline, Merck, Novo Nordisk, the Medicines Company, and Takeda, and he has been an adviser to Amgen, AstraZeneca, Novartis, Novo Nordisk, and Synexus.
FROM EASD 2020
Primary prevention of VTE spans a spectrum
Venous thromboembolism (VTE) is a common and dangerous disease, affecting 0.1%-0.2% of the population annually—a rate that might be underreported.1 VTE is a collective term for venous blood clots, including (1) deep vein thrombosis (DVT) of peripheral veins and (2) pulmonary embolism, which occurs after a clot travels through the heart and becomes lodged in the pulmonary vasculature. Two-thirds of VTE cases present clinically as DVT2; most mortality from VTE disease is caused by the 20% of cases of pulmonary embolism that present as sudden death.1
VTE is comparable to myocardial infarction (MI) in incidence and severity. In 2008, 208 of every 100,000 people had an MI, with a 30-day mortality of 16/100,0003; VTE disease has an annual incidence of 161 of every 100,000 people and a 28-day mortality of 18/100,000.4 Although the incidence and severity of MI are steadily decreasing, the rate of VTE appears constant.3,5 The high mortality of VTE suggests that primary prevention, which we discuss in this article, is valuable (see “Key points: Primary prevention of venous thromboembolism”).
SIDEBAR
Key points: Primary prevention of venous thromboembolism
- Primary prevention of venous thromboembolism (VTE), a disease with mortality similar to myocardial infarction, should be an important consideration in at-risk patients.
- Although statins reduce the risk of VTE, their use is justified only if they are also required for prevention of cardiovascular disease.
- The risk of travel-related VTE can be reduced by wearing compression stockings.
- The choice of particular methods of contraception and of hormone replacement therapy can reduce VTE risk.
- Because of the risk of bleeding, using anticoagulants for primary prevention of VTE is justified only in certain circumstances.
- Pregnancy is the only condition in which there is a guideline indication for thrombophilia testing, because test results in this setting can change recommendations for preventing VTE.
- Using a risk-stratification model is key to determining risk in both medically and surgically hospitalized patients. Trauma and major orthopedic surgery always place the patient at high risk of VTE.
Risk factors
Virchow’s triad of venous stasis, vascular injury, and hypercoagulability describes predisposing factors for VTE.6 Although venous valves promote blood flow, they produce isolated low-flow areas adjacent to valves that become concentrated and locally hypoxic, increasing the risk of clotting.7 The great majority of DVTs (≥ 96%) occur in the lower extremity,8 starting in the calf; there, 75% of cases resolve spontaneously before they extend into the deep veins of the proximal leg.7 One-half of DVTs that do move into the proximal leg eventually embolize.7
Major risk factors for VTE comprise inherited conditions, medical history, medical therapeutics, and behaviors (TABLE 1).9-11 Unlike the preventive management of coronary artery disease (CAD), there is no simple, generalized prevention algorithm to address VTE risk factors.
Risk factors for VTE and CAD overlap. Risk factors for atherosclerosis—obesity, diabetes, smoking, hypertension, hyperlipidemia—also increase the risk of VTE (TABLE 1).9-11 The association between risk factors for VTE and atherosclerosis is demonstrated by a doubling of the risk of MI and stroke in the year following VTE.11 Lifestyle changes are expected to reduce the risk of VTE, as they do for acute CAD, but studies are lacking to confirm this connection. There is no prospective evidence showing that weight loss or control of diabetes or hypertension reduces the risk of VTE.12 Smoking cessation does appear to reduce risk: Former smokers have the same VTE risk as never-smokers.13
Thrombophilia testing: Not generally useful
Inherited and acquired thrombophilic conditions define a group of disorders in which the risk of VTE is increased. Although thrombophilia testing was once considered for primary and secondary prevention of VTE, such testing is rarely used now because proof of benefit is lacking: A large case–control study showed that thrombophilia testing did not predict recurrence after a first VTE.14 Guidelines of the American College of Chest Physicians (ACCP) do not address thrombophilia, and the American Society of Hematology recommends against thrombophilia testing after a provoked VTE.15,16
Primary prophylaxis of patients with a family history of VTE and inherited thrombophilia is controversial. Patients with both a family history of VTE and demonstrated thrombophilia do have double the average incidence of VTE, but this increased risk does not offset the significant bleeding risk associated with anticoagulation.17 Recommendations for thrombophilia testing are limited to certain situations in pregnancy, discussed in a bit.16,18,19
Continue to: Primary prevention of VTE in the clinic
Primary prevention of VTE in the clinic
There is no single, overarching preventive strategy for VTE in an ambulatory patient (although statins, discussed in a moment, offer some benefit, broadly). There are, however, distinct behavioral characteristics and medical circumstances for which opportunities exist to reduce VTE risk—for example, when a person engages in long-distance travel, receives hormonal therapy, is pregnant, or has cancer. In each scenario, recognizing and mitigating risk are important.
Statins offer a (slight) benefit
There is evidence that statins reduce the risk of VTE—slightly20-23:
- A large randomized, controlled trial showed that rosuvastatin, 20 mg/d, reduced the rate of VTE, compared to placebo; however, the 2-year number needed to treat (NNT) was 349.20 The VTE benefit is minimal, however, compared to primary prevention of cardiovascular disease with statins (5-year NNT = 56).21 The sole significant adverse event associated with statins was new-onset type 2 diabetes (5-year number needed to harm = 235).21
- A subsequent meta-analysis confirmed a small reduction in VTE risk with statins.22 In its 2012 guidelines, ACCP declined to issue a recommendation on the use of statins for VTE prevention.23 When considering statins for primary cardiovascular disease prevention, take the additional VTE prevention into account.
Simple strategies can help prevent travel-related VTE
Travel is a common inciting factor for VTE. A systematic review showed that VTE risk triples after travel of ≥ 4 hours, increasing by 20% with each additional 2 hours.24 Most VTE occurs in travelers who have other VTE risk factors.25 Based on case–control studies,23 guidelines recommend these preventive measures:
- frequent calf exercises
- sitting in an aisle seat during air travel
- keeping hydrated.
A Cochrane review showed that graded compression stockings reduce asymptomatic DVT in travelers by a factor of 10, in high- and low-risk patients.26
VTE risk varies with type of hormonal contraception
Most contraceptives increase VTE risk (TABLE 227,28). Risk with combined oral contraceptives varies with the amount of estrogen and progesterone. To reduce VTE risk with oral contraceptives, patients can use an agent that contains a lower dose of estrogen or one in which levonorgestrel replaces other progesterones.27
Continue to: Studies suggest that the levonorgestrel-releasing...
Studies suggest that the levonorgestrel-releasing intrauterine device and progestin-only pills are not associated with an increase in VTE risk.27 Although the quality of evidence varies, most nonoral hormonal contraceptives have been determined to carry a risk of VTE that is similar to that of combined oral contraceptives.28
In hormone replacement, avoid pills to lower risk
Hormone replacement therapy (HRT) for postmenopausal women increases VTE risk when administered in oral form, with combined estrogen and progestin HRT doubling the risk and estrogen-only formulations having a lower risk.29 VTE risk is highest in the first 6 months of HRT, declining to that of a non-HRT user within 5 years.29 Neither transdermal HRT nor estrogen creams increase the risk of VTE, according to a systematic review.30 The estradiol-containing vaginal ring also does not confer increased risk.29
Pregnancy, thrombophilia, and VTE prevention
VTE affects as many as 0.2% of pregnancies but causes 9% of pregnancy-related deaths.18 The severity of VTE in pregnancy led the American College of Obstetricians and Gynecologists (ACOG) to recommend primary VTE prophylaxis in patients with certain thrombophilias.18 Thrombophilia testing is recommended in patients with proven high-risk thrombophilia in a first-degree relative.18 ACOG recognizes 5 thrombophilias considered to carry a high risk of VTE in pregnancy18:
- homozygous Factor V Leiden
- homozygous prothrombin G20210A mutation
- antithrombin deficiency
- heterozygous Factor V Leiden and prothrombin G20210A mutation
- antiphospholipid antibody syndrome.
ACOG recommends limiting thrombophilia testing to (1) any specific thrombophilia carried by a relative and (2) possibly, the antiphospholipid antibodies anticardiolipin and lupus anticoagulant.18,19 Antiphospholipid testing is recommended when there is a history of stillbirth, 3 early pregnancy losses, or delivery earlier than 34 weeks secondary to preeclampsia.19
Primary VTE prophylaxis is recommended for pregnant patients with a high-risk thrombophilia; low-molecular-weight heparin (LMWH) is safe and its effects are predictable.18 Because postpartum risk of VTE is higher than antepartum risk, postpartum prophylaxis is also recommended with lower-risk thrombophilias18; a vitamin K antagonist or LMWH can be used.18 ACCP and ACOG recommendations for VTE prophylaxis in pregnancy differ slightly (TABLE 316,18,19).
Continue to: Cancer increases risks of VTE and bleeding
Cancer increases risks of VTE and bleeding
Cancer increases VTE risk > 6-fold31; metastases, chemotherapy, and radiotherapy further increase risk. Cancer also greatly increases the risk of bleeding: Cancer patients with VTE have an annual major bleeding rate ≥ 20%.32 Guidelines do not recommend primary VTE prophylaxis for cancer, although American Society of Clinical Oncology guidelines discuss consideration of prophylaxis for select, high-risk patients,33,34 including those with multiple myeloma, metastatic gastrointestinal cancer, or metastatic brain cancer.31,34 Recent evidence (discussed in a moment) supports the use of apixaban for primary VTE prevention during chemotherapy for high-risk cancer.
The Khorana Risk Score (TABLE 435,36) for VTE was developed and validated for use in patients with solid cancer35: A score of 2 conveys nearly a 10% risk of VTE over 6 months.36 A recent study of 550 cancer patients with a Khorana score of ≥ 2—the first evidence of risk-guided primary VTE prevention in cancer—showed that primary prophylaxis with 2.5 mg of apixaban, bid, reduced the risk of VTE (NNT = 17); however, the number needed to harm (for major bleeding) was 59.37 Mortality was not changed with apixaban treatment
Primary VTE prevention in med-surg hospitalizations
The risk of VTE increases significantly during hospitalization, although not enough to justify universal prophylaxis. Recommended prevention strategies for different classes of hospitalized patients are summarized below.
In medically hospitalized patients, risk is stratified with a risk-assessment model. Medically hospitalized patients have, on average, a VTE risk of 1.2%23; 12 risk-assessment models designed to stratify risk were recently compared.38 Two models, the Caprini Score (TABLE 5)39 and the IMPROVE VTE Risk Calculator,40 were best able to identify low-risk patients (negative predictive value, > 99%).38 American Society of Hematology guidelines recommend IMPROVE VTE or the Padua Prediction Score for risk stratification.41 While the Caprini score only designates 11% of eventual VTE cases as low risk, both the IMPROVE VTE and Padua scores miss more than 35% of eventual VTE.38
Because LMWH prophylaxis has been shown to reduce VTE by 40% without increasing the risk of major bleeding, using Caprini should prevent 2 VTEs for every 1000 patients, without an increase in major bleeding and with 13 additional minor bleeding events.42
Continue to: Critically ill patients
Critically ill patients are assumed to be at high risk of VTE and do not require stratification.23 For high-risk patients, prophylaxis with LMWH, low-dose unfractionated heparin (LDUH), or fondaparinux is recommended for the duration of admission.23 For patients at high risk of both VTE and bleeding, mechanical prophylaxis with intermittent pneumatic compression (IPC) is recommended instead of LMWH, LDUH, or fondaparinux.23
Surgery, like trauma (see next page), increases the risk of VTE and has been well studied. Prophylaxis after orthopedic surgery differs from that of other types of surgery.
In orthopedic surgery, risk depends on the procedure. For major orthopedic surgery, including total hip or knee arthroplasty and hip fracture surgery, VTE prophylaxis is recommended for 35 days postsurgically.43 LMWH is the preferred agent, although many other means have been shown to be beneficial.44 A recent systematic review demonstrated that aspirin is not inferior to other medications after hip or knee arthroplasty.45 No mechanical or pharmacotherapeutic prophylaxis is generally recommended after nonmajor orthopedic surgery.43
Nonorthopedic surgery is stratified by risk factors, using Caprini44 (TABLE 539). For medium-risk patients (Caprini score, 3-4) LDUH, LMWH, or IPC is recommended; for high-risk patients (Caprini score, ≥ 5) preventive treatment should combine pharmacotherapeutic and mechanical prophylaxis.46 A recent meta-analysis, comprising 14,776 patients, showed that surgical patients with a Caprini score ≥ 7 had a reduced incidence of VTE when given chemoprophylaxis, whereas patients whose score is < 7 do not benefit from chemoprophylaxis.43 When bleeding risk is high, IPC is recommended as sole therapy.43 Prophylaxis is not recommended when risk (determined by the Caprini score) is low.46
Post-hospitalization. Risk of VTE can persist for as long as 90 days after hospitalization; this finding has led to evaluation of the benefit of prolonged chemoprophylaxis.23 Extended-duration LMWH prophylaxis decreases the incidence of VTE, but at the cost of increased risk of major bleeding.47 Based on this evidence, guidelines recommend against prolonged-duration anticoagulation.23 A 2016 trial showed that 35 days of the direct-acting anticoagulant betrixaban reduced the risk of symptomatic VTE events, compared to 10 days of LMWH (NNT = 167), without increased risk of bleeding.48 This is a limited benefit, however, that is unlikely to change guideline recommendations.
Continue to: Trauma
Trauma: VTE risk increases with severity
Trauma increases the risk of VTE considerably. A national study showed that 1.5% of admitted trauma patients experienced VTE during hospitalization and that 1.2% were readmitted for VTE within 1 year.49 As many as 32% of trauma patients admitted to the intensive care unit experience VTE despite appropriate prophylaxis.50 A Cochrane Review51 found that:
- prophylaxis significantly reduces DVT risk
- pharmacotherapeutic prophylaxis is more effective than mechanical prophylaxis
- LMWH is more effective than LDUH.
Guidelines recommend that major trauma patients receive prophylaxis with LMWH, LDUH, or IPC.46
CORRESPONDENCE
Michael J. Arnold, MD, CDR, MC, USN; Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Jacksonville, FL 32214; [email protected].
1. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010. 38(4 suppl):S495-S501.
2. Tagalakis V, Patenaude V, Kahn SR, et al. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE Study Cohort. Am J Med. 2013;126:832.e13-e21.
3. Yeh RW, Sidney S, Chandra M, et al. Population trends in the incidence and outcomes of acute myocardial infarction. N Engl J Med. 2010. 362:2155-2165.
4. Cushman M, Tsai AW, White RH, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med. 2004;117:19-25.
5. Goldhaber SZ. Venous thromboembolism: epidemiology and magnitude of the problem. Best Pract Res Clin Haematol. 2012;25:235-242.
6. Stone J, Hangge P, Albadawi H, et al. Deep vein thrombosis: pathogenesis, diagnosis, and medical management. Cardiovasc Diagn Ther. 2017;7(suppl 3):S276-S284.
7. Olaf M, Cooney R. Deep venous thrombosis. Emerg Med Clin North Am. 2017;35:743-770.
8. Sajid MS, Ahmed N, Desai M, et al. Upper limb deep vein thrombosis: a literature review to streamline the protocol for management. Acta Haematol. 2007;118:10-18.
9. Bates SM, Ginsberg JS. Clinical practice. Treatment of deep-vein thrombosis. N Engl J Med. 2004;351:268-277.
10. Chandra D, Parisini E, Mozaffarian D. Meta-analysis: travel and risk for venous thromboembolism. Ann Intern Med. 2009;151:180-190.
11. Goldhaber SZ. Risk factors for venous thromboembolism. J Am Col Cardiol. 2010;56:1-7.
12. Yang G, De Staercke C, Hooper WC. The effects of obesity on venous thromboembolism: a review. Open J Prev Med. 2012;2:499-509.
13. Severinsen MT, Kristensen SR, Johnsen SP, et al. Smoking and venous thromboembolism: a Danish follow-up study. J Thromb Haemost. 2009;7:1297-1303.
14. Coppens M, Reijnders JH, Middeldorp S, et al. Testing for inherited thrombophilia does not reduce the recurrence of venous thrombosis. J Thromb Haemost. 2008;6:1474-1477.
15. Choosing Wisely. American Society of Hematology. Ten things physicians and patients should question. www.choosingwisely.org/societies/american-society-of-hematology/. Accessed September 28, 2020.
16. Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e691S-e736S.
17. Vossen CY, Conard J, Fontcuberta J, et al. Risk of a first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prospective Cohort on Thrombophilia (EPCOT). J Thromb Haemost. 2005;3:459-464.
18. Practice Bulletin No. 197: Inherited thrombophilias in pregnancy. Obstet Gynecol. 2018;132:e18-e34.
19. Committee on Practice Bulletins—Obstetrics, American College of Obstetricians and Gynecologists. Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol. 2012;120:1514-1521.
20. Glynn RJ, Danielson E, Fonseca FAH, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med. 2009;360:1851-1861.
21. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013(1):CD004816.
22. Squizzato A, Galli M, Romualdi E, et al. Statins, fibrates, and venous thromboembolism: a meta-analysis. Eur Heart J. 2010;31:1248-1256.
23. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e195S-e226S.
24. Kelman CW, Kortt MA, Becker NG, et al. Deep vein thrombosis and air travel: record linkage study. BMJ. 2003;327:1072.
25. Johnston RV, Hudson MF; . Travelers’ thrombosis. Aviat Space Environ Med. 2014;85:191-194.
26. Clarke MJ, Broderick C, Hopewell S, et al. Compression stockings for preventing deep vein thrombosis in airline passengers. Cochrane Database Syst Rev. 2016;9:CD004002.
27. van Hylckama Vlieg A, Middledorp S. Hormone therapies and venous thromboembolism: where are we now? J Thromb Haemost. 2011;9:257-266.
28. Tepper NK, Dragoman MV, Gaffield ME, et al. Nonoral combined hormonal contraceptives and thromboembolism: a systematic review. Contraception. 2017;95:130-139.
29. Lekovic D, Miljic P, Dmitrovic A, et al. How do you decide on hormone replacement therapy in women with risk of venous thromboembolism? Blood Rev. 2017;31:151-157.
30. Rovinski D, Ramos RB, Fighera TM, et al. Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: a systematic review and meta-analysis. Thromb Res. 2018;168:83-95.
31. Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med. 2012;9:e1001275.
32. Kamphuisen PW, Beyer-Westendorf J. Bleeding complications during anticoagulant treatment in patients with cancer. Thromb Res. 2014;133(suppl 2):S49-S55.
33. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149:315-352.
34. Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol. 2013;31:2189-2204.
35. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902-4907.
36. Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood. 2010;116:5377-5382.
37. Carrier M, Abou-Nassar K, Mallick R, et al; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019;380:711-719.
38. Cobben MRR, Nemeth B, Lijfering WM, et al. Validation of risk assessment models for venous thrombosis in hospitalized medical patients. Res Pract Thromb Haemost. 2019;3:217-225.
39. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51:70-78.
40. Spyropoulos AC, Anderson FA Jr, FitzGerald G, et al; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140:706-714.
41. Kanaan AO, Silva MA, Donovan JL, et al. Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients. Clin Ther. 2007;29:2395-2405.
42. HJ, Cushman M, Burnett AE, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv. 2018;2:3198-3225.
43. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e278S-e325S.
44. Pannucci CJ, Swistun L, MacDonald JK, et al. Individualized venous thromboembolism risk stratification using the 2005 Caprini Score to identify the benefits and harms of chemoprophylaxis in surgical patients: a meta-analysis. Ann Surg. 2017;265:1094-1103.
45. Matharu GS, Kunutsor SK, Judge A, et al. Clinical effectiveness and safety of aspirin for venous thromboembolism prophylaxis after total hip and knee replacement: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2020;180:376-384.
46. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e227S-e277S.
47. Hull RD, Schellong SM, Tapson VF, et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recent reduced mobility: a randomized trial. Ann Intern Med. 2010;153:8-18.
48. Cohen AT, Harrington RA, Goldhaber SZ, et al. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016;375:534-544.
49. Rattan R, Parreco J, Eidelson SA, et al. Hidden burden of venous thromboembolism after trauma: a national analysis. J Trauma Acute Care Surg. 2018;85:899-906.
50. Yumoto T, Naito H, Yamakawa Y, et al. Venous thromboembolism in major trauma patients: a single-center retrospective cohort study of the epidemiology and utility of D-dimer for screening. Acute Med Surg. 2017;4:394-400.
51. Barrera LM, Perel P, Ker K, et al. Thromboprophylaxis for trauma patients. Cochrane Database Syst Rev. 2013(3):CD008303.
Venous thromboembolism (VTE) is a common and dangerous disease, affecting 0.1%-0.2% of the population annually—a rate that might be underreported.1 VTE is a collective term for venous blood clots, including (1) deep vein thrombosis (DVT) of peripheral veins and (2) pulmonary embolism, which occurs after a clot travels through the heart and becomes lodged in the pulmonary vasculature. Two-thirds of VTE cases present clinically as DVT2; most mortality from VTE disease is caused by the 20% of cases of pulmonary embolism that present as sudden death.1
VTE is comparable to myocardial infarction (MI) in incidence and severity. In 2008, 208 of every 100,000 people had an MI, with a 30-day mortality of 16/100,0003; VTE disease has an annual incidence of 161 of every 100,000 people and a 28-day mortality of 18/100,000.4 Although the incidence and severity of MI are steadily decreasing, the rate of VTE appears constant.3,5 The high mortality of VTE suggests that primary prevention, which we discuss in this article, is valuable (see “Key points: Primary prevention of venous thromboembolism”).
SIDEBAR
Key points: Primary prevention of venous thromboembolism
- Primary prevention of venous thromboembolism (VTE), a disease with mortality similar to myocardial infarction, should be an important consideration in at-risk patients.
- Although statins reduce the risk of VTE, their use is justified only if they are also required for prevention of cardiovascular disease.
- The risk of travel-related VTE can be reduced by wearing compression stockings.
- The choice of particular methods of contraception and of hormone replacement therapy can reduce VTE risk.
- Because of the risk of bleeding, using anticoagulants for primary prevention of VTE is justified only in certain circumstances.
- Pregnancy is the only condition in which there is a guideline indication for thrombophilia testing, because test results in this setting can change recommendations for preventing VTE.
- Using a risk-stratification model is key to determining risk in both medically and surgically hospitalized patients. Trauma and major orthopedic surgery always place the patient at high risk of VTE.
Risk factors
Virchow’s triad of venous stasis, vascular injury, and hypercoagulability describes predisposing factors for VTE.6 Although venous valves promote blood flow, they produce isolated low-flow areas adjacent to valves that become concentrated and locally hypoxic, increasing the risk of clotting.7 The great majority of DVTs (≥ 96%) occur in the lower extremity,8 starting in the calf; there, 75% of cases resolve spontaneously before they extend into the deep veins of the proximal leg.7 One-half of DVTs that do move into the proximal leg eventually embolize.7
Major risk factors for VTE comprise inherited conditions, medical history, medical therapeutics, and behaviors (TABLE 1).9-11 Unlike the preventive management of coronary artery disease (CAD), there is no simple, generalized prevention algorithm to address VTE risk factors.
Risk factors for VTE and CAD overlap. Risk factors for atherosclerosis—obesity, diabetes, smoking, hypertension, hyperlipidemia—also increase the risk of VTE (TABLE 1).9-11 The association between risk factors for VTE and atherosclerosis is demonstrated by a doubling of the risk of MI and stroke in the year following VTE.11 Lifestyle changes are expected to reduce the risk of VTE, as they do for acute CAD, but studies are lacking to confirm this connection. There is no prospective evidence showing that weight loss or control of diabetes or hypertension reduces the risk of VTE.12 Smoking cessation does appear to reduce risk: Former smokers have the same VTE risk as never-smokers.13
Thrombophilia testing: Not generally useful
Inherited and acquired thrombophilic conditions define a group of disorders in which the risk of VTE is increased. Although thrombophilia testing was once considered for primary and secondary prevention of VTE, such testing is rarely used now because proof of benefit is lacking: A large case–control study showed that thrombophilia testing did not predict recurrence after a first VTE.14 Guidelines of the American College of Chest Physicians (ACCP) do not address thrombophilia, and the American Society of Hematology recommends against thrombophilia testing after a provoked VTE.15,16
Primary prophylaxis of patients with a family history of VTE and inherited thrombophilia is controversial. Patients with both a family history of VTE and demonstrated thrombophilia do have double the average incidence of VTE, but this increased risk does not offset the significant bleeding risk associated with anticoagulation.17 Recommendations for thrombophilia testing are limited to certain situations in pregnancy, discussed in a bit.16,18,19
Continue to: Primary prevention of VTE in the clinic
Primary prevention of VTE in the clinic
There is no single, overarching preventive strategy for VTE in an ambulatory patient (although statins, discussed in a moment, offer some benefit, broadly). There are, however, distinct behavioral characteristics and medical circumstances for which opportunities exist to reduce VTE risk—for example, when a person engages in long-distance travel, receives hormonal therapy, is pregnant, or has cancer. In each scenario, recognizing and mitigating risk are important.
Statins offer a (slight) benefit
There is evidence that statins reduce the risk of VTE—slightly20-23:
- A large randomized, controlled trial showed that rosuvastatin, 20 mg/d, reduced the rate of VTE, compared to placebo; however, the 2-year number needed to treat (NNT) was 349.20 The VTE benefit is minimal, however, compared to primary prevention of cardiovascular disease with statins (5-year NNT = 56).21 The sole significant adverse event associated with statins was new-onset type 2 diabetes (5-year number needed to harm = 235).21
- A subsequent meta-analysis confirmed a small reduction in VTE risk with statins.22 In its 2012 guidelines, ACCP declined to issue a recommendation on the use of statins for VTE prevention.23 When considering statins for primary cardiovascular disease prevention, take the additional VTE prevention into account.
Simple strategies can help prevent travel-related VTE
Travel is a common inciting factor for VTE. A systematic review showed that VTE risk triples after travel of ≥ 4 hours, increasing by 20% with each additional 2 hours.24 Most VTE occurs in travelers who have other VTE risk factors.25 Based on case–control studies,23 guidelines recommend these preventive measures:
- frequent calf exercises
- sitting in an aisle seat during air travel
- keeping hydrated.
A Cochrane review showed that graded compression stockings reduce asymptomatic DVT in travelers by a factor of 10, in high- and low-risk patients.26
VTE risk varies with type of hormonal contraception
Most contraceptives increase VTE risk (TABLE 227,28). Risk with combined oral contraceptives varies with the amount of estrogen and progesterone. To reduce VTE risk with oral contraceptives, patients can use an agent that contains a lower dose of estrogen or one in which levonorgestrel replaces other progesterones.27
Continue to: Studies suggest that the levonorgestrel-releasing...
Studies suggest that the levonorgestrel-releasing intrauterine device and progestin-only pills are not associated with an increase in VTE risk.27 Although the quality of evidence varies, most nonoral hormonal contraceptives have been determined to carry a risk of VTE that is similar to that of combined oral contraceptives.28
In hormone replacement, avoid pills to lower risk
Hormone replacement therapy (HRT) for postmenopausal women increases VTE risk when administered in oral form, with combined estrogen and progestin HRT doubling the risk and estrogen-only formulations having a lower risk.29 VTE risk is highest in the first 6 months of HRT, declining to that of a non-HRT user within 5 years.29 Neither transdermal HRT nor estrogen creams increase the risk of VTE, according to a systematic review.30 The estradiol-containing vaginal ring also does not confer increased risk.29
Pregnancy, thrombophilia, and VTE prevention
VTE affects as many as 0.2% of pregnancies but causes 9% of pregnancy-related deaths.18 The severity of VTE in pregnancy led the American College of Obstetricians and Gynecologists (ACOG) to recommend primary VTE prophylaxis in patients with certain thrombophilias.18 Thrombophilia testing is recommended in patients with proven high-risk thrombophilia in a first-degree relative.18 ACOG recognizes 5 thrombophilias considered to carry a high risk of VTE in pregnancy18:
- homozygous Factor V Leiden
- homozygous prothrombin G20210A mutation
- antithrombin deficiency
- heterozygous Factor V Leiden and prothrombin G20210A mutation
- antiphospholipid antibody syndrome.
ACOG recommends limiting thrombophilia testing to (1) any specific thrombophilia carried by a relative and (2) possibly, the antiphospholipid antibodies anticardiolipin and lupus anticoagulant.18,19 Antiphospholipid testing is recommended when there is a history of stillbirth, 3 early pregnancy losses, or delivery earlier than 34 weeks secondary to preeclampsia.19
Primary VTE prophylaxis is recommended for pregnant patients with a high-risk thrombophilia; low-molecular-weight heparin (LMWH) is safe and its effects are predictable.18 Because postpartum risk of VTE is higher than antepartum risk, postpartum prophylaxis is also recommended with lower-risk thrombophilias18; a vitamin K antagonist or LMWH can be used.18 ACCP and ACOG recommendations for VTE prophylaxis in pregnancy differ slightly (TABLE 316,18,19).
Continue to: Cancer increases risks of VTE and bleeding
Cancer increases risks of VTE and bleeding
Cancer increases VTE risk > 6-fold31; metastases, chemotherapy, and radiotherapy further increase risk. Cancer also greatly increases the risk of bleeding: Cancer patients with VTE have an annual major bleeding rate ≥ 20%.32 Guidelines do not recommend primary VTE prophylaxis for cancer, although American Society of Clinical Oncology guidelines discuss consideration of prophylaxis for select, high-risk patients,33,34 including those with multiple myeloma, metastatic gastrointestinal cancer, or metastatic brain cancer.31,34 Recent evidence (discussed in a moment) supports the use of apixaban for primary VTE prevention during chemotherapy for high-risk cancer.
The Khorana Risk Score (TABLE 435,36) for VTE was developed and validated for use in patients with solid cancer35: A score of 2 conveys nearly a 10% risk of VTE over 6 months.36 A recent study of 550 cancer patients with a Khorana score of ≥ 2—the first evidence of risk-guided primary VTE prevention in cancer—showed that primary prophylaxis with 2.5 mg of apixaban, bid, reduced the risk of VTE (NNT = 17); however, the number needed to harm (for major bleeding) was 59.37 Mortality was not changed with apixaban treatment
Primary VTE prevention in med-surg hospitalizations
The risk of VTE increases significantly during hospitalization, although not enough to justify universal prophylaxis. Recommended prevention strategies for different classes of hospitalized patients are summarized below.
In medically hospitalized patients, risk is stratified with a risk-assessment model. Medically hospitalized patients have, on average, a VTE risk of 1.2%23; 12 risk-assessment models designed to stratify risk were recently compared.38 Two models, the Caprini Score (TABLE 5)39 and the IMPROVE VTE Risk Calculator,40 were best able to identify low-risk patients (negative predictive value, > 99%).38 American Society of Hematology guidelines recommend IMPROVE VTE or the Padua Prediction Score for risk stratification.41 While the Caprini score only designates 11% of eventual VTE cases as low risk, both the IMPROVE VTE and Padua scores miss more than 35% of eventual VTE.38
Because LMWH prophylaxis has been shown to reduce VTE by 40% without increasing the risk of major bleeding, using Caprini should prevent 2 VTEs for every 1000 patients, without an increase in major bleeding and with 13 additional minor bleeding events.42
Continue to: Critically ill patients
Critically ill patients are assumed to be at high risk of VTE and do not require stratification.23 For high-risk patients, prophylaxis with LMWH, low-dose unfractionated heparin (LDUH), or fondaparinux is recommended for the duration of admission.23 For patients at high risk of both VTE and bleeding, mechanical prophylaxis with intermittent pneumatic compression (IPC) is recommended instead of LMWH, LDUH, or fondaparinux.23
Surgery, like trauma (see next page), increases the risk of VTE and has been well studied. Prophylaxis after orthopedic surgery differs from that of other types of surgery.
In orthopedic surgery, risk depends on the procedure. For major orthopedic surgery, including total hip or knee arthroplasty and hip fracture surgery, VTE prophylaxis is recommended for 35 days postsurgically.43 LMWH is the preferred agent, although many other means have been shown to be beneficial.44 A recent systematic review demonstrated that aspirin is not inferior to other medications after hip or knee arthroplasty.45 No mechanical or pharmacotherapeutic prophylaxis is generally recommended after nonmajor orthopedic surgery.43
Nonorthopedic surgery is stratified by risk factors, using Caprini44 (TABLE 539). For medium-risk patients (Caprini score, 3-4) LDUH, LMWH, or IPC is recommended; for high-risk patients (Caprini score, ≥ 5) preventive treatment should combine pharmacotherapeutic and mechanical prophylaxis.46 A recent meta-analysis, comprising 14,776 patients, showed that surgical patients with a Caprini score ≥ 7 had a reduced incidence of VTE when given chemoprophylaxis, whereas patients whose score is < 7 do not benefit from chemoprophylaxis.43 When bleeding risk is high, IPC is recommended as sole therapy.43 Prophylaxis is not recommended when risk (determined by the Caprini score) is low.46
Post-hospitalization. Risk of VTE can persist for as long as 90 days after hospitalization; this finding has led to evaluation of the benefit of prolonged chemoprophylaxis.23 Extended-duration LMWH prophylaxis decreases the incidence of VTE, but at the cost of increased risk of major bleeding.47 Based on this evidence, guidelines recommend against prolonged-duration anticoagulation.23 A 2016 trial showed that 35 days of the direct-acting anticoagulant betrixaban reduced the risk of symptomatic VTE events, compared to 10 days of LMWH (NNT = 167), without increased risk of bleeding.48 This is a limited benefit, however, that is unlikely to change guideline recommendations.
Continue to: Trauma
Trauma: VTE risk increases with severity
Trauma increases the risk of VTE considerably. A national study showed that 1.5% of admitted trauma patients experienced VTE during hospitalization and that 1.2% were readmitted for VTE within 1 year.49 As many as 32% of trauma patients admitted to the intensive care unit experience VTE despite appropriate prophylaxis.50 A Cochrane Review51 found that:
- prophylaxis significantly reduces DVT risk
- pharmacotherapeutic prophylaxis is more effective than mechanical prophylaxis
- LMWH is more effective than LDUH.
Guidelines recommend that major trauma patients receive prophylaxis with LMWH, LDUH, or IPC.46
CORRESPONDENCE
Michael J. Arnold, MD, CDR, MC, USN; Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Jacksonville, FL 32214; [email protected].
Venous thromboembolism (VTE) is a common and dangerous disease, affecting 0.1%-0.2% of the population annually—a rate that might be underreported.1 VTE is a collective term for venous blood clots, including (1) deep vein thrombosis (DVT) of peripheral veins and (2) pulmonary embolism, which occurs after a clot travels through the heart and becomes lodged in the pulmonary vasculature. Two-thirds of VTE cases present clinically as DVT2; most mortality from VTE disease is caused by the 20% of cases of pulmonary embolism that present as sudden death.1
VTE is comparable to myocardial infarction (MI) in incidence and severity. In 2008, 208 of every 100,000 people had an MI, with a 30-day mortality of 16/100,0003; VTE disease has an annual incidence of 161 of every 100,000 people and a 28-day mortality of 18/100,000.4 Although the incidence and severity of MI are steadily decreasing, the rate of VTE appears constant.3,5 The high mortality of VTE suggests that primary prevention, which we discuss in this article, is valuable (see “Key points: Primary prevention of venous thromboembolism”).
SIDEBAR
Key points: Primary prevention of venous thromboembolism
- Primary prevention of venous thromboembolism (VTE), a disease with mortality similar to myocardial infarction, should be an important consideration in at-risk patients.
- Although statins reduce the risk of VTE, their use is justified only if they are also required for prevention of cardiovascular disease.
- The risk of travel-related VTE can be reduced by wearing compression stockings.
- The choice of particular methods of contraception and of hormone replacement therapy can reduce VTE risk.
- Because of the risk of bleeding, using anticoagulants for primary prevention of VTE is justified only in certain circumstances.
- Pregnancy is the only condition in which there is a guideline indication for thrombophilia testing, because test results in this setting can change recommendations for preventing VTE.
- Using a risk-stratification model is key to determining risk in both medically and surgically hospitalized patients. Trauma and major orthopedic surgery always place the patient at high risk of VTE.
Risk factors
Virchow’s triad of venous stasis, vascular injury, and hypercoagulability describes predisposing factors for VTE.6 Although venous valves promote blood flow, they produce isolated low-flow areas adjacent to valves that become concentrated and locally hypoxic, increasing the risk of clotting.7 The great majority of DVTs (≥ 96%) occur in the lower extremity,8 starting in the calf; there, 75% of cases resolve spontaneously before they extend into the deep veins of the proximal leg.7 One-half of DVTs that do move into the proximal leg eventually embolize.7
Major risk factors for VTE comprise inherited conditions, medical history, medical therapeutics, and behaviors (TABLE 1).9-11 Unlike the preventive management of coronary artery disease (CAD), there is no simple, generalized prevention algorithm to address VTE risk factors.
Risk factors for VTE and CAD overlap. Risk factors for atherosclerosis—obesity, diabetes, smoking, hypertension, hyperlipidemia—also increase the risk of VTE (TABLE 1).9-11 The association between risk factors for VTE and atherosclerosis is demonstrated by a doubling of the risk of MI and stroke in the year following VTE.11 Lifestyle changes are expected to reduce the risk of VTE, as they do for acute CAD, but studies are lacking to confirm this connection. There is no prospective evidence showing that weight loss or control of diabetes or hypertension reduces the risk of VTE.12 Smoking cessation does appear to reduce risk: Former smokers have the same VTE risk as never-smokers.13
Thrombophilia testing: Not generally useful
Inherited and acquired thrombophilic conditions define a group of disorders in which the risk of VTE is increased. Although thrombophilia testing was once considered for primary and secondary prevention of VTE, such testing is rarely used now because proof of benefit is lacking: A large case–control study showed that thrombophilia testing did not predict recurrence after a first VTE.14 Guidelines of the American College of Chest Physicians (ACCP) do not address thrombophilia, and the American Society of Hematology recommends against thrombophilia testing after a provoked VTE.15,16
Primary prophylaxis of patients with a family history of VTE and inherited thrombophilia is controversial. Patients with both a family history of VTE and demonstrated thrombophilia do have double the average incidence of VTE, but this increased risk does not offset the significant bleeding risk associated with anticoagulation.17 Recommendations for thrombophilia testing are limited to certain situations in pregnancy, discussed in a bit.16,18,19
Continue to: Primary prevention of VTE in the clinic
Primary prevention of VTE in the clinic
There is no single, overarching preventive strategy for VTE in an ambulatory patient (although statins, discussed in a moment, offer some benefit, broadly). There are, however, distinct behavioral characteristics and medical circumstances for which opportunities exist to reduce VTE risk—for example, when a person engages in long-distance travel, receives hormonal therapy, is pregnant, or has cancer. In each scenario, recognizing and mitigating risk are important.
Statins offer a (slight) benefit
There is evidence that statins reduce the risk of VTE—slightly20-23:
- A large randomized, controlled trial showed that rosuvastatin, 20 mg/d, reduced the rate of VTE, compared to placebo; however, the 2-year number needed to treat (NNT) was 349.20 The VTE benefit is minimal, however, compared to primary prevention of cardiovascular disease with statins (5-year NNT = 56).21 The sole significant adverse event associated with statins was new-onset type 2 diabetes (5-year number needed to harm = 235).21
- A subsequent meta-analysis confirmed a small reduction in VTE risk with statins.22 In its 2012 guidelines, ACCP declined to issue a recommendation on the use of statins for VTE prevention.23 When considering statins for primary cardiovascular disease prevention, take the additional VTE prevention into account.
Simple strategies can help prevent travel-related VTE
Travel is a common inciting factor for VTE. A systematic review showed that VTE risk triples after travel of ≥ 4 hours, increasing by 20% with each additional 2 hours.24 Most VTE occurs in travelers who have other VTE risk factors.25 Based on case–control studies,23 guidelines recommend these preventive measures:
- frequent calf exercises
- sitting in an aisle seat during air travel
- keeping hydrated.
A Cochrane review showed that graded compression stockings reduce asymptomatic DVT in travelers by a factor of 10, in high- and low-risk patients.26
VTE risk varies with type of hormonal contraception
Most contraceptives increase VTE risk (TABLE 227,28). Risk with combined oral contraceptives varies with the amount of estrogen and progesterone. To reduce VTE risk with oral contraceptives, patients can use an agent that contains a lower dose of estrogen or one in which levonorgestrel replaces other progesterones.27
Continue to: Studies suggest that the levonorgestrel-releasing...
Studies suggest that the levonorgestrel-releasing intrauterine device and progestin-only pills are not associated with an increase in VTE risk.27 Although the quality of evidence varies, most nonoral hormonal contraceptives have been determined to carry a risk of VTE that is similar to that of combined oral contraceptives.28
In hormone replacement, avoid pills to lower risk
Hormone replacement therapy (HRT) for postmenopausal women increases VTE risk when administered in oral form, with combined estrogen and progestin HRT doubling the risk and estrogen-only formulations having a lower risk.29 VTE risk is highest in the first 6 months of HRT, declining to that of a non-HRT user within 5 years.29 Neither transdermal HRT nor estrogen creams increase the risk of VTE, according to a systematic review.30 The estradiol-containing vaginal ring also does not confer increased risk.29
Pregnancy, thrombophilia, and VTE prevention
VTE affects as many as 0.2% of pregnancies but causes 9% of pregnancy-related deaths.18 The severity of VTE in pregnancy led the American College of Obstetricians and Gynecologists (ACOG) to recommend primary VTE prophylaxis in patients with certain thrombophilias.18 Thrombophilia testing is recommended in patients with proven high-risk thrombophilia in a first-degree relative.18 ACOG recognizes 5 thrombophilias considered to carry a high risk of VTE in pregnancy18:
- homozygous Factor V Leiden
- homozygous prothrombin G20210A mutation
- antithrombin deficiency
- heterozygous Factor V Leiden and prothrombin G20210A mutation
- antiphospholipid antibody syndrome.
ACOG recommends limiting thrombophilia testing to (1) any specific thrombophilia carried by a relative and (2) possibly, the antiphospholipid antibodies anticardiolipin and lupus anticoagulant.18,19 Antiphospholipid testing is recommended when there is a history of stillbirth, 3 early pregnancy losses, or delivery earlier than 34 weeks secondary to preeclampsia.19
Primary VTE prophylaxis is recommended for pregnant patients with a high-risk thrombophilia; low-molecular-weight heparin (LMWH) is safe and its effects are predictable.18 Because postpartum risk of VTE is higher than antepartum risk, postpartum prophylaxis is also recommended with lower-risk thrombophilias18; a vitamin K antagonist or LMWH can be used.18 ACCP and ACOG recommendations for VTE prophylaxis in pregnancy differ slightly (TABLE 316,18,19).
Continue to: Cancer increases risks of VTE and bleeding
Cancer increases risks of VTE and bleeding
Cancer increases VTE risk > 6-fold31; metastases, chemotherapy, and radiotherapy further increase risk. Cancer also greatly increases the risk of bleeding: Cancer patients with VTE have an annual major bleeding rate ≥ 20%.32 Guidelines do not recommend primary VTE prophylaxis for cancer, although American Society of Clinical Oncology guidelines discuss consideration of prophylaxis for select, high-risk patients,33,34 including those with multiple myeloma, metastatic gastrointestinal cancer, or metastatic brain cancer.31,34 Recent evidence (discussed in a moment) supports the use of apixaban for primary VTE prevention during chemotherapy for high-risk cancer.
The Khorana Risk Score (TABLE 435,36) for VTE was developed and validated for use in patients with solid cancer35: A score of 2 conveys nearly a 10% risk of VTE over 6 months.36 A recent study of 550 cancer patients with a Khorana score of ≥ 2—the first evidence of risk-guided primary VTE prevention in cancer—showed that primary prophylaxis with 2.5 mg of apixaban, bid, reduced the risk of VTE (NNT = 17); however, the number needed to harm (for major bleeding) was 59.37 Mortality was not changed with apixaban treatment
Primary VTE prevention in med-surg hospitalizations
The risk of VTE increases significantly during hospitalization, although not enough to justify universal prophylaxis. Recommended prevention strategies for different classes of hospitalized patients are summarized below.
In medically hospitalized patients, risk is stratified with a risk-assessment model. Medically hospitalized patients have, on average, a VTE risk of 1.2%23; 12 risk-assessment models designed to stratify risk were recently compared.38 Two models, the Caprini Score (TABLE 5)39 and the IMPROVE VTE Risk Calculator,40 were best able to identify low-risk patients (negative predictive value, > 99%).38 American Society of Hematology guidelines recommend IMPROVE VTE or the Padua Prediction Score for risk stratification.41 While the Caprini score only designates 11% of eventual VTE cases as low risk, both the IMPROVE VTE and Padua scores miss more than 35% of eventual VTE.38
Because LMWH prophylaxis has been shown to reduce VTE by 40% without increasing the risk of major bleeding, using Caprini should prevent 2 VTEs for every 1000 patients, without an increase in major bleeding and with 13 additional minor bleeding events.42
Continue to: Critically ill patients
Critically ill patients are assumed to be at high risk of VTE and do not require stratification.23 For high-risk patients, prophylaxis with LMWH, low-dose unfractionated heparin (LDUH), or fondaparinux is recommended for the duration of admission.23 For patients at high risk of both VTE and bleeding, mechanical prophylaxis with intermittent pneumatic compression (IPC) is recommended instead of LMWH, LDUH, or fondaparinux.23
Surgery, like trauma (see next page), increases the risk of VTE and has been well studied. Prophylaxis after orthopedic surgery differs from that of other types of surgery.
In orthopedic surgery, risk depends on the procedure. For major orthopedic surgery, including total hip or knee arthroplasty and hip fracture surgery, VTE prophylaxis is recommended for 35 days postsurgically.43 LMWH is the preferred agent, although many other means have been shown to be beneficial.44 A recent systematic review demonstrated that aspirin is not inferior to other medications after hip or knee arthroplasty.45 No mechanical or pharmacotherapeutic prophylaxis is generally recommended after nonmajor orthopedic surgery.43
Nonorthopedic surgery is stratified by risk factors, using Caprini44 (TABLE 539). For medium-risk patients (Caprini score, 3-4) LDUH, LMWH, or IPC is recommended; for high-risk patients (Caprini score, ≥ 5) preventive treatment should combine pharmacotherapeutic and mechanical prophylaxis.46 A recent meta-analysis, comprising 14,776 patients, showed that surgical patients with a Caprini score ≥ 7 had a reduced incidence of VTE when given chemoprophylaxis, whereas patients whose score is < 7 do not benefit from chemoprophylaxis.43 When bleeding risk is high, IPC is recommended as sole therapy.43 Prophylaxis is not recommended when risk (determined by the Caprini score) is low.46
Post-hospitalization. Risk of VTE can persist for as long as 90 days after hospitalization; this finding has led to evaluation of the benefit of prolonged chemoprophylaxis.23 Extended-duration LMWH prophylaxis decreases the incidence of VTE, but at the cost of increased risk of major bleeding.47 Based on this evidence, guidelines recommend against prolonged-duration anticoagulation.23 A 2016 trial showed that 35 days of the direct-acting anticoagulant betrixaban reduced the risk of symptomatic VTE events, compared to 10 days of LMWH (NNT = 167), without increased risk of bleeding.48 This is a limited benefit, however, that is unlikely to change guideline recommendations.
Continue to: Trauma
Trauma: VTE risk increases with severity
Trauma increases the risk of VTE considerably. A national study showed that 1.5% of admitted trauma patients experienced VTE during hospitalization and that 1.2% were readmitted for VTE within 1 year.49 As many as 32% of trauma patients admitted to the intensive care unit experience VTE despite appropriate prophylaxis.50 A Cochrane Review51 found that:
- prophylaxis significantly reduces DVT risk
- pharmacotherapeutic prophylaxis is more effective than mechanical prophylaxis
- LMWH is more effective than LDUH.
Guidelines recommend that major trauma patients receive prophylaxis with LMWH, LDUH, or IPC.46
CORRESPONDENCE
Michael J. Arnold, MD, CDR, MC, USN; Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Jacksonville, FL 32214; [email protected].
1. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010. 38(4 suppl):S495-S501.
2. Tagalakis V, Patenaude V, Kahn SR, et al. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE Study Cohort. Am J Med. 2013;126:832.e13-e21.
3. Yeh RW, Sidney S, Chandra M, et al. Population trends in the incidence and outcomes of acute myocardial infarction. N Engl J Med. 2010. 362:2155-2165.
4. Cushman M, Tsai AW, White RH, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med. 2004;117:19-25.
5. Goldhaber SZ. Venous thromboembolism: epidemiology and magnitude of the problem. Best Pract Res Clin Haematol. 2012;25:235-242.
6. Stone J, Hangge P, Albadawi H, et al. Deep vein thrombosis: pathogenesis, diagnosis, and medical management. Cardiovasc Diagn Ther. 2017;7(suppl 3):S276-S284.
7. Olaf M, Cooney R. Deep venous thrombosis. Emerg Med Clin North Am. 2017;35:743-770.
8. Sajid MS, Ahmed N, Desai M, et al. Upper limb deep vein thrombosis: a literature review to streamline the protocol for management. Acta Haematol. 2007;118:10-18.
9. Bates SM, Ginsberg JS. Clinical practice. Treatment of deep-vein thrombosis. N Engl J Med. 2004;351:268-277.
10. Chandra D, Parisini E, Mozaffarian D. Meta-analysis: travel and risk for venous thromboembolism. Ann Intern Med. 2009;151:180-190.
11. Goldhaber SZ. Risk factors for venous thromboembolism. J Am Col Cardiol. 2010;56:1-7.
12. Yang G, De Staercke C, Hooper WC. The effects of obesity on venous thromboembolism: a review. Open J Prev Med. 2012;2:499-509.
13. Severinsen MT, Kristensen SR, Johnsen SP, et al. Smoking and venous thromboembolism: a Danish follow-up study. J Thromb Haemost. 2009;7:1297-1303.
14. Coppens M, Reijnders JH, Middeldorp S, et al. Testing for inherited thrombophilia does not reduce the recurrence of venous thrombosis. J Thromb Haemost. 2008;6:1474-1477.
15. Choosing Wisely. American Society of Hematology. Ten things physicians and patients should question. www.choosingwisely.org/societies/american-society-of-hematology/. Accessed September 28, 2020.
16. Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e691S-e736S.
17. Vossen CY, Conard J, Fontcuberta J, et al. Risk of a first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prospective Cohort on Thrombophilia (EPCOT). J Thromb Haemost. 2005;3:459-464.
18. Practice Bulletin No. 197: Inherited thrombophilias in pregnancy. Obstet Gynecol. 2018;132:e18-e34.
19. Committee on Practice Bulletins—Obstetrics, American College of Obstetricians and Gynecologists. Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol. 2012;120:1514-1521.
20. Glynn RJ, Danielson E, Fonseca FAH, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med. 2009;360:1851-1861.
21. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013(1):CD004816.
22. Squizzato A, Galli M, Romualdi E, et al. Statins, fibrates, and venous thromboembolism: a meta-analysis. Eur Heart J. 2010;31:1248-1256.
23. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e195S-e226S.
24. Kelman CW, Kortt MA, Becker NG, et al. Deep vein thrombosis and air travel: record linkage study. BMJ. 2003;327:1072.
25. Johnston RV, Hudson MF; . Travelers’ thrombosis. Aviat Space Environ Med. 2014;85:191-194.
26. Clarke MJ, Broderick C, Hopewell S, et al. Compression stockings for preventing deep vein thrombosis in airline passengers. Cochrane Database Syst Rev. 2016;9:CD004002.
27. van Hylckama Vlieg A, Middledorp S. Hormone therapies and venous thromboembolism: where are we now? J Thromb Haemost. 2011;9:257-266.
28. Tepper NK, Dragoman MV, Gaffield ME, et al. Nonoral combined hormonal contraceptives and thromboembolism: a systematic review. Contraception. 2017;95:130-139.
29. Lekovic D, Miljic P, Dmitrovic A, et al. How do you decide on hormone replacement therapy in women with risk of venous thromboembolism? Blood Rev. 2017;31:151-157.
30. Rovinski D, Ramos RB, Fighera TM, et al. Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: a systematic review and meta-analysis. Thromb Res. 2018;168:83-95.
31. Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med. 2012;9:e1001275.
32. Kamphuisen PW, Beyer-Westendorf J. Bleeding complications during anticoagulant treatment in patients with cancer. Thromb Res. 2014;133(suppl 2):S49-S55.
33. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149:315-352.
34. Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol. 2013;31:2189-2204.
35. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902-4907.
36. Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood. 2010;116:5377-5382.
37. Carrier M, Abou-Nassar K, Mallick R, et al; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019;380:711-719.
38. Cobben MRR, Nemeth B, Lijfering WM, et al. Validation of risk assessment models for venous thrombosis in hospitalized medical patients. Res Pract Thromb Haemost. 2019;3:217-225.
39. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51:70-78.
40. Spyropoulos AC, Anderson FA Jr, FitzGerald G, et al; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140:706-714.
41. Kanaan AO, Silva MA, Donovan JL, et al. Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients. Clin Ther. 2007;29:2395-2405.
42. HJ, Cushman M, Burnett AE, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv. 2018;2:3198-3225.
43. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e278S-e325S.
44. Pannucci CJ, Swistun L, MacDonald JK, et al. Individualized venous thromboembolism risk stratification using the 2005 Caprini Score to identify the benefits and harms of chemoprophylaxis in surgical patients: a meta-analysis. Ann Surg. 2017;265:1094-1103.
45. Matharu GS, Kunutsor SK, Judge A, et al. Clinical effectiveness and safety of aspirin for venous thromboembolism prophylaxis after total hip and knee replacement: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2020;180:376-384.
46. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e227S-e277S.
47. Hull RD, Schellong SM, Tapson VF, et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recent reduced mobility: a randomized trial. Ann Intern Med. 2010;153:8-18.
48. Cohen AT, Harrington RA, Goldhaber SZ, et al. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016;375:534-544.
49. Rattan R, Parreco J, Eidelson SA, et al. Hidden burden of venous thromboembolism after trauma: a national analysis. J Trauma Acute Care Surg. 2018;85:899-906.
50. Yumoto T, Naito H, Yamakawa Y, et al. Venous thromboembolism in major trauma patients: a single-center retrospective cohort study of the epidemiology and utility of D-dimer for screening. Acute Med Surg. 2017;4:394-400.
51. Barrera LM, Perel P, Ker K, et al. Thromboprophylaxis for trauma patients. Cochrane Database Syst Rev. 2013(3):CD008303.
1. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010. 38(4 suppl):S495-S501.
2. Tagalakis V, Patenaude V, Kahn SR, et al. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE Study Cohort. Am J Med. 2013;126:832.e13-e21.
3. Yeh RW, Sidney S, Chandra M, et al. Population trends in the incidence and outcomes of acute myocardial infarction. N Engl J Med. 2010. 362:2155-2165.
4. Cushman M, Tsai AW, White RH, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med. 2004;117:19-25.
5. Goldhaber SZ. Venous thromboembolism: epidemiology and magnitude of the problem. Best Pract Res Clin Haematol. 2012;25:235-242.
6. Stone J, Hangge P, Albadawi H, et al. Deep vein thrombosis: pathogenesis, diagnosis, and medical management. Cardiovasc Diagn Ther. 2017;7(suppl 3):S276-S284.
7. Olaf M, Cooney R. Deep venous thrombosis. Emerg Med Clin North Am. 2017;35:743-770.
8. Sajid MS, Ahmed N, Desai M, et al. Upper limb deep vein thrombosis: a literature review to streamline the protocol for management. Acta Haematol. 2007;118:10-18.
9. Bates SM, Ginsberg JS. Clinical practice. Treatment of deep-vein thrombosis. N Engl J Med. 2004;351:268-277.
10. Chandra D, Parisini E, Mozaffarian D. Meta-analysis: travel and risk for venous thromboembolism. Ann Intern Med. 2009;151:180-190.
11. Goldhaber SZ. Risk factors for venous thromboembolism. J Am Col Cardiol. 2010;56:1-7.
12. Yang G, De Staercke C, Hooper WC. The effects of obesity on venous thromboembolism: a review. Open J Prev Med. 2012;2:499-509.
13. Severinsen MT, Kristensen SR, Johnsen SP, et al. Smoking and venous thromboembolism: a Danish follow-up study. J Thromb Haemost. 2009;7:1297-1303.
14. Coppens M, Reijnders JH, Middeldorp S, et al. Testing for inherited thrombophilia does not reduce the recurrence of venous thrombosis. J Thromb Haemost. 2008;6:1474-1477.
15. Choosing Wisely. American Society of Hematology. Ten things physicians and patients should question. www.choosingwisely.org/societies/american-society-of-hematology/. Accessed September 28, 2020.
16. Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e691S-e736S.
17. Vossen CY, Conard J, Fontcuberta J, et al. Risk of a first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prospective Cohort on Thrombophilia (EPCOT). J Thromb Haemost. 2005;3:459-464.
18. Practice Bulletin No. 197: Inherited thrombophilias in pregnancy. Obstet Gynecol. 2018;132:e18-e34.
19. Committee on Practice Bulletins—Obstetrics, American College of Obstetricians and Gynecologists. Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol. 2012;120:1514-1521.
20. Glynn RJ, Danielson E, Fonseca FAH, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med. 2009;360:1851-1861.
21. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013(1):CD004816.
22. Squizzato A, Galli M, Romualdi E, et al. Statins, fibrates, and venous thromboembolism: a meta-analysis. Eur Heart J. 2010;31:1248-1256.
23. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e195S-e226S.
24. Kelman CW, Kortt MA, Becker NG, et al. Deep vein thrombosis and air travel: record linkage study. BMJ. 2003;327:1072.
25. Johnston RV, Hudson MF; . Travelers’ thrombosis. Aviat Space Environ Med. 2014;85:191-194.
26. Clarke MJ, Broderick C, Hopewell S, et al. Compression stockings for preventing deep vein thrombosis in airline passengers. Cochrane Database Syst Rev. 2016;9:CD004002.
27. van Hylckama Vlieg A, Middledorp S. Hormone therapies and venous thromboembolism: where are we now? J Thromb Haemost. 2011;9:257-266.
28. Tepper NK, Dragoman MV, Gaffield ME, et al. Nonoral combined hormonal contraceptives and thromboembolism: a systematic review. Contraception. 2017;95:130-139.
29. Lekovic D, Miljic P, Dmitrovic A, et al. How do you decide on hormone replacement therapy in women with risk of venous thromboembolism? Blood Rev. 2017;31:151-157.
30. Rovinski D, Ramos RB, Fighera TM, et al. Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: a systematic review and meta-analysis. Thromb Res. 2018;168:83-95.
31. Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med. 2012;9:e1001275.
32. Kamphuisen PW, Beyer-Westendorf J. Bleeding complications during anticoagulant treatment in patients with cancer. Thromb Res. 2014;133(suppl 2):S49-S55.
33. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149:315-352.
34. Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol. 2013;31:2189-2204.
35. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902-4907.
36. Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood. 2010;116:5377-5382.
37. Carrier M, Abou-Nassar K, Mallick R, et al; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019;380:711-719.
38. Cobben MRR, Nemeth B, Lijfering WM, et al. Validation of risk assessment models for venous thrombosis in hospitalized medical patients. Res Pract Thromb Haemost. 2019;3:217-225.
39. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51:70-78.
40. Spyropoulos AC, Anderson FA Jr, FitzGerald G, et al; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140:706-714.
41. Kanaan AO, Silva MA, Donovan JL, et al. Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients. Clin Ther. 2007;29:2395-2405.
42. HJ, Cushman M, Burnett AE, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv. 2018;2:3198-3225.
43. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e278S-e325S.
44. Pannucci CJ, Swistun L, MacDonald JK, et al. Individualized venous thromboembolism risk stratification using the 2005 Caprini Score to identify the benefits and harms of chemoprophylaxis in surgical patients: a meta-analysis. Ann Surg. 2017;265:1094-1103.
45. Matharu GS, Kunutsor SK, Judge A, et al. Clinical effectiveness and safety of aspirin for venous thromboembolism prophylaxis after total hip and knee replacement: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2020;180:376-384.
46. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e227S-e277S.
47. Hull RD, Schellong SM, Tapson VF, et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recent reduced mobility: a randomized trial. Ann Intern Med. 2010;153:8-18.
48. Cohen AT, Harrington RA, Goldhaber SZ, et al. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016;375:534-544.
49. Rattan R, Parreco J, Eidelson SA, et al. Hidden burden of venous thromboembolism after trauma: a national analysis. J Trauma Acute Care Surg. 2018;85:899-906.
50. Yumoto T, Naito H, Yamakawa Y, et al. Venous thromboembolism in major trauma patients: a single-center retrospective cohort study of the epidemiology and utility of D-dimer for screening. Acute Med Surg. 2017;4:394-400.
51. Barrera LM, Perel P, Ker K, et al. Thromboprophylaxis for trauma patients. Cochrane Database Syst Rev. 2013(3):CD008303.
PRACTICE RECOMMENDATIONS
› Consider the mild reduction in the risk of venous thromboembolism (VTE) provided by statins when contemplating their use for cardiovascular disease prevention. B
› Avoid testing for thrombophilia to determine the risk of VTE, except in pregnant patients who meet criteria for antiphospholipid syndrome or have a family history of VTE. B
› Recommend an intrauterine device or progestin-only pill for contraception if the patient’s risk of VTE is high. B
› Stratify hospitalized medical and nonorthopedic surgical patients by risk score to determine the need for VTE prophylaxis. B
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
Adrenal vein sampling looms as choke point for aldosteronism assessment of hypertensives
At a time when new evidence strongly suggests that roughly a fifth of patents with hypertension have primary aldosteronism as the cause, other recent findings suggest that many of these possibly tens of millions of patients with aldosterone-driven high blood pressure may as a consequence need an expensive and not-widely-available diagnostic test – adrenal vein sampling – to determine whether they are candidates for a definitive surgical cure to their aldosteronism.
Some endocrinologists worry the worldwide infrastructure for running adrenal vein sampling (AVS) isn’t close to being in place to deliver on this looming need for patients with primary aldosteronism (PA), especially given the burgeoning numbers now being cited for PA prevalence.
“The system could be overwhelmed,” warned Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville. “Right now, adrenal vein sampling [AVS] is the gold standard,” for distinguishing unilateral and bilateral excess aldosterone secretion, “but not every radiologist can do AVS. Until we find a surrogate biomarker that can distinguish unilateral and bilateral PA” many patients will need AVS, Dr. Carey said in an interview.
“AVS is important for accurate lateralization of aldosterone excess in patients, but it may not be feasible for all patients with PA to undergo AVS. If the prevalence of PA truly is on the order of 15% [of all patients with hypertension] then health systems would be stretched to offer all of them AVS, which is technically challenging and requires dedicated training and is therefore limited to expert centers,” commented Jun Yang, MBBS, a cardiovascular endocrinologist at the Hudson Institute of Medical Research and a hypertension researcher at Monash University, both in Melbourne. “At Monash, our interventional radiologists have increased their [AVS] success rate from 40% to more than 90% during the past 10 years, and our waiting list for patients scheduled for AVS is now 3-4 months long,” Dr. Yang said in an interview.
Finding a unilateral adrenal nodule as the cause of PA means that surgical removal is an option, a step that often fully resolves the PA and normalizes blood pressure. Patients with a bilateral source of the aldosterone are not candidates for surgical cure and must be managed with medical treatment, usually a mineralocorticoid receptor antagonist such as spironolactone that can neutralize or at least reduce the impact of hyperaldosteronism.
AVS finds unilateral adenomas when imaging can’t
The evidence that raised concerns about the reliability of imaging as an easier and noninvasive means to identify hypertensive patients with PA and a unilateral adrenal nodule that makes them candidates for surgical removal to resolve their PA and hypertension came out in May 2020 in a review of 174 PA patients who underwent AVS at a single center in Calgary, Alta., during 2006-2018.
The review included 366 patients with PA referred to the University of Calgary for assessment, of whom 179 had no adrenal nodule visible with either CT or MRI imaging, with 174 of these patients also undergoing successful AVS. The procedure revealed 70 patients (40%) had unilateral aldosterone secretion (Can J Cardiol. 2020 May 16. doi: 10.1016/j.cjca.2020.05.013).
In an editorial about this report that appeared a few weeks later, Ross D. Feldman, MD, a hypertension-management researcher and professor of medicine at the University of Manitoba in Winnipeg, Man., said the finding was “amazing,” and “confirms that lateralization of aldosterone secretion in a patient with PA but without an identifiable mass on that side is not a zebra,” but instead a presentation that “occurs in almost half of patients with PA and no discernible adenoma on the side that lateralizes.” (Can J. Cardiol. 2020 Jul 3. doi: 10.1016/j.cjca.2020.06.022).
Although this was just one center’s experience, the authors are not alone in making this finding, although prior reports seem to have been largely forgotten or ignored until now.
“The discordance between AVS and adrenal imaging has been documented by numerous groups, and in our own experience [in Melbourne] around 40% of patients with unilateral aldosterone excess do not have a distinct unilateral adenoma on CT,” said Dr. Yang.
“Here’s the problem,” summed up Dr. Feldman in an interview. “Nearly half of patients with hyperaldosteronism don’t localize based on a CT or MRI, so you have to do AVS, but AVS is not generally available; it’s only at tertiary centers; and you have to do a lot of them,” to do them well. “It’s a half-day procedure, and you have to hit the correct adrenal vein.”
AVS for millions?
Compounding the challenge is the other bit of bombshell news recently dropped on the endocrinology and hypertension communities: PA may be much more prevalent that previously suspected, occurring in roughly 20% of patients with hypertension, according to study results that also came out in 2020 (Ann Int Med. 2020 Jul 7;173[1]:10-20).
The upshot, according to Dr. Feldman and others, is that researchers will need to find reliable criteria besides imaging for identifying PA patients with an increased likelihood of having a lateralized source for their excess aldosterone production. That’s “the only hope,” said Dr. Feldman, “so we won’t have to do AVS on 20 million Americans.”
Unfortunately, the path toward a successful screen to winnow down candidates for AVS has been long and not especially fruitful, with efforts dating back at least 50 years, and with one of the most recent efforts at stratifying PA patients by certain laboratory measures getting dismissed as producing a benefit that “might not be substantial,” wrote Michael Stowasser, MBBS, in a published commentary (J Hypertension. 2020 Jul;38[7]:1259-61).
In contrast to Dr. Feldman, Dr. Stowasser was more optimistic about the prospects for avoiding an immediate crisis in AVS assessment of PA patients, mostly because so few patients with PA are now identified by clinicians. Given the poor record clinicians have historically rung up diagnosing PA, “it would seem unlikely that we are going to be flooded with AVS requests any time soon,” he wrote. There is also reason to hope that increased demand for AVS will help broaden availability, and innovative testing methods promise to speed up the procedure, said Dr. Stowasser, a professor of medicine at the University of Queensland in Brisbane, Australia and director of the Endocrine Hypertension Research Centre at Greenslopes and Princess Alexandra Hospitals in Brisbane, in an interview.
But regardless of whether AVS testing becomes more available or streamlined, recent events suggest there will be little way to avoid eventually having to run millions of these diagnostic procedures.
Patients with PA “who decide they will not want surgery do not need AVS. For all other patients with PA, you need AVS. The medical system will just have to respond,” Dr. Carey concluded.
Dr. Carey, Dr. Yang, Dr. Feldman, and Dr. Stowasser had no relevant disclosures.
At a time when new evidence strongly suggests that roughly a fifth of patents with hypertension have primary aldosteronism as the cause, other recent findings suggest that many of these possibly tens of millions of patients with aldosterone-driven high blood pressure may as a consequence need an expensive and not-widely-available diagnostic test – adrenal vein sampling – to determine whether they are candidates for a definitive surgical cure to their aldosteronism.
Some endocrinologists worry the worldwide infrastructure for running adrenal vein sampling (AVS) isn’t close to being in place to deliver on this looming need for patients with primary aldosteronism (PA), especially given the burgeoning numbers now being cited for PA prevalence.
“The system could be overwhelmed,” warned Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville. “Right now, adrenal vein sampling [AVS] is the gold standard,” for distinguishing unilateral and bilateral excess aldosterone secretion, “but not every radiologist can do AVS. Until we find a surrogate biomarker that can distinguish unilateral and bilateral PA” many patients will need AVS, Dr. Carey said in an interview.
“AVS is important for accurate lateralization of aldosterone excess in patients, but it may not be feasible for all patients with PA to undergo AVS. If the prevalence of PA truly is on the order of 15% [of all patients with hypertension] then health systems would be stretched to offer all of them AVS, which is technically challenging and requires dedicated training and is therefore limited to expert centers,” commented Jun Yang, MBBS, a cardiovascular endocrinologist at the Hudson Institute of Medical Research and a hypertension researcher at Monash University, both in Melbourne. “At Monash, our interventional radiologists have increased their [AVS] success rate from 40% to more than 90% during the past 10 years, and our waiting list for patients scheduled for AVS is now 3-4 months long,” Dr. Yang said in an interview.
Finding a unilateral adrenal nodule as the cause of PA means that surgical removal is an option, a step that often fully resolves the PA and normalizes blood pressure. Patients with a bilateral source of the aldosterone are not candidates for surgical cure and must be managed with medical treatment, usually a mineralocorticoid receptor antagonist such as spironolactone that can neutralize or at least reduce the impact of hyperaldosteronism.
AVS finds unilateral adenomas when imaging can’t
The evidence that raised concerns about the reliability of imaging as an easier and noninvasive means to identify hypertensive patients with PA and a unilateral adrenal nodule that makes them candidates for surgical removal to resolve their PA and hypertension came out in May 2020 in a review of 174 PA patients who underwent AVS at a single center in Calgary, Alta., during 2006-2018.
The review included 366 patients with PA referred to the University of Calgary for assessment, of whom 179 had no adrenal nodule visible with either CT or MRI imaging, with 174 of these patients also undergoing successful AVS. The procedure revealed 70 patients (40%) had unilateral aldosterone secretion (Can J Cardiol. 2020 May 16. doi: 10.1016/j.cjca.2020.05.013).
In an editorial about this report that appeared a few weeks later, Ross D. Feldman, MD, a hypertension-management researcher and professor of medicine at the University of Manitoba in Winnipeg, Man., said the finding was “amazing,” and “confirms that lateralization of aldosterone secretion in a patient with PA but without an identifiable mass on that side is not a zebra,” but instead a presentation that “occurs in almost half of patients with PA and no discernible adenoma on the side that lateralizes.” (Can J. Cardiol. 2020 Jul 3. doi: 10.1016/j.cjca.2020.06.022).
Although this was just one center’s experience, the authors are not alone in making this finding, although prior reports seem to have been largely forgotten or ignored until now.
“The discordance between AVS and adrenal imaging has been documented by numerous groups, and in our own experience [in Melbourne] around 40% of patients with unilateral aldosterone excess do not have a distinct unilateral adenoma on CT,” said Dr. Yang.
“Here’s the problem,” summed up Dr. Feldman in an interview. “Nearly half of patients with hyperaldosteronism don’t localize based on a CT or MRI, so you have to do AVS, but AVS is not generally available; it’s only at tertiary centers; and you have to do a lot of them,” to do them well. “It’s a half-day procedure, and you have to hit the correct adrenal vein.”
AVS for millions?
Compounding the challenge is the other bit of bombshell news recently dropped on the endocrinology and hypertension communities: PA may be much more prevalent that previously suspected, occurring in roughly 20% of patients with hypertension, according to study results that also came out in 2020 (Ann Int Med. 2020 Jul 7;173[1]:10-20).
The upshot, according to Dr. Feldman and others, is that researchers will need to find reliable criteria besides imaging for identifying PA patients with an increased likelihood of having a lateralized source for their excess aldosterone production. That’s “the only hope,” said Dr. Feldman, “so we won’t have to do AVS on 20 million Americans.”
Unfortunately, the path toward a successful screen to winnow down candidates for AVS has been long and not especially fruitful, with efforts dating back at least 50 years, and with one of the most recent efforts at stratifying PA patients by certain laboratory measures getting dismissed as producing a benefit that “might not be substantial,” wrote Michael Stowasser, MBBS, in a published commentary (J Hypertension. 2020 Jul;38[7]:1259-61).
In contrast to Dr. Feldman, Dr. Stowasser was more optimistic about the prospects for avoiding an immediate crisis in AVS assessment of PA patients, mostly because so few patients with PA are now identified by clinicians. Given the poor record clinicians have historically rung up diagnosing PA, “it would seem unlikely that we are going to be flooded with AVS requests any time soon,” he wrote. There is also reason to hope that increased demand for AVS will help broaden availability, and innovative testing methods promise to speed up the procedure, said Dr. Stowasser, a professor of medicine at the University of Queensland in Brisbane, Australia and director of the Endocrine Hypertension Research Centre at Greenslopes and Princess Alexandra Hospitals in Brisbane, in an interview.
But regardless of whether AVS testing becomes more available or streamlined, recent events suggest there will be little way to avoid eventually having to run millions of these diagnostic procedures.
Patients with PA “who decide they will not want surgery do not need AVS. For all other patients with PA, you need AVS. The medical system will just have to respond,” Dr. Carey concluded.
Dr. Carey, Dr. Yang, Dr. Feldman, and Dr. Stowasser had no relevant disclosures.
At a time when new evidence strongly suggests that roughly a fifth of patents with hypertension have primary aldosteronism as the cause, other recent findings suggest that many of these possibly tens of millions of patients with aldosterone-driven high blood pressure may as a consequence need an expensive and not-widely-available diagnostic test – adrenal vein sampling – to determine whether they are candidates for a definitive surgical cure to their aldosteronism.
Some endocrinologists worry the worldwide infrastructure for running adrenal vein sampling (AVS) isn’t close to being in place to deliver on this looming need for patients with primary aldosteronism (PA), especially given the burgeoning numbers now being cited for PA prevalence.
“The system could be overwhelmed,” warned Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville. “Right now, adrenal vein sampling [AVS] is the gold standard,” for distinguishing unilateral and bilateral excess aldosterone secretion, “but not every radiologist can do AVS. Until we find a surrogate biomarker that can distinguish unilateral and bilateral PA” many patients will need AVS, Dr. Carey said in an interview.
“AVS is important for accurate lateralization of aldosterone excess in patients, but it may not be feasible for all patients with PA to undergo AVS. If the prevalence of PA truly is on the order of 15% [of all patients with hypertension] then health systems would be stretched to offer all of them AVS, which is technically challenging and requires dedicated training and is therefore limited to expert centers,” commented Jun Yang, MBBS, a cardiovascular endocrinologist at the Hudson Institute of Medical Research and a hypertension researcher at Monash University, both in Melbourne. “At Monash, our interventional radiologists have increased their [AVS] success rate from 40% to more than 90% during the past 10 years, and our waiting list for patients scheduled for AVS is now 3-4 months long,” Dr. Yang said in an interview.
Finding a unilateral adrenal nodule as the cause of PA means that surgical removal is an option, a step that often fully resolves the PA and normalizes blood pressure. Patients with a bilateral source of the aldosterone are not candidates for surgical cure and must be managed with medical treatment, usually a mineralocorticoid receptor antagonist such as spironolactone that can neutralize or at least reduce the impact of hyperaldosteronism.
AVS finds unilateral adenomas when imaging can’t
The evidence that raised concerns about the reliability of imaging as an easier and noninvasive means to identify hypertensive patients with PA and a unilateral adrenal nodule that makes them candidates for surgical removal to resolve their PA and hypertension came out in May 2020 in a review of 174 PA patients who underwent AVS at a single center in Calgary, Alta., during 2006-2018.
The review included 366 patients with PA referred to the University of Calgary for assessment, of whom 179 had no adrenal nodule visible with either CT or MRI imaging, with 174 of these patients also undergoing successful AVS. The procedure revealed 70 patients (40%) had unilateral aldosterone secretion (Can J Cardiol. 2020 May 16. doi: 10.1016/j.cjca.2020.05.013).
In an editorial about this report that appeared a few weeks later, Ross D. Feldman, MD, a hypertension-management researcher and professor of medicine at the University of Manitoba in Winnipeg, Man., said the finding was “amazing,” and “confirms that lateralization of aldosterone secretion in a patient with PA but without an identifiable mass on that side is not a zebra,” but instead a presentation that “occurs in almost half of patients with PA and no discernible adenoma on the side that lateralizes.” (Can J. Cardiol. 2020 Jul 3. doi: 10.1016/j.cjca.2020.06.022).
Although this was just one center’s experience, the authors are not alone in making this finding, although prior reports seem to have been largely forgotten or ignored until now.
“The discordance between AVS and adrenal imaging has been documented by numerous groups, and in our own experience [in Melbourne] around 40% of patients with unilateral aldosterone excess do not have a distinct unilateral adenoma on CT,” said Dr. Yang.
“Here’s the problem,” summed up Dr. Feldman in an interview. “Nearly half of patients with hyperaldosteronism don’t localize based on a CT or MRI, so you have to do AVS, but AVS is not generally available; it’s only at tertiary centers; and you have to do a lot of them,” to do them well. “It’s a half-day procedure, and you have to hit the correct adrenal vein.”
AVS for millions?
Compounding the challenge is the other bit of bombshell news recently dropped on the endocrinology and hypertension communities: PA may be much more prevalent that previously suspected, occurring in roughly 20% of patients with hypertension, according to study results that also came out in 2020 (Ann Int Med. 2020 Jul 7;173[1]:10-20).
The upshot, according to Dr. Feldman and others, is that researchers will need to find reliable criteria besides imaging for identifying PA patients with an increased likelihood of having a lateralized source for their excess aldosterone production. That’s “the only hope,” said Dr. Feldman, “so we won’t have to do AVS on 20 million Americans.”
Unfortunately, the path toward a successful screen to winnow down candidates for AVS has been long and not especially fruitful, with efforts dating back at least 50 years, and with one of the most recent efforts at stratifying PA patients by certain laboratory measures getting dismissed as producing a benefit that “might not be substantial,” wrote Michael Stowasser, MBBS, in a published commentary (J Hypertension. 2020 Jul;38[7]:1259-61).
In contrast to Dr. Feldman, Dr. Stowasser was more optimistic about the prospects for avoiding an immediate crisis in AVS assessment of PA patients, mostly because so few patients with PA are now identified by clinicians. Given the poor record clinicians have historically rung up diagnosing PA, “it would seem unlikely that we are going to be flooded with AVS requests any time soon,” he wrote. There is also reason to hope that increased demand for AVS will help broaden availability, and innovative testing methods promise to speed up the procedure, said Dr. Stowasser, a professor of medicine at the University of Queensland in Brisbane, Australia and director of the Endocrine Hypertension Research Centre at Greenslopes and Princess Alexandra Hospitals in Brisbane, in an interview.
But regardless of whether AVS testing becomes more available or streamlined, recent events suggest there will be little way to avoid eventually having to run millions of these diagnostic procedures.
Patients with PA “who decide they will not want surgery do not need AVS. For all other patients with PA, you need AVS. The medical system will just have to respond,” Dr. Carey concluded.
Dr. Carey, Dr. Yang, Dr. Feldman, and Dr. Stowasser had no relevant disclosures.
AHA issues new scientific statement on heart health for LGBTQ adults
Cardiovascular health should be routinely assessed and addressed in LGBTQ adults, the American Heart Association concluded in a new scientific statement.
“Among the most important takeaways from this scientific statement is the need for health care providers in clinical settings to routinely assess sexual orientation and gender identity,” Billy A. Caceres, PhD, RN, chair of the statement writing group, said in an interview.
“This will help health care providers engage LGBTQ patients in discussions about their heart health that account for the unique experiences of this population,” said Dr. Caceres, assistant professor at Columbia University, New York.
The statement was published online Oct. 8 in Circulation.
‘Invisible’ population
There are roughly 11 million LGBTQ adults in the United States, yet they are often “invisible in health care settings and cardiovascular research,” Dr. Caceres noted. The AHA scientific statement is the first from a national organization in the United States to comprehensively summarize the evidence on cardiovascular (CV) research in LGBTQ adults.
There is mounting evidence that LGBTQ adults experience worse CV health relative to their cisgender heterosexual peers. Disparities in CV health may be driven by unique psychosocial stressors in the LGBTQ individuals such as family rejection and anxiety of concealment of their sexual orientation or gender identity.
While there is limited information on the CV health of LGBTQ people, the writing group said providers should be aware of the following:
- LGBTQ adults are more likely to use tobacco than their cisgender heterosexual peers.
- Transgender adults may be less physically active than their cisgender counterparts. Gender-affirming care might play a role in promoting physical activity among transgender people.
- Transgender women may be at increased risk for heart disease because of behavioral and clinical factors (such as the use of gender-affirming hormones like estrogen).
- Transgender women and nonbinary persons are more likely to binge drink.
- Lesbian and bisexual women have a higher prevalence of obesity than heterosexual women do.
“We need to better understand how to support LGBTQ adults in optimizing their CV health. To do this, we will need rigorous research that examines potential explanations for the CV health disparities that have been observed in LGBTQ adults,” Dr. Caceres said.
He noted that research is also needed within the LGBTQ population among groups that might be at greater risk for heart disease, including racial- and ethnic-minority and low-income LGBTQ adults.
“Researchers should also design and test evidence-based interventions to promote the heart health of LGBTQ adults. This is an area that is greatly lacking within CV health research,” said Dr. Caceres.
Discrimination in health care
Discrimination against LGBTQ adults in health care settings also remains a problem, the authors noted.
The writing group cites data showing that nearly 56% of sexual-minority and 70% of gender-minority adults report having experienced some form of discrimination from clinicians, including the use of harsh/abusive language.
“Perhaps most alarming,” roughly 8% of sexual-minority and 25% of transgender individuals have been denied health care by clinicians, they noted.
“LGBTQ individuals are delaying primary care and preventative visits because there is a great fear of being treated differently. Being treated differently often means receiving inadequate or inferior care because of sexual orientation or gender identity,” Dr. Caceres said in a news release.
The writing group calls for greater emphasis on LGBTQ health issues in the education of all health care providers. Dr. Caceres said it’s “paramount to include content about LGBTQ health in clinical training and licensure requirements in order to address these cardiovascular health disparities.”
Traditionally, there has been very little LGBTQ-related content in health care professional education training. A 2018 online survey of students at 10 medical schools found that approximately 80% of students did not feel competent to provide care for transgender patients.
But that may soon change. In September 2020, the Accreditation Review Commission on Education for the Physician Assistant began requiring LGBTQ curricular content, the writing group notes.
The AHA scientific statement on LGBTQ was developed by the writing group on behalf of the AHA Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, the Council on Lifestyle and Cardiometabolic Health, the Council on Peripheral Vascular Disease, and the Stroke Council.
A version of this article originally appeared on Medscape.com.
Cardiovascular health should be routinely assessed and addressed in LGBTQ adults, the American Heart Association concluded in a new scientific statement.
“Among the most important takeaways from this scientific statement is the need for health care providers in clinical settings to routinely assess sexual orientation and gender identity,” Billy A. Caceres, PhD, RN, chair of the statement writing group, said in an interview.
“This will help health care providers engage LGBTQ patients in discussions about their heart health that account for the unique experiences of this population,” said Dr. Caceres, assistant professor at Columbia University, New York.
The statement was published online Oct. 8 in Circulation.
‘Invisible’ population
There are roughly 11 million LGBTQ adults in the United States, yet they are often “invisible in health care settings and cardiovascular research,” Dr. Caceres noted. The AHA scientific statement is the first from a national organization in the United States to comprehensively summarize the evidence on cardiovascular (CV) research in LGBTQ adults.
There is mounting evidence that LGBTQ adults experience worse CV health relative to their cisgender heterosexual peers. Disparities in CV health may be driven by unique psychosocial stressors in the LGBTQ individuals such as family rejection and anxiety of concealment of their sexual orientation or gender identity.
While there is limited information on the CV health of LGBTQ people, the writing group said providers should be aware of the following:
- LGBTQ adults are more likely to use tobacco than their cisgender heterosexual peers.
- Transgender adults may be less physically active than their cisgender counterparts. Gender-affirming care might play a role in promoting physical activity among transgender people.
- Transgender women may be at increased risk for heart disease because of behavioral and clinical factors (such as the use of gender-affirming hormones like estrogen).
- Transgender women and nonbinary persons are more likely to binge drink.
- Lesbian and bisexual women have a higher prevalence of obesity than heterosexual women do.
“We need to better understand how to support LGBTQ adults in optimizing their CV health. To do this, we will need rigorous research that examines potential explanations for the CV health disparities that have been observed in LGBTQ adults,” Dr. Caceres said.
He noted that research is also needed within the LGBTQ population among groups that might be at greater risk for heart disease, including racial- and ethnic-minority and low-income LGBTQ adults.
“Researchers should also design and test evidence-based interventions to promote the heart health of LGBTQ adults. This is an area that is greatly lacking within CV health research,” said Dr. Caceres.
Discrimination in health care
Discrimination against LGBTQ adults in health care settings also remains a problem, the authors noted.
The writing group cites data showing that nearly 56% of sexual-minority and 70% of gender-minority adults report having experienced some form of discrimination from clinicians, including the use of harsh/abusive language.
“Perhaps most alarming,” roughly 8% of sexual-minority and 25% of transgender individuals have been denied health care by clinicians, they noted.
“LGBTQ individuals are delaying primary care and preventative visits because there is a great fear of being treated differently. Being treated differently often means receiving inadequate or inferior care because of sexual orientation or gender identity,” Dr. Caceres said in a news release.
The writing group calls for greater emphasis on LGBTQ health issues in the education of all health care providers. Dr. Caceres said it’s “paramount to include content about LGBTQ health in clinical training and licensure requirements in order to address these cardiovascular health disparities.”
Traditionally, there has been very little LGBTQ-related content in health care professional education training. A 2018 online survey of students at 10 medical schools found that approximately 80% of students did not feel competent to provide care for transgender patients.
But that may soon change. In September 2020, the Accreditation Review Commission on Education for the Physician Assistant began requiring LGBTQ curricular content, the writing group notes.
The AHA scientific statement on LGBTQ was developed by the writing group on behalf of the AHA Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, the Council on Lifestyle and Cardiometabolic Health, the Council on Peripheral Vascular Disease, and the Stroke Council.
A version of this article originally appeared on Medscape.com.
Cardiovascular health should be routinely assessed and addressed in LGBTQ adults, the American Heart Association concluded in a new scientific statement.
“Among the most important takeaways from this scientific statement is the need for health care providers in clinical settings to routinely assess sexual orientation and gender identity,” Billy A. Caceres, PhD, RN, chair of the statement writing group, said in an interview.
“This will help health care providers engage LGBTQ patients in discussions about their heart health that account for the unique experiences of this population,” said Dr. Caceres, assistant professor at Columbia University, New York.
The statement was published online Oct. 8 in Circulation.
‘Invisible’ population
There are roughly 11 million LGBTQ adults in the United States, yet they are often “invisible in health care settings and cardiovascular research,” Dr. Caceres noted. The AHA scientific statement is the first from a national organization in the United States to comprehensively summarize the evidence on cardiovascular (CV) research in LGBTQ adults.
There is mounting evidence that LGBTQ adults experience worse CV health relative to their cisgender heterosexual peers. Disparities in CV health may be driven by unique psychosocial stressors in the LGBTQ individuals such as family rejection and anxiety of concealment of their sexual orientation or gender identity.
While there is limited information on the CV health of LGBTQ people, the writing group said providers should be aware of the following:
- LGBTQ adults are more likely to use tobacco than their cisgender heterosexual peers.
- Transgender adults may be less physically active than their cisgender counterparts. Gender-affirming care might play a role in promoting physical activity among transgender people.
- Transgender women may be at increased risk for heart disease because of behavioral and clinical factors (such as the use of gender-affirming hormones like estrogen).
- Transgender women and nonbinary persons are more likely to binge drink.
- Lesbian and bisexual women have a higher prevalence of obesity than heterosexual women do.
“We need to better understand how to support LGBTQ adults in optimizing their CV health. To do this, we will need rigorous research that examines potential explanations for the CV health disparities that have been observed in LGBTQ adults,” Dr. Caceres said.
He noted that research is also needed within the LGBTQ population among groups that might be at greater risk for heart disease, including racial- and ethnic-minority and low-income LGBTQ adults.
“Researchers should also design and test evidence-based interventions to promote the heart health of LGBTQ adults. This is an area that is greatly lacking within CV health research,” said Dr. Caceres.
Discrimination in health care
Discrimination against LGBTQ adults in health care settings also remains a problem, the authors noted.
The writing group cites data showing that nearly 56% of sexual-minority and 70% of gender-minority adults report having experienced some form of discrimination from clinicians, including the use of harsh/abusive language.
“Perhaps most alarming,” roughly 8% of sexual-minority and 25% of transgender individuals have been denied health care by clinicians, they noted.
“LGBTQ individuals are delaying primary care and preventative visits because there is a great fear of being treated differently. Being treated differently often means receiving inadequate or inferior care because of sexual orientation or gender identity,” Dr. Caceres said in a news release.
The writing group calls for greater emphasis on LGBTQ health issues in the education of all health care providers. Dr. Caceres said it’s “paramount to include content about LGBTQ health in clinical training and licensure requirements in order to address these cardiovascular health disparities.”
Traditionally, there has been very little LGBTQ-related content in health care professional education training. A 2018 online survey of students at 10 medical schools found that approximately 80% of students did not feel competent to provide care for transgender patients.
But that may soon change. In September 2020, the Accreditation Review Commission on Education for the Physician Assistant began requiring LGBTQ curricular content, the writing group notes.
The AHA scientific statement on LGBTQ was developed by the writing group on behalf of the AHA Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, the Council on Lifestyle and Cardiometabolic Health, the Council on Peripheral Vascular Disease, and the Stroke Council.
A version of this article originally appeared on Medscape.com.
Benefit of rivaroxaban after limb revascularization greatest in those with comorbid CAD
The absolute benefit of adding low-dose rivaroxaban to low-dose aspirin following revascularization for symptomatic lower-extremity peripheral artery disease (PAD) is significantly greater in patients with comorbid coronary artery disease (CAD), according to a new secondary analysis of the VOYAGER PAD trial.
“These findings suggest heterogeneity of prognostic risk for ischemic events in lower-extremity PAD patients, and may support shared decision-making with these patients,” William R. Hiatt, MD, observed in presenting the study results at the virtual annual congress of the European Society of Cardiology.
VOYAGER PAD was a 3-year, 34-country clinical trial in which 6,564 patients with symptomatic PAD who had recently undergone lower-limb revascularization were randomized in double-blind fashion to rivaroxaban (Xarelto) at 2.5 mg twice daily or placebo on top of background standard therapy with low-dose aspirin.
Among the 2,067 participants with baseline comorbid CAD, the primary outcome – a composite comprised of cardiovascular death, acute MI, ischemic stroke, acute limb ischemia, and major amputation – occurred in 18.9% of the rivaroxaban group at 3 years and 24.3% on placebo, for a highly significant 22% relative risk reduction.
In contrast, in the 4,497 patients with PAD only, the primary outcome occurred in 16.1% of those on rivaroxaban and 17.9% of controls, an 11% relative risk reduction which failed to reach statistical significance. The absolute risk reduction achieved with rivaroxaban was 5.4% in patients with PAD plus CAD versus 1.8% in those with PAD alone. Thus, the significant clinical benefit with rivaroxaban plus aspirin previously reported in the overall study population, with a number needed to treat for 3 years of 39 in order to prevent one primary outcome event, was largely driven by the superior outcomes in the dual-diagnosis subgroup, reported Dr. Hiatt, professor of medicine at the University of Colorado at Denver, Aurora.
“A strategy of rivaroxaban at 2.5 mg twice daily plus low-dose aspirin versus low-dose aspirin alone reduces ischemic events of the limb, brain, and heart, but also increases bleeding, with an overall net benefit,” the cardiologist said. “In particular, the benefits of this strategy for MI and ischemic stroke are robust, especially in patients with PAD and CAD.”
Indeed, the MI rate at 3 years in the dual diagnosis subgroup was 7.3% with rivaroxaban and 8.8% with placebo, for a 23% relative risk reduction, compared with rates of 3.3% and 3.7%, respectively, in patients with PAD only. Similarly, ischemic stroke occurred in 2.9% of patients with PAD and CAD in the rivaroxaban group, compared with 3.9% with placebo, whereas the rate in the PAD only group was identical at 2.6% regardless of whether patients were on rivaroxaban or placebo.
In patients without CAD, the clinical benefit of rivaroxaban was driven by reductions in severe limb events. Their rate of acute limb ischemia was 5.2% with rivaroxaban, compared with 8.3% with placebo, for a 37% relative risk reduction. In contrast, the reduction in acute limb ischemia with rivaroxaban in patients with PAD and CAD wasn’t significantly different from placebo.
Thrombolysis in Myocardial Infarction major bleeding occurred in 2.4% of patients with PAD and CAD on rivaroxaban, compared with 1.1% on placebo, and in 1.7% and 1.5% of patients with PAD alone. Of note, rates of ischemic stroke or fatal hemorrhage were low and similar at less than 1% in all four groups, Dr. Hiatt noted.
VOYAGER PAD was sponsored by Bayer and Janssen. Dr. Hiatt reported receiving research grant support from those two companies as well as Amgen.
The absolute benefit of adding low-dose rivaroxaban to low-dose aspirin following revascularization for symptomatic lower-extremity peripheral artery disease (PAD) is significantly greater in patients with comorbid coronary artery disease (CAD), according to a new secondary analysis of the VOYAGER PAD trial.
“These findings suggest heterogeneity of prognostic risk for ischemic events in lower-extremity PAD patients, and may support shared decision-making with these patients,” William R. Hiatt, MD, observed in presenting the study results at the virtual annual congress of the European Society of Cardiology.
VOYAGER PAD was a 3-year, 34-country clinical trial in which 6,564 patients with symptomatic PAD who had recently undergone lower-limb revascularization were randomized in double-blind fashion to rivaroxaban (Xarelto) at 2.5 mg twice daily or placebo on top of background standard therapy with low-dose aspirin.
Among the 2,067 participants with baseline comorbid CAD, the primary outcome – a composite comprised of cardiovascular death, acute MI, ischemic stroke, acute limb ischemia, and major amputation – occurred in 18.9% of the rivaroxaban group at 3 years and 24.3% on placebo, for a highly significant 22% relative risk reduction.
In contrast, in the 4,497 patients with PAD only, the primary outcome occurred in 16.1% of those on rivaroxaban and 17.9% of controls, an 11% relative risk reduction which failed to reach statistical significance. The absolute risk reduction achieved with rivaroxaban was 5.4% in patients with PAD plus CAD versus 1.8% in those with PAD alone. Thus, the significant clinical benefit with rivaroxaban plus aspirin previously reported in the overall study population, with a number needed to treat for 3 years of 39 in order to prevent one primary outcome event, was largely driven by the superior outcomes in the dual-diagnosis subgroup, reported Dr. Hiatt, professor of medicine at the University of Colorado at Denver, Aurora.
“A strategy of rivaroxaban at 2.5 mg twice daily plus low-dose aspirin versus low-dose aspirin alone reduces ischemic events of the limb, brain, and heart, but also increases bleeding, with an overall net benefit,” the cardiologist said. “In particular, the benefits of this strategy for MI and ischemic stroke are robust, especially in patients with PAD and CAD.”
Indeed, the MI rate at 3 years in the dual diagnosis subgroup was 7.3% with rivaroxaban and 8.8% with placebo, for a 23% relative risk reduction, compared with rates of 3.3% and 3.7%, respectively, in patients with PAD only. Similarly, ischemic stroke occurred in 2.9% of patients with PAD and CAD in the rivaroxaban group, compared with 3.9% with placebo, whereas the rate in the PAD only group was identical at 2.6% regardless of whether patients were on rivaroxaban or placebo.
In patients without CAD, the clinical benefit of rivaroxaban was driven by reductions in severe limb events. Their rate of acute limb ischemia was 5.2% with rivaroxaban, compared with 8.3% with placebo, for a 37% relative risk reduction. In contrast, the reduction in acute limb ischemia with rivaroxaban in patients with PAD and CAD wasn’t significantly different from placebo.
Thrombolysis in Myocardial Infarction major bleeding occurred in 2.4% of patients with PAD and CAD on rivaroxaban, compared with 1.1% on placebo, and in 1.7% and 1.5% of patients with PAD alone. Of note, rates of ischemic stroke or fatal hemorrhage were low and similar at less than 1% in all four groups, Dr. Hiatt noted.
VOYAGER PAD was sponsored by Bayer and Janssen. Dr. Hiatt reported receiving research grant support from those two companies as well as Amgen.
The absolute benefit of adding low-dose rivaroxaban to low-dose aspirin following revascularization for symptomatic lower-extremity peripheral artery disease (PAD) is significantly greater in patients with comorbid coronary artery disease (CAD), according to a new secondary analysis of the VOYAGER PAD trial.
“These findings suggest heterogeneity of prognostic risk for ischemic events in lower-extremity PAD patients, and may support shared decision-making with these patients,” William R. Hiatt, MD, observed in presenting the study results at the virtual annual congress of the European Society of Cardiology.
VOYAGER PAD was a 3-year, 34-country clinical trial in which 6,564 patients with symptomatic PAD who had recently undergone lower-limb revascularization were randomized in double-blind fashion to rivaroxaban (Xarelto) at 2.5 mg twice daily or placebo on top of background standard therapy with low-dose aspirin.
Among the 2,067 participants with baseline comorbid CAD, the primary outcome – a composite comprised of cardiovascular death, acute MI, ischemic stroke, acute limb ischemia, and major amputation – occurred in 18.9% of the rivaroxaban group at 3 years and 24.3% on placebo, for a highly significant 22% relative risk reduction.
In contrast, in the 4,497 patients with PAD only, the primary outcome occurred in 16.1% of those on rivaroxaban and 17.9% of controls, an 11% relative risk reduction which failed to reach statistical significance. The absolute risk reduction achieved with rivaroxaban was 5.4% in patients with PAD plus CAD versus 1.8% in those with PAD alone. Thus, the significant clinical benefit with rivaroxaban plus aspirin previously reported in the overall study population, with a number needed to treat for 3 years of 39 in order to prevent one primary outcome event, was largely driven by the superior outcomes in the dual-diagnosis subgroup, reported Dr. Hiatt, professor of medicine at the University of Colorado at Denver, Aurora.
“A strategy of rivaroxaban at 2.5 mg twice daily plus low-dose aspirin versus low-dose aspirin alone reduces ischemic events of the limb, brain, and heart, but also increases bleeding, with an overall net benefit,” the cardiologist said. “In particular, the benefits of this strategy for MI and ischemic stroke are robust, especially in patients with PAD and CAD.”
Indeed, the MI rate at 3 years in the dual diagnosis subgroup was 7.3% with rivaroxaban and 8.8% with placebo, for a 23% relative risk reduction, compared with rates of 3.3% and 3.7%, respectively, in patients with PAD only. Similarly, ischemic stroke occurred in 2.9% of patients with PAD and CAD in the rivaroxaban group, compared with 3.9% with placebo, whereas the rate in the PAD only group was identical at 2.6% regardless of whether patients were on rivaroxaban or placebo.
In patients without CAD, the clinical benefit of rivaroxaban was driven by reductions in severe limb events. Their rate of acute limb ischemia was 5.2% with rivaroxaban, compared with 8.3% with placebo, for a 37% relative risk reduction. In contrast, the reduction in acute limb ischemia with rivaroxaban in patients with PAD and CAD wasn’t significantly different from placebo.
Thrombolysis in Myocardial Infarction major bleeding occurred in 2.4% of patients with PAD and CAD on rivaroxaban, compared with 1.1% on placebo, and in 1.7% and 1.5% of patients with PAD alone. Of note, rates of ischemic stroke or fatal hemorrhage were low and similar at less than 1% in all four groups, Dr. Hiatt noted.
VOYAGER PAD was sponsored by Bayer and Janssen. Dr. Hiatt reported receiving research grant support from those two companies as well as Amgen.
FROM ESC CONGRESS 2020
Empagliflozin cut PA pressures in heart failure patients
Elevated pulmonary artery diastolic pressure is “perhaps the best predictor of bad outcomes in patients with heart failure, including hospitalization and death,” and new evidence clearly showed that the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin cuts this metric in patients by a clinically significant amount, Mikhail Kosiborod, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America.
The evidence he collected from a total of 65 heart failure patients with either reduced or preserved ejection fraction is the first documentation from a randomized, controlled study to show a direct effect by a SGLT2 inhibitor on pulmonary artery (PA) pressures.
Other key findings were that the drop in PA diastolic pressure with empagliflozin treatment compared with placebo became discernible early (within the first 4 weeks on treatment), that the pressure-lowering effect steadily grew over time, and that it showed no link to the intensity of loop diuretic treatment, which held steady during 12 weeks on treatment and 13 weeks of overall monitoring.
The study’s primary endpoint was the change from baseline in PA diastolic pressure after 12 weeks on treatment. The 31 patients who completed the full 12-week course had an average drop in their PA diastolic pressure of about 1.5 mm Hg, compared with 28 patients who completed 12 weeks on placebo. Average PA diastolic pressure at baseline was about 21 mm Hg in both treatment arms, and on treatment this fell by more than 0.5 mm Hg among those who received empagliflozin and rose by close to 1 mm Hg among control patients.
“There appears to be a direct effect of empagliflozin on pulmonary artery pressure that’s not been previously demonstrated” by an SGLT2 inhibitor, Dr. Kosiborod said. “I think this is one mechanism of action” for this drug class. “If you control pulmonary artery filling pressures you can prevent hospitalizations and deaths.”
Small reductions matter
“Small pressure differences are particularly important for pulmonary hypertension,” commented Lynne W. Stevenson, MD, professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn., and the report’s designated discussant.
“In the Vanderbilt heart failure database, patients with a pulmonary artery mean pressure of 20-24 mm Hg had 30% higher mortality than patients with lower pressures,” Dr. Stevenson noted. “This has led to a new definition of pulmonary hypertension, a mean pulmonary artery pressure above at or above 20 mm Hg.”
In Dr. Kosiborod’s study, patients began with an average PA mean pressure of about 30 mm Hg, and empagliflozin treatment led to a reduction in this metric with about the same magnitude as its effect on PA diastolic pressure. Empagliflozin also produced a similar reduction in average PA systolic pressure.
A study built on ambulatory PA monitoring
The results “also provide more proof for the concept of ambulatory hemodynamic monitoring” in patients with heart failure to monitor their status, she added. The study enrolled only patients who had already received a CardioMEMS implant as part of their routine care. This device allows for frequent, noninvasive monitoring of PA pressures. Researchers collected PA pressure data from patients twice daily for the entire 13-week study.
The EMBRACE HF (Empagliflozin Impact on Hemodynamics in Patients With Heart Failure) study enrolled patients with established heart failure, a CardioMEMS implant, and New York Heart Association class II-IV symptoms at any of eight U.S. centers. Patients averaged about 65 years old, and slightly more than half had class III disease, which denotes marked limitation of physical activity.
Despite the brief treatment period, patients who received empagliflozin showed other evidence of benefit including a trend toward improved quality of life scores, reduced levels of two different forms of brain natriuretic peptide, and significant weight loss, compared with controls, that averaged 2.4 kg.
The mechanism by which empagliflozin and other drugs in its class might lower PA filling pressures is unclear, but Dr. Kosiborod stressed that the consistent level of loop diuretic use during the study seems to rule out a diuretic effect from the SGLT2 inhibitor as having a role. A pulmonary vasculature effect is “much more likely,” perhaps mediated through modified endothelial function and vasodilation, he suggested.
EMBRACE HF was funded by Boehringer Ingelheim, the company that markets empagliflozin (Jardiance) along with Eli Lilly. Dr. Kosiborod has received research support and honoraria from Boehringer Ingelheim, and he has received honoraria from several other companies. Dr. Stevenson had no disclosures.
Elevated pulmonary artery diastolic pressure is “perhaps the best predictor of bad outcomes in patients with heart failure, including hospitalization and death,” and new evidence clearly showed that the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin cuts this metric in patients by a clinically significant amount, Mikhail Kosiborod, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America.
The evidence he collected from a total of 65 heart failure patients with either reduced or preserved ejection fraction is the first documentation from a randomized, controlled study to show a direct effect by a SGLT2 inhibitor on pulmonary artery (PA) pressures.
Other key findings were that the drop in PA diastolic pressure with empagliflozin treatment compared with placebo became discernible early (within the first 4 weeks on treatment), that the pressure-lowering effect steadily grew over time, and that it showed no link to the intensity of loop diuretic treatment, which held steady during 12 weeks on treatment and 13 weeks of overall monitoring.
The study’s primary endpoint was the change from baseline in PA diastolic pressure after 12 weeks on treatment. The 31 patients who completed the full 12-week course had an average drop in their PA diastolic pressure of about 1.5 mm Hg, compared with 28 patients who completed 12 weeks on placebo. Average PA diastolic pressure at baseline was about 21 mm Hg in both treatment arms, and on treatment this fell by more than 0.5 mm Hg among those who received empagliflozin and rose by close to 1 mm Hg among control patients.
“There appears to be a direct effect of empagliflozin on pulmonary artery pressure that’s not been previously demonstrated” by an SGLT2 inhibitor, Dr. Kosiborod said. “I think this is one mechanism of action” for this drug class. “If you control pulmonary artery filling pressures you can prevent hospitalizations and deaths.”
Small reductions matter
“Small pressure differences are particularly important for pulmonary hypertension,” commented Lynne W. Stevenson, MD, professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn., and the report’s designated discussant.
“In the Vanderbilt heart failure database, patients with a pulmonary artery mean pressure of 20-24 mm Hg had 30% higher mortality than patients with lower pressures,” Dr. Stevenson noted. “This has led to a new definition of pulmonary hypertension, a mean pulmonary artery pressure above at or above 20 mm Hg.”
In Dr. Kosiborod’s study, patients began with an average PA mean pressure of about 30 mm Hg, and empagliflozin treatment led to a reduction in this metric with about the same magnitude as its effect on PA diastolic pressure. Empagliflozin also produced a similar reduction in average PA systolic pressure.
A study built on ambulatory PA monitoring
The results “also provide more proof for the concept of ambulatory hemodynamic monitoring” in patients with heart failure to monitor their status, she added. The study enrolled only patients who had already received a CardioMEMS implant as part of their routine care. This device allows for frequent, noninvasive monitoring of PA pressures. Researchers collected PA pressure data from patients twice daily for the entire 13-week study.
The EMBRACE HF (Empagliflozin Impact on Hemodynamics in Patients With Heart Failure) study enrolled patients with established heart failure, a CardioMEMS implant, and New York Heart Association class II-IV symptoms at any of eight U.S. centers. Patients averaged about 65 years old, and slightly more than half had class III disease, which denotes marked limitation of physical activity.
Despite the brief treatment period, patients who received empagliflozin showed other evidence of benefit including a trend toward improved quality of life scores, reduced levels of two different forms of brain natriuretic peptide, and significant weight loss, compared with controls, that averaged 2.4 kg.
The mechanism by which empagliflozin and other drugs in its class might lower PA filling pressures is unclear, but Dr. Kosiborod stressed that the consistent level of loop diuretic use during the study seems to rule out a diuretic effect from the SGLT2 inhibitor as having a role. A pulmonary vasculature effect is “much more likely,” perhaps mediated through modified endothelial function and vasodilation, he suggested.
EMBRACE HF was funded by Boehringer Ingelheim, the company that markets empagliflozin (Jardiance) along with Eli Lilly. Dr. Kosiborod has received research support and honoraria from Boehringer Ingelheim, and he has received honoraria from several other companies. Dr. Stevenson had no disclosures.
Elevated pulmonary artery diastolic pressure is “perhaps the best predictor of bad outcomes in patients with heart failure, including hospitalization and death,” and new evidence clearly showed that the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin cuts this metric in patients by a clinically significant amount, Mikhail Kosiborod, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America.
The evidence he collected from a total of 65 heart failure patients with either reduced or preserved ejection fraction is the first documentation from a randomized, controlled study to show a direct effect by a SGLT2 inhibitor on pulmonary artery (PA) pressures.
Other key findings were that the drop in PA diastolic pressure with empagliflozin treatment compared with placebo became discernible early (within the first 4 weeks on treatment), that the pressure-lowering effect steadily grew over time, and that it showed no link to the intensity of loop diuretic treatment, which held steady during 12 weeks on treatment and 13 weeks of overall monitoring.
The study’s primary endpoint was the change from baseline in PA diastolic pressure after 12 weeks on treatment. The 31 patients who completed the full 12-week course had an average drop in their PA diastolic pressure of about 1.5 mm Hg, compared with 28 patients who completed 12 weeks on placebo. Average PA diastolic pressure at baseline was about 21 mm Hg in both treatment arms, and on treatment this fell by more than 0.5 mm Hg among those who received empagliflozin and rose by close to 1 mm Hg among control patients.
“There appears to be a direct effect of empagliflozin on pulmonary artery pressure that’s not been previously demonstrated” by an SGLT2 inhibitor, Dr. Kosiborod said. “I think this is one mechanism of action” for this drug class. “If you control pulmonary artery filling pressures you can prevent hospitalizations and deaths.”
Small reductions matter
“Small pressure differences are particularly important for pulmonary hypertension,” commented Lynne W. Stevenson, MD, professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn., and the report’s designated discussant.
“In the Vanderbilt heart failure database, patients with a pulmonary artery mean pressure of 20-24 mm Hg had 30% higher mortality than patients with lower pressures,” Dr. Stevenson noted. “This has led to a new definition of pulmonary hypertension, a mean pulmonary artery pressure above at or above 20 mm Hg.”
In Dr. Kosiborod’s study, patients began with an average PA mean pressure of about 30 mm Hg, and empagliflozin treatment led to a reduction in this metric with about the same magnitude as its effect on PA diastolic pressure. Empagliflozin also produced a similar reduction in average PA systolic pressure.
A study built on ambulatory PA monitoring
The results “also provide more proof for the concept of ambulatory hemodynamic monitoring” in patients with heart failure to monitor their status, she added. The study enrolled only patients who had already received a CardioMEMS implant as part of their routine care. This device allows for frequent, noninvasive monitoring of PA pressures. Researchers collected PA pressure data from patients twice daily for the entire 13-week study.
The EMBRACE HF (Empagliflozin Impact on Hemodynamics in Patients With Heart Failure) study enrolled patients with established heart failure, a CardioMEMS implant, and New York Heart Association class II-IV symptoms at any of eight U.S. centers. Patients averaged about 65 years old, and slightly more than half had class III disease, which denotes marked limitation of physical activity.
Despite the brief treatment period, patients who received empagliflozin showed other evidence of benefit including a trend toward improved quality of life scores, reduced levels of two different forms of brain natriuretic peptide, and significant weight loss, compared with controls, that averaged 2.4 kg.
The mechanism by which empagliflozin and other drugs in its class might lower PA filling pressures is unclear, but Dr. Kosiborod stressed that the consistent level of loop diuretic use during the study seems to rule out a diuretic effect from the SGLT2 inhibitor as having a role. A pulmonary vasculature effect is “much more likely,” perhaps mediated through modified endothelial function and vasodilation, he suggested.
EMBRACE HF was funded by Boehringer Ingelheim, the company that markets empagliflozin (Jardiance) along with Eli Lilly. Dr. Kosiborod has received research support and honoraria from Boehringer Ingelheim, and he has received honoraria from several other companies. Dr. Stevenson had no disclosures.
FROM HFSA 2020
Choosing Wisely: 10 practices to stop—or adopt—to reduce overuse in health care
When medical care is based on consistent, good-quality evidence, most physicians adopt it. However, not all care is well supported by the literature and may, in fact, be overused without offering benefit to patients. Choosing Wisely, at www.choosingwisely.org, is a health care initiative that highlights screening and testing recommendations from specialty societies in an effort to encourage patients and clinicians to talk about how to make high-value, effective health care decisions and avoid overuse. (See “Test and Tx overutilization: A bigger problem than you might think"1-3).
SIDEBAR
Test and Tx overutilization: A bigger problem than you might think
Care that isn’t backed up by the medical literature is adopted by some physicians and not adopted by others, leading to practice variations. Some variation is to be expected, since no 2 patients require exactly the same care, but substantial variations may be a clue to overuse.
A 2006 analysis of inpatient lab studies found that doctors ordered an average of 2.96 studies per patient per day, but only 29% of these tests (0.95 test/patient/day) contributed to management.1 A 2016 systematic review found more than 800 studies on overuse were published in a single year.2 One study of thyroid nodules followed almost 1000 patients with nodules as they underwent routine follow-up imaging. At the end of the study, 7 were found to have cancer, but of those, only 3 had enlarging or changing nodules that would have been detected with the follow-up imaging being studied. Three of the cancers were stable in size and 1 was found incidentally.3
Enabling physician and patient dialogue. The initiative began in 2010 when the American Board of Internal Medicine convened a panel of experts to identify low-value tests and therapies. Their list took the form of a “Top Five Things” that may not be high value in patient care, and it used language tailored to patients and physicians so that they could converse meaningfully. Physicians could use the evidence to make a clinical decision, and patients could feel empowered to ask informed questions about recommendations they received. The initiative has now expanded to include ways that health care systems can reduce low-value interventions.
Scope of participation. Since the first Choosing Wisely recommendations were published in 2013, more than 80 professional associations have contributed lists of their own. Professional societies participate voluntarily. The American Academy of Family Physicians (AAFP), Society of General Internal Medicine, and American Academy of Pediatrics (AAP) have contributed lists relevant to primary care. All Choosing Wisely recommendations can be searched or sorted by specialty organization. Recommendations are reviewed and revised regularly. If the evidence becomes conflicted or contradictory, recommendations are withdrawn.
Making meaningful improvements by Choosing Wisely
Several studies have shown that health care systems can implement Choosing Wisely recommendations to reduce overuse of unnecessary tests. A 2015 study examined the effect of applying a Choosing Wisely recommendation to reduce the use of continuous pulse oximetry in pediatric inpatients with asthma, wheezing, or bronchiolitis. The recommendation, from the Society of Hospital Medicine–Pediatric Hospital Medicine, advises against continuous pulse oximetry in children with acute respiratory illnesses unless the child is using supplemental oxygen.4 This study, done at the Cincinnati Children’s Hospital Medical Center, found that within 3 months of initiating a protocol on all general pediatrics floors, the average time on pulse oximetry after meeting clinical goals decreased from 10.7 hours to 3.1 hours. In addition, the percentage of patients who had their continuous pulse oximetry stopped within 2 hours of clinical stability (a goal time) increased from 25% to 46%.5
Patients are important drivers of health care utilization. A 2003 study showed that physicians are more likely to order referrals, tests, and prescriptions when patients ask for them, and that nearly 1 in 4 patients did so.6 A 2002 study found that physicians granted all but 3% of patient’s requests for orders or tests, and that fulfilling requests correlated with patient satisfaction in the specialty office studied (cardiology) but not in the primary care (internal medicine) office.7
From its inception, Choosing Wisely has considered patients as full partners in conversations about health care utilization. Choosing Wisely partners with Consumer Reports to create and disseminate plain-language summaries of recommendations. Community groups and physician organizations have also participated in implementation efforts. In 2018, Choosing Wisely secured a grant to expand outreach to diverse or underserved communities.
Choosing Wisely recommendations are not guidelines or mandates. They are intended to be evidence-based advice from a specialty society to its members and to patients about care that is often unnecessary. The goal is to create a conversation and not to eliminate these services from ever being offered or used.
Continue to: Improve your practice with these 10 primary care recommendations
Improve your practice with these 10 primary care recommendations
1 Avoid imaging studies in early acute low back pain without red flags.
Both the AAFP and the American Society of Anesthesiologists recommend against routine X-rays, magnetic resonance imaging, and computed tomography (CT) scans in the first 6 weeks of acute low back pain (LBP).8,9 The American College of Emergency Physicians (ACEP) recommends against routine lumbar spine imaging for emergency department (ED) patients.10 In all cases, imaging is indicated if the patient has any signs or symptoms of neurologic deficits or other indications, such as signs of spinal infection or fracture. However, as ACEP notes, diagnostic imaging does not typically help identify the cause of acute LBP, and when it does, it does not reduce the time to symptom improvement.10
2 Prescribe oral contraceptives on the basis of a medical history and a blood pressure measurement. No routine pelvic exam or other physical exam is necessary.
This AAFP recommendation11 is based on clinical practice guidelines from the American College of Obstetricians and Gynecologists (ACOG) and other research.12 The ACOG practice guideline supports provision of hormonal contraception without a pelvic exam, cervical cancer (Pap) testing, urine pregnancy testing, or testing for sexually transmitted infections. ACOG guidelines also support over-the-counter provision of hormonal contraceptives, including combined oral contraceptives.12
3 Stop recommending daily self-glucose monitoring for patients with diabetes who are not using insulin.
Both the AAFP and the Society for General Internal Medicine recommend against daily blood sugar checks for people who do not use insulin.13,14 A Cochrane review of 9 trials (3300 patients) found that after 6 months, hemoglobin A1C was reduced by 0.3% in people who checked their sugar daily compared with those who did not, but this difference was not significant after a year.15 Hypoglycemic episodes were more common in the “checking” group, and there were no differences in quality of life. A qualitative study found that blood sugar results had little impact on patients’ motivation to change behavior.16
4 Don’t screen for herpes simplex virus (HSV) infection in asymptomatic adults, even those who are pregnant.
This AAFP recommendation17 comes from a US Preventive Services Task Force (USPSTF) Grade D recommendation.18 Most people with positive HSV-2 serology have had an outbreak; even those who do not think they have had one will realize that they had the symptoms once they hear them described.18 With available tests, 1 in 2 positive results for HSV-2 among asymptomatic people will be a false-positive.18
There is no known cure, intervention, or reduction in transmission for infected patients who do not have symptoms.18 Also, serologically detected HSV-2 does not reliably predict genital herpes; and HSV-1 has been found to cause an increasing percentage of genital infection cases.18
Continue to: 5 Don't screen for testicular cancer in asymptomatic individuals
5 Don’t screen for testicular cancer in asymptomatic individuals.
This AAFP recommendation19 also comes from a USPSTF Grade D recommendation.20 A 2010 systematic review found no evidence to support screening of asymptomatic people with a physical exam or ultrasound. All available studies involved symptomatic patients.20
6 Stop recommending cough and cold medicines for children younger than 4 years.
The AAP recommends that clinicians discourage the use of any cough or cold medicine for children in this age-group.21 A 2008 study found that more than 7000 children annually presented to EDs for adverse events from cough and cold medicines.22 Previous studies found no benefit in reducing symptoms.23 In children older than 12 months, a Cochrane review found that honey has a modest benefit for cough in single-night trials.24
7 Avoid performing serum allergy panels.
The American Academy of Allergy, Asthma, and Immunology discourages the use of serum panel testing when patients present with allergy symptoms.25 A patient can have a strong positive immunoglobulin E (IgE) serum result to an allergen and have no clinical allergic symptoms or can have a weak positive serum result and a strong clinical reaction. Targeted skin or serum IgE testing—for example, testing for cashew allergy in a patient known to have had a reaction after eating one—is reasonable.26
8 Avoid routine electroencephalography (EEG), head CT, and carotid ultrasound as initial work-up for simple syncope in adults.
These recommendations, from the American Epilepsy Society,27 ACEP,28 American College of Physicians,29 and American Academy of Neurology (AAN),30 emphasize the low yield of routine work-ups for patients with simple syncope. The AAN notes that 40% of people will experience syncope during adulthood and most will not have carotid disease, which generally manifests with stroke-like symptoms rather than syncope. One study found that approximately 1 in 8 patients referred to an epilepsy clinic had neurocardiogenic syncope rather than epilepsy.31
EEGs have high false-negative and false-positive rates, and history-taking is a better tool with which to make a diagnosis. CT scans performed in the ED were found to contribute to the diagnosis of simple syncope in fewer than 2% of cases of syncope, compared with orthostatic blood pressure (25% of cases).32
Continue to: 9 Wait to refer children with umbilical hernias to pediatric surgery until they are 4 to 5 years of age
9 Wait to refer children with umbilical hernias to pediatric surgery until they are 4 to 5 years of age.
The AAP Section on Surgery offers evidence that the risk-benefit analysis strongly favors waiting on intervention.33 About 1 in 4 children will have an umbilical hernia, and about 85% of cases will resolve by age 5. The strangulation rate with umbilical hernias is very low, and although the risk of infection with surgery is likewise low, the risk of recurrence following surgery before the age of 4 is as high as 2.4%.34 The AAP Section on Surgery recommends against strapping or restraining the hernia, as well.
10 Avoid using appetite stimulants, such as megesterol, and high-calorie nutritional supplements to treat anorexia and cachexia in older adults.
Instead, the American Geriatrics Society recommends that physicians encourage caregivers to serve appealing food, provide support with eating, and remove barriers to appetite and nutrition.35 A Cochrane review showed that high-calorie supplements, such as Boost or Ensure, are associated with very modest weight gain—about 2% of weight—but are not associated with an increased life expectancy or improved quality of life.36
Prescription appetite stimulants are associated with adverse effects and yield inconsistent benefits in older adults. Megesterol, for example, was associated with headache, gastrointestinal adverse effects, insomnia, weakness, and fatigue. Mirtazapine is associated with sedation and fatigue.37
CORRESPONDENCE
Kathleen Rowland, MD, MS, Rush Copley Family Medicine Residency, Rush Medical College, 600 South Paulina, Kidston House Room 605, Chicago IL 60612; [email protected].
1. Miyakis S, Karamanof G, Liontos M, et al. Factors contributing to inappropriate ordering of tests in an academic medical department and the effect of an educational feedback strategy. Postgrad Med J. 2006;82:823-829.
2. Morgan DJ, Dhruva SS, Wright SM, et al. Update on medical overuse: a systematic review. JAMA Intern Med. 2016;176:1687-1692.
3. Durante C, Costante G, Lucisano G, et al. The natural history of benign thyroid nodules. JAMA. 2015;313:926-935.
4. Choosing Wisely. Society of Hospital Medicine—Pediatric hospital medicine. Don’t use continuous pulse oximetry routinely in children with acute respiratory illness unless they are on supplemental oxygen. www.choosingwisely.org/clinician-lists/society-hospital-medicine-pediatric-continuous-pulse-oximetry-in-children-with-acute-respiratory-illness/. Accessed September 28, 2020.
5. Schondelmeyer AC, Simmons JM, Statile AM, et al. Using quality improvement to reduce continuous pulse oximetry use in children with wheezing. Pediatrics. 2015;135:e1044-e1051.
6. Kravitz RL, Bell RA, Azari R, et al. Direct observation of requests for clinical services in office practice: what do patients want and do they get it? Arch Intern Med. 2003;163:1673-1681.
7. Kravitz RL, Bell RA, Franz CE, et al. Characterizing patient requests and physician responses in office practice. Health Serv Res. 2002;37:217-238.
8. Choosing Wisely. American Academy of Family Physicians. Don’t do imaging for low back pain within the first six weeks, unless red flags are present. www.choosingwisely.org/clinician-lists/american-academy-family-physicians-imaging-low-back-pain/. Accessed September 28, 2020.
9. Choosing Wisely. American Society of Anesthesiologists–Pain Medicine. Avoid imaging studies (MRI, CT or X-rays) for acute low back pain without specific indications. www.choosingwisely.org/clinician-lists/american-society-anesthesiologists-imaging-studies-for-acute-low-back-pain/. Accessed September 28, 2020.
10. Choosing Wisely. American College of Emergency Physicians. Avoid lumbar spine imaging in the emergency department for adults with non-traumatic back pain unless the patient has severe or progressive neurologic deficits or is suspected of having a serious underlying condition (such as vertebral infection, cauda equina syndrome, or cancer with bony metastasis). www.choosingwisely.org/clinician-lists/acep-lumbar-spine-imaging-in-the-ed/. Accessed September 28, 2020.
11. Choosing Wisely. American Academy of Family Physicians. Don’t require a pelvic exam or other physical exam to prescribe oral contraceptive medications. www.choosingwisely.org/clinician-lists/american-academy-family-physicians-pelvic-or-physical-exams-to-prescribe-oral-contraceptives/. Accessed September 28, 2020.
12. Over-the-counter access to hormonal contraception. ACOG Committee Opinion, Number 788. Obstet Gynecol. 2019;134:e96-e105. https://journals.lww.com/greenjournal/Fulltext/2019/10000/Over_the_Counter_Access_to_Hormonal_Contraception_.46.aspx. Accessed September 28, 2020.
13. Choosing Wisely. American Academy of Family Physicians. Don’t routinely recommend daily home glucose monitoring for patients who have Type 2 diabetes mellitus and are not using insulin. www.choosingwisely.org/clinician-lists/aafp-daily-home-glucose-monitoring-for-patients-with-type-2-diabetes. Accessed September 28, 2020.
14. Choosing Wisely. Society of General Internal Medicine. Don’t recommend daily home finger glucose testing in patients with Type 2 diabetes mellitus not using insulin. www.choosingwisely.org/clinician-lists/society-general-internal-medicine-daily-home-finger-glucose-testing-type-2-diabetes-mellitus/. Accessed September 28, 2020.
15. Malanda UL, Welschen LM, Riphagen II, et al. Self‐monitoring of blood glucose in patients with type 2 diabetes mellitus who are not using insulin. Cochrane Database Syst Rev. 2012(1):CD005060.
16. Peel E, Douglas M, Lawton J. Self monitoring of blood glucose in type 2 diabetes: longitudinal qualitative study of patients’ perspectives. BMJ. 2007;335:493.
17. Choosing Wisely. American Academy of Family Physicians. Don’t screen for genital herpes simplex virus infection (HSV) in asymptomatic adults, including pregnant women. www.choosingwisely.org/clinician-lists/aafp-genital-herpes-screening-in-asymptomatic-adults/. Accessed September 28, 2020.
18. Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Serologic screening for genital herpes infection: US Preventive Services Task Force recommendation statement. JAMA. 2016;316:2525-2530.
19. Choosing Wisely. American Academy of Family Physicians. Don’t screen for testicular cancer in asymptomatic adolescent and adult males. www.choosingwisely.org/clinician-lists/aafp-testicular-cancer-screening-in-asymptomatic-adolescent-and-adult-men/. Accessed September 28, 2020.
20. Lin K, Sharangpani R. Screening for testicular cancer: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2010;153:396-399.
21. Choosing Wisely. American Academy of Pediatrics. Cough and cold medicines should not be prescribed, recommended or used for respiratory illnesses in young children. www.choosingwisely.org/clinician-lists/american-academy-pediatrics-cough-and-cold-medicines-for-children-under-four/. Accessed September 28, 2020.
22. Schaefer MK, Shehab N, Cohen AL, et al. Adverse events from cough and cold medications in children. Pediatrics. 2008;121:783-787.
23. Carr BC. Efficacy, abuse, and toxicity of over-the-counter cough and cold medicines in the pediatric population. Curr Opin Pediatr. 2006;18:184-188.
24. Oduwole O, Udoh EE, Oyo‐Ita A, et al. Honey for acute cough in children. Cochrane Database Syst Rev. 2018(4):CD007094.
25. Choosing Wisely. American Academy of Allergy, Asthma & Immunology. Don’t perform unproven diagnostic tests, such as immunoglobulin G(lgG) testing or an indiscriminate battery of immunoglobulin E(lgE) tests, in the evaluation of allergy. www.choosingwisely.org/clinician-lists/american-academy-allergy-asthma-immunology-diagnostic-tests-for-allergy-evaluation/. Accessed September 28, 2020.
26. Cox L, Williams B, Sicherer S, et al. Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology Specific IgE Test Task Force. Ann Allergy Asthma Immunol. 2008;101:580-592.
27. Choosing Wisely. American Epilepsy Society. Do not routinely order electroencephalogram (EEG) as part of initial syncope work-up. www.choosingwisely.org/clinician-lists/aes-eeg-as-part-of-initial-syncope-work-up/. Accessed September 28, 2020.
28. Choosing Wisely. American College of Emergency Physicians. Avoid CT of the head in asymptomatic adult patients in the emergency department with syncope, insignificant trauma and a normal neurological evaluation. www.choosingwisely.org/clinician-lists/acep-avoid-head-ct-for-asymptomatic-adults-with-syncope/. Accessed September 28, 2020.
29. Choosing Wisely. American College of Physicians. In the evaluation of simple syncope and a normal neurological examination, don’t obtain brain imaging studies (CT or MRI). www.choosingwisely.org/clinician-lists/american-college-physicians-brain-imaging-to-evaluate-simple-syncope/. Accessed September 28, 2020.
30. Choosing Wisely. American Academy of Neurology. Don’t perform imaging of the carotid arteries for simple syncope without other neurologic symptoms. www.choosingwisely.org/clinician-lists/american-academy-neurology-carotid-artery-imaging-for-simple-syncope/. Accessed September 28, 2020.
31. Josephson CB, Rahey S, Sadler RM. Neurocardiogenic syncope: frequency and consequences of its misdiagnosis as epilepsy. Can J Neurol Sci. 2007;34:221-224.
32. Mendu ML, McAvay G, Lampert R, et al. Yield of diagnostic tests in evaluating syncopal episodes in older patients. Arch Intern Med. 2009;169:1299-1305.
33. Choosing Wisely. American Academy of Pediatrics–Section on Surgery. Avoid referring most children with umbilical hernias to a pediatric surgeon until around age 4-5 years. www.choosingwisely.org/clinician-lists/aap-sosu-avoid-surgery-referral-for-umbilical-hernias-until-age-4-5/. Accessed September 28, 2020.
34. Antonoff MB, Kreykes NS, Saltzman DA, et al. American Academy of Pediatrics Section on Surgery hernia survey revisited. J Pediatr Surg. 2005;40:1009-1014.
35. Choosing Wisely. American Geriatrics Society. Avoid using prescription appetite stimulants or high-calorie supplements for treatment of anorexia or cachexia in older adults; instead, optimize social supports, discontinue medications that may interfere with eating, provide appealing food and feeding assistance, and clarify patient goals and expectations. www.choosingwisely.org/clinician-lists/american-geriatrics-society-prescription-appetite-stimulants-to-treat-anorexia-cachexia-in-elderly/. Accessed September 28, 2020.
36. Milne AC, Potter J, Vivanti A, et al. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Sys Rev. 2009(2):CD003288.
37. Fox CB, Treadway AK, Blaszczyk AT, et al. Megestrol acetate and mirtazapine for the treatment of unplanned weight loss in the elderly. Pharmacotherapy. 2009;29:383-397.
When medical care is based on consistent, good-quality evidence, most physicians adopt it. However, not all care is well supported by the literature and may, in fact, be overused without offering benefit to patients. Choosing Wisely, at www.choosingwisely.org, is a health care initiative that highlights screening and testing recommendations from specialty societies in an effort to encourage patients and clinicians to talk about how to make high-value, effective health care decisions and avoid overuse. (See “Test and Tx overutilization: A bigger problem than you might think"1-3).
SIDEBAR
Test and Tx overutilization: A bigger problem than you might think
Care that isn’t backed up by the medical literature is adopted by some physicians and not adopted by others, leading to practice variations. Some variation is to be expected, since no 2 patients require exactly the same care, but substantial variations may be a clue to overuse.
A 2006 analysis of inpatient lab studies found that doctors ordered an average of 2.96 studies per patient per day, but only 29% of these tests (0.95 test/patient/day) contributed to management.1 A 2016 systematic review found more than 800 studies on overuse were published in a single year.2 One study of thyroid nodules followed almost 1000 patients with nodules as they underwent routine follow-up imaging. At the end of the study, 7 were found to have cancer, but of those, only 3 had enlarging or changing nodules that would have been detected with the follow-up imaging being studied. Three of the cancers were stable in size and 1 was found incidentally.3
Enabling physician and patient dialogue. The initiative began in 2010 when the American Board of Internal Medicine convened a panel of experts to identify low-value tests and therapies. Their list took the form of a “Top Five Things” that may not be high value in patient care, and it used language tailored to patients and physicians so that they could converse meaningfully. Physicians could use the evidence to make a clinical decision, and patients could feel empowered to ask informed questions about recommendations they received. The initiative has now expanded to include ways that health care systems can reduce low-value interventions.
Scope of participation. Since the first Choosing Wisely recommendations were published in 2013, more than 80 professional associations have contributed lists of their own. Professional societies participate voluntarily. The American Academy of Family Physicians (AAFP), Society of General Internal Medicine, and American Academy of Pediatrics (AAP) have contributed lists relevant to primary care. All Choosing Wisely recommendations can be searched or sorted by specialty organization. Recommendations are reviewed and revised regularly. If the evidence becomes conflicted or contradictory, recommendations are withdrawn.
Making meaningful improvements by Choosing Wisely
Several studies have shown that health care systems can implement Choosing Wisely recommendations to reduce overuse of unnecessary tests. A 2015 study examined the effect of applying a Choosing Wisely recommendation to reduce the use of continuous pulse oximetry in pediatric inpatients with asthma, wheezing, or bronchiolitis. The recommendation, from the Society of Hospital Medicine–Pediatric Hospital Medicine, advises against continuous pulse oximetry in children with acute respiratory illnesses unless the child is using supplemental oxygen.4 This study, done at the Cincinnati Children’s Hospital Medical Center, found that within 3 months of initiating a protocol on all general pediatrics floors, the average time on pulse oximetry after meeting clinical goals decreased from 10.7 hours to 3.1 hours. In addition, the percentage of patients who had their continuous pulse oximetry stopped within 2 hours of clinical stability (a goal time) increased from 25% to 46%.5
Patients are important drivers of health care utilization. A 2003 study showed that physicians are more likely to order referrals, tests, and prescriptions when patients ask for them, and that nearly 1 in 4 patients did so.6 A 2002 study found that physicians granted all but 3% of patient’s requests for orders or tests, and that fulfilling requests correlated with patient satisfaction in the specialty office studied (cardiology) but not in the primary care (internal medicine) office.7
From its inception, Choosing Wisely has considered patients as full partners in conversations about health care utilization. Choosing Wisely partners with Consumer Reports to create and disseminate plain-language summaries of recommendations. Community groups and physician organizations have also participated in implementation efforts. In 2018, Choosing Wisely secured a grant to expand outreach to diverse or underserved communities.
Choosing Wisely recommendations are not guidelines or mandates. They are intended to be evidence-based advice from a specialty society to its members and to patients about care that is often unnecessary. The goal is to create a conversation and not to eliminate these services from ever being offered or used.
Continue to: Improve your practice with these 10 primary care recommendations
Improve your practice with these 10 primary care recommendations
1 Avoid imaging studies in early acute low back pain without red flags.
Both the AAFP and the American Society of Anesthesiologists recommend against routine X-rays, magnetic resonance imaging, and computed tomography (CT) scans in the first 6 weeks of acute low back pain (LBP).8,9 The American College of Emergency Physicians (ACEP) recommends against routine lumbar spine imaging for emergency department (ED) patients.10 In all cases, imaging is indicated if the patient has any signs or symptoms of neurologic deficits or other indications, such as signs of spinal infection or fracture. However, as ACEP notes, diagnostic imaging does not typically help identify the cause of acute LBP, and when it does, it does not reduce the time to symptom improvement.10
2 Prescribe oral contraceptives on the basis of a medical history and a blood pressure measurement. No routine pelvic exam or other physical exam is necessary.
This AAFP recommendation11 is based on clinical practice guidelines from the American College of Obstetricians and Gynecologists (ACOG) and other research.12 The ACOG practice guideline supports provision of hormonal contraception without a pelvic exam, cervical cancer (Pap) testing, urine pregnancy testing, or testing for sexually transmitted infections. ACOG guidelines also support over-the-counter provision of hormonal contraceptives, including combined oral contraceptives.12
3 Stop recommending daily self-glucose monitoring for patients with diabetes who are not using insulin.
Both the AAFP and the Society for General Internal Medicine recommend against daily blood sugar checks for people who do not use insulin.13,14 A Cochrane review of 9 trials (3300 patients) found that after 6 months, hemoglobin A1C was reduced by 0.3% in people who checked their sugar daily compared with those who did not, but this difference was not significant after a year.15 Hypoglycemic episodes were more common in the “checking” group, and there were no differences in quality of life. A qualitative study found that blood sugar results had little impact on patients’ motivation to change behavior.16
4 Don’t screen for herpes simplex virus (HSV) infection in asymptomatic adults, even those who are pregnant.
This AAFP recommendation17 comes from a US Preventive Services Task Force (USPSTF) Grade D recommendation.18 Most people with positive HSV-2 serology have had an outbreak; even those who do not think they have had one will realize that they had the symptoms once they hear them described.18 With available tests, 1 in 2 positive results for HSV-2 among asymptomatic people will be a false-positive.18
There is no known cure, intervention, or reduction in transmission for infected patients who do not have symptoms.18 Also, serologically detected HSV-2 does not reliably predict genital herpes; and HSV-1 has been found to cause an increasing percentage of genital infection cases.18
Continue to: 5 Don't screen for testicular cancer in asymptomatic individuals
5 Don’t screen for testicular cancer in asymptomatic individuals.
This AAFP recommendation19 also comes from a USPSTF Grade D recommendation.20 A 2010 systematic review found no evidence to support screening of asymptomatic people with a physical exam or ultrasound. All available studies involved symptomatic patients.20
6 Stop recommending cough and cold medicines for children younger than 4 years.
The AAP recommends that clinicians discourage the use of any cough or cold medicine for children in this age-group.21 A 2008 study found that more than 7000 children annually presented to EDs for adverse events from cough and cold medicines.22 Previous studies found no benefit in reducing symptoms.23 In children older than 12 months, a Cochrane review found that honey has a modest benefit for cough in single-night trials.24
7 Avoid performing serum allergy panels.
The American Academy of Allergy, Asthma, and Immunology discourages the use of serum panel testing when patients present with allergy symptoms.25 A patient can have a strong positive immunoglobulin E (IgE) serum result to an allergen and have no clinical allergic symptoms or can have a weak positive serum result and a strong clinical reaction. Targeted skin or serum IgE testing—for example, testing for cashew allergy in a patient known to have had a reaction after eating one—is reasonable.26
8 Avoid routine electroencephalography (EEG), head CT, and carotid ultrasound as initial work-up for simple syncope in adults.
These recommendations, from the American Epilepsy Society,27 ACEP,28 American College of Physicians,29 and American Academy of Neurology (AAN),30 emphasize the low yield of routine work-ups for patients with simple syncope. The AAN notes that 40% of people will experience syncope during adulthood and most will not have carotid disease, which generally manifests with stroke-like symptoms rather than syncope. One study found that approximately 1 in 8 patients referred to an epilepsy clinic had neurocardiogenic syncope rather than epilepsy.31
EEGs have high false-negative and false-positive rates, and history-taking is a better tool with which to make a diagnosis. CT scans performed in the ED were found to contribute to the diagnosis of simple syncope in fewer than 2% of cases of syncope, compared with orthostatic blood pressure (25% of cases).32
Continue to: 9 Wait to refer children with umbilical hernias to pediatric surgery until they are 4 to 5 years of age
9 Wait to refer children with umbilical hernias to pediatric surgery until they are 4 to 5 years of age.
The AAP Section on Surgery offers evidence that the risk-benefit analysis strongly favors waiting on intervention.33 About 1 in 4 children will have an umbilical hernia, and about 85% of cases will resolve by age 5. The strangulation rate with umbilical hernias is very low, and although the risk of infection with surgery is likewise low, the risk of recurrence following surgery before the age of 4 is as high as 2.4%.34 The AAP Section on Surgery recommends against strapping or restraining the hernia, as well.
10 Avoid using appetite stimulants, such as megesterol, and high-calorie nutritional supplements to treat anorexia and cachexia in older adults.
Instead, the American Geriatrics Society recommends that physicians encourage caregivers to serve appealing food, provide support with eating, and remove barriers to appetite and nutrition.35 A Cochrane review showed that high-calorie supplements, such as Boost or Ensure, are associated with very modest weight gain—about 2% of weight—but are not associated with an increased life expectancy or improved quality of life.36
Prescription appetite stimulants are associated with adverse effects and yield inconsistent benefits in older adults. Megesterol, for example, was associated with headache, gastrointestinal adverse effects, insomnia, weakness, and fatigue. Mirtazapine is associated with sedation and fatigue.37
CORRESPONDENCE
Kathleen Rowland, MD, MS, Rush Copley Family Medicine Residency, Rush Medical College, 600 South Paulina, Kidston House Room 605, Chicago IL 60612; [email protected].
When medical care is based on consistent, good-quality evidence, most physicians adopt it. However, not all care is well supported by the literature and may, in fact, be overused without offering benefit to patients. Choosing Wisely, at www.choosingwisely.org, is a health care initiative that highlights screening and testing recommendations from specialty societies in an effort to encourage patients and clinicians to talk about how to make high-value, effective health care decisions and avoid overuse. (See “Test and Tx overutilization: A bigger problem than you might think"1-3).
SIDEBAR
Test and Tx overutilization: A bigger problem than you might think
Care that isn’t backed up by the medical literature is adopted by some physicians and not adopted by others, leading to practice variations. Some variation is to be expected, since no 2 patients require exactly the same care, but substantial variations may be a clue to overuse.
A 2006 analysis of inpatient lab studies found that doctors ordered an average of 2.96 studies per patient per day, but only 29% of these tests (0.95 test/patient/day) contributed to management.1 A 2016 systematic review found more than 800 studies on overuse were published in a single year.2 One study of thyroid nodules followed almost 1000 patients with nodules as they underwent routine follow-up imaging. At the end of the study, 7 were found to have cancer, but of those, only 3 had enlarging or changing nodules that would have been detected with the follow-up imaging being studied. Three of the cancers were stable in size and 1 was found incidentally.3
Enabling physician and patient dialogue. The initiative began in 2010 when the American Board of Internal Medicine convened a panel of experts to identify low-value tests and therapies. Their list took the form of a “Top Five Things” that may not be high value in patient care, and it used language tailored to patients and physicians so that they could converse meaningfully. Physicians could use the evidence to make a clinical decision, and patients could feel empowered to ask informed questions about recommendations they received. The initiative has now expanded to include ways that health care systems can reduce low-value interventions.
Scope of participation. Since the first Choosing Wisely recommendations were published in 2013, more than 80 professional associations have contributed lists of their own. Professional societies participate voluntarily. The American Academy of Family Physicians (AAFP), Society of General Internal Medicine, and American Academy of Pediatrics (AAP) have contributed lists relevant to primary care. All Choosing Wisely recommendations can be searched or sorted by specialty organization. Recommendations are reviewed and revised regularly. If the evidence becomes conflicted or contradictory, recommendations are withdrawn.
Making meaningful improvements by Choosing Wisely
Several studies have shown that health care systems can implement Choosing Wisely recommendations to reduce overuse of unnecessary tests. A 2015 study examined the effect of applying a Choosing Wisely recommendation to reduce the use of continuous pulse oximetry in pediatric inpatients with asthma, wheezing, or bronchiolitis. The recommendation, from the Society of Hospital Medicine–Pediatric Hospital Medicine, advises against continuous pulse oximetry in children with acute respiratory illnesses unless the child is using supplemental oxygen.4 This study, done at the Cincinnati Children’s Hospital Medical Center, found that within 3 months of initiating a protocol on all general pediatrics floors, the average time on pulse oximetry after meeting clinical goals decreased from 10.7 hours to 3.1 hours. In addition, the percentage of patients who had their continuous pulse oximetry stopped within 2 hours of clinical stability (a goal time) increased from 25% to 46%.5
Patients are important drivers of health care utilization. A 2003 study showed that physicians are more likely to order referrals, tests, and prescriptions when patients ask for them, and that nearly 1 in 4 patients did so.6 A 2002 study found that physicians granted all but 3% of patient’s requests for orders or tests, and that fulfilling requests correlated with patient satisfaction in the specialty office studied (cardiology) but not in the primary care (internal medicine) office.7
From its inception, Choosing Wisely has considered patients as full partners in conversations about health care utilization. Choosing Wisely partners with Consumer Reports to create and disseminate plain-language summaries of recommendations. Community groups and physician organizations have also participated in implementation efforts. In 2018, Choosing Wisely secured a grant to expand outreach to diverse or underserved communities.
Choosing Wisely recommendations are not guidelines or mandates. They are intended to be evidence-based advice from a specialty society to its members and to patients about care that is often unnecessary. The goal is to create a conversation and not to eliminate these services from ever being offered or used.
Continue to: Improve your practice with these 10 primary care recommendations
Improve your practice with these 10 primary care recommendations
1 Avoid imaging studies in early acute low back pain without red flags.
Both the AAFP and the American Society of Anesthesiologists recommend against routine X-rays, magnetic resonance imaging, and computed tomography (CT) scans in the first 6 weeks of acute low back pain (LBP).8,9 The American College of Emergency Physicians (ACEP) recommends against routine lumbar spine imaging for emergency department (ED) patients.10 In all cases, imaging is indicated if the patient has any signs or symptoms of neurologic deficits or other indications, such as signs of spinal infection or fracture. However, as ACEP notes, diagnostic imaging does not typically help identify the cause of acute LBP, and when it does, it does not reduce the time to symptom improvement.10
2 Prescribe oral contraceptives on the basis of a medical history and a blood pressure measurement. No routine pelvic exam or other physical exam is necessary.
This AAFP recommendation11 is based on clinical practice guidelines from the American College of Obstetricians and Gynecologists (ACOG) and other research.12 The ACOG practice guideline supports provision of hormonal contraception without a pelvic exam, cervical cancer (Pap) testing, urine pregnancy testing, or testing for sexually transmitted infections. ACOG guidelines also support over-the-counter provision of hormonal contraceptives, including combined oral contraceptives.12
3 Stop recommending daily self-glucose monitoring for patients with diabetes who are not using insulin.
Both the AAFP and the Society for General Internal Medicine recommend against daily blood sugar checks for people who do not use insulin.13,14 A Cochrane review of 9 trials (3300 patients) found that after 6 months, hemoglobin A1C was reduced by 0.3% in people who checked their sugar daily compared with those who did not, but this difference was not significant after a year.15 Hypoglycemic episodes were more common in the “checking” group, and there were no differences in quality of life. A qualitative study found that blood sugar results had little impact on patients’ motivation to change behavior.16
4 Don’t screen for herpes simplex virus (HSV) infection in asymptomatic adults, even those who are pregnant.
This AAFP recommendation17 comes from a US Preventive Services Task Force (USPSTF) Grade D recommendation.18 Most people with positive HSV-2 serology have had an outbreak; even those who do not think they have had one will realize that they had the symptoms once they hear them described.18 With available tests, 1 in 2 positive results for HSV-2 among asymptomatic people will be a false-positive.18
There is no known cure, intervention, or reduction in transmission for infected patients who do not have symptoms.18 Also, serologically detected HSV-2 does not reliably predict genital herpes; and HSV-1 has been found to cause an increasing percentage of genital infection cases.18
Continue to: 5 Don't screen for testicular cancer in asymptomatic individuals
5 Don’t screen for testicular cancer in asymptomatic individuals.
This AAFP recommendation19 also comes from a USPSTF Grade D recommendation.20 A 2010 systematic review found no evidence to support screening of asymptomatic people with a physical exam or ultrasound. All available studies involved symptomatic patients.20
6 Stop recommending cough and cold medicines for children younger than 4 years.
The AAP recommends that clinicians discourage the use of any cough or cold medicine for children in this age-group.21 A 2008 study found that more than 7000 children annually presented to EDs for adverse events from cough and cold medicines.22 Previous studies found no benefit in reducing symptoms.23 In children older than 12 months, a Cochrane review found that honey has a modest benefit for cough in single-night trials.24
7 Avoid performing serum allergy panels.
The American Academy of Allergy, Asthma, and Immunology discourages the use of serum panel testing when patients present with allergy symptoms.25 A patient can have a strong positive immunoglobulin E (IgE) serum result to an allergen and have no clinical allergic symptoms or can have a weak positive serum result and a strong clinical reaction. Targeted skin or serum IgE testing—for example, testing for cashew allergy in a patient known to have had a reaction after eating one—is reasonable.26
8 Avoid routine electroencephalography (EEG), head CT, and carotid ultrasound as initial work-up for simple syncope in adults.
These recommendations, from the American Epilepsy Society,27 ACEP,28 American College of Physicians,29 and American Academy of Neurology (AAN),30 emphasize the low yield of routine work-ups for patients with simple syncope. The AAN notes that 40% of people will experience syncope during adulthood and most will not have carotid disease, which generally manifests with stroke-like symptoms rather than syncope. One study found that approximately 1 in 8 patients referred to an epilepsy clinic had neurocardiogenic syncope rather than epilepsy.31
EEGs have high false-negative and false-positive rates, and history-taking is a better tool with which to make a diagnosis. CT scans performed in the ED were found to contribute to the diagnosis of simple syncope in fewer than 2% of cases of syncope, compared with orthostatic blood pressure (25% of cases).32
Continue to: 9 Wait to refer children with umbilical hernias to pediatric surgery until they are 4 to 5 years of age
9 Wait to refer children with umbilical hernias to pediatric surgery until they are 4 to 5 years of age.
The AAP Section on Surgery offers evidence that the risk-benefit analysis strongly favors waiting on intervention.33 About 1 in 4 children will have an umbilical hernia, and about 85% of cases will resolve by age 5. The strangulation rate with umbilical hernias is very low, and although the risk of infection with surgery is likewise low, the risk of recurrence following surgery before the age of 4 is as high as 2.4%.34 The AAP Section on Surgery recommends against strapping or restraining the hernia, as well.
10 Avoid using appetite stimulants, such as megesterol, and high-calorie nutritional supplements to treat anorexia and cachexia in older adults.
Instead, the American Geriatrics Society recommends that physicians encourage caregivers to serve appealing food, provide support with eating, and remove barriers to appetite and nutrition.35 A Cochrane review showed that high-calorie supplements, such as Boost or Ensure, are associated with very modest weight gain—about 2% of weight—but are not associated with an increased life expectancy or improved quality of life.36
Prescription appetite stimulants are associated with adverse effects and yield inconsistent benefits in older adults. Megesterol, for example, was associated with headache, gastrointestinal adverse effects, insomnia, weakness, and fatigue. Mirtazapine is associated with sedation and fatigue.37
CORRESPONDENCE
Kathleen Rowland, MD, MS, Rush Copley Family Medicine Residency, Rush Medical College, 600 South Paulina, Kidston House Room 605, Chicago IL 60612; [email protected].
1. Miyakis S, Karamanof G, Liontos M, et al. Factors contributing to inappropriate ordering of tests in an academic medical department and the effect of an educational feedback strategy. Postgrad Med J. 2006;82:823-829.
2. Morgan DJ, Dhruva SS, Wright SM, et al. Update on medical overuse: a systematic review. JAMA Intern Med. 2016;176:1687-1692.
3. Durante C, Costante G, Lucisano G, et al. The natural history of benign thyroid nodules. JAMA. 2015;313:926-935.
4. Choosing Wisely. Society of Hospital Medicine—Pediatric hospital medicine. Don’t use continuous pulse oximetry routinely in children with acute respiratory illness unless they are on supplemental oxygen. www.choosingwisely.org/clinician-lists/society-hospital-medicine-pediatric-continuous-pulse-oximetry-in-children-with-acute-respiratory-illness/. Accessed September 28, 2020.
5. Schondelmeyer AC, Simmons JM, Statile AM, et al. Using quality improvement to reduce continuous pulse oximetry use in children with wheezing. Pediatrics. 2015;135:e1044-e1051.
6. Kravitz RL, Bell RA, Azari R, et al. Direct observation of requests for clinical services in office practice: what do patients want and do they get it? Arch Intern Med. 2003;163:1673-1681.
7. Kravitz RL, Bell RA, Franz CE, et al. Characterizing patient requests and physician responses in office practice. Health Serv Res. 2002;37:217-238.
8. Choosing Wisely. American Academy of Family Physicians. Don’t do imaging for low back pain within the first six weeks, unless red flags are present. www.choosingwisely.org/clinician-lists/american-academy-family-physicians-imaging-low-back-pain/. Accessed September 28, 2020.
9. Choosing Wisely. American Society of Anesthesiologists–Pain Medicine. Avoid imaging studies (MRI, CT or X-rays) for acute low back pain without specific indications. www.choosingwisely.org/clinician-lists/american-society-anesthesiologists-imaging-studies-for-acute-low-back-pain/. Accessed September 28, 2020.
10. Choosing Wisely. American College of Emergency Physicians. Avoid lumbar spine imaging in the emergency department for adults with non-traumatic back pain unless the patient has severe or progressive neurologic deficits or is suspected of having a serious underlying condition (such as vertebral infection, cauda equina syndrome, or cancer with bony metastasis). www.choosingwisely.org/clinician-lists/acep-lumbar-spine-imaging-in-the-ed/. Accessed September 28, 2020.
11. Choosing Wisely. American Academy of Family Physicians. Don’t require a pelvic exam or other physical exam to prescribe oral contraceptive medications. www.choosingwisely.org/clinician-lists/american-academy-family-physicians-pelvic-or-physical-exams-to-prescribe-oral-contraceptives/. Accessed September 28, 2020.
12. Over-the-counter access to hormonal contraception. ACOG Committee Opinion, Number 788. Obstet Gynecol. 2019;134:e96-e105. https://journals.lww.com/greenjournal/Fulltext/2019/10000/Over_the_Counter_Access_to_Hormonal_Contraception_.46.aspx. Accessed September 28, 2020.
13. Choosing Wisely. American Academy of Family Physicians. Don’t routinely recommend daily home glucose monitoring for patients who have Type 2 diabetes mellitus and are not using insulin. www.choosingwisely.org/clinician-lists/aafp-daily-home-glucose-monitoring-for-patients-with-type-2-diabetes. Accessed September 28, 2020.
14. Choosing Wisely. Society of General Internal Medicine. Don’t recommend daily home finger glucose testing in patients with Type 2 diabetes mellitus not using insulin. www.choosingwisely.org/clinician-lists/society-general-internal-medicine-daily-home-finger-glucose-testing-type-2-diabetes-mellitus/. Accessed September 28, 2020.
15. Malanda UL, Welschen LM, Riphagen II, et al. Self‐monitoring of blood glucose in patients with type 2 diabetes mellitus who are not using insulin. Cochrane Database Syst Rev. 2012(1):CD005060.
16. Peel E, Douglas M, Lawton J. Self monitoring of blood glucose in type 2 diabetes: longitudinal qualitative study of patients’ perspectives. BMJ. 2007;335:493.
17. Choosing Wisely. American Academy of Family Physicians. Don’t screen for genital herpes simplex virus infection (HSV) in asymptomatic adults, including pregnant women. www.choosingwisely.org/clinician-lists/aafp-genital-herpes-screening-in-asymptomatic-adults/. Accessed September 28, 2020.
18. Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Serologic screening for genital herpes infection: US Preventive Services Task Force recommendation statement. JAMA. 2016;316:2525-2530.
19. Choosing Wisely. American Academy of Family Physicians. Don’t screen for testicular cancer in asymptomatic adolescent and adult males. www.choosingwisely.org/clinician-lists/aafp-testicular-cancer-screening-in-asymptomatic-adolescent-and-adult-men/. Accessed September 28, 2020.
20. Lin K, Sharangpani R. Screening for testicular cancer: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2010;153:396-399.
21. Choosing Wisely. American Academy of Pediatrics. Cough and cold medicines should not be prescribed, recommended or used for respiratory illnesses in young children. www.choosingwisely.org/clinician-lists/american-academy-pediatrics-cough-and-cold-medicines-for-children-under-four/. Accessed September 28, 2020.
22. Schaefer MK, Shehab N, Cohen AL, et al. Adverse events from cough and cold medications in children. Pediatrics. 2008;121:783-787.
23. Carr BC. Efficacy, abuse, and toxicity of over-the-counter cough and cold medicines in the pediatric population. Curr Opin Pediatr. 2006;18:184-188.
24. Oduwole O, Udoh EE, Oyo‐Ita A, et al. Honey for acute cough in children. Cochrane Database Syst Rev. 2018(4):CD007094.
25. Choosing Wisely. American Academy of Allergy, Asthma & Immunology. Don’t perform unproven diagnostic tests, such as immunoglobulin G(lgG) testing or an indiscriminate battery of immunoglobulin E(lgE) tests, in the evaluation of allergy. www.choosingwisely.org/clinician-lists/american-academy-allergy-asthma-immunology-diagnostic-tests-for-allergy-evaluation/. Accessed September 28, 2020.
26. Cox L, Williams B, Sicherer S, et al. Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology Specific IgE Test Task Force. Ann Allergy Asthma Immunol. 2008;101:580-592.
27. Choosing Wisely. American Epilepsy Society. Do not routinely order electroencephalogram (EEG) as part of initial syncope work-up. www.choosingwisely.org/clinician-lists/aes-eeg-as-part-of-initial-syncope-work-up/. Accessed September 28, 2020.
28. Choosing Wisely. American College of Emergency Physicians. Avoid CT of the head in asymptomatic adult patients in the emergency department with syncope, insignificant trauma and a normal neurological evaluation. www.choosingwisely.org/clinician-lists/acep-avoid-head-ct-for-asymptomatic-adults-with-syncope/. Accessed September 28, 2020.
29. Choosing Wisely. American College of Physicians. In the evaluation of simple syncope and a normal neurological examination, don’t obtain brain imaging studies (CT or MRI). www.choosingwisely.org/clinician-lists/american-college-physicians-brain-imaging-to-evaluate-simple-syncope/. Accessed September 28, 2020.
30. Choosing Wisely. American Academy of Neurology. Don’t perform imaging of the carotid arteries for simple syncope without other neurologic symptoms. www.choosingwisely.org/clinician-lists/american-academy-neurology-carotid-artery-imaging-for-simple-syncope/. Accessed September 28, 2020.
31. Josephson CB, Rahey S, Sadler RM. Neurocardiogenic syncope: frequency and consequences of its misdiagnosis as epilepsy. Can J Neurol Sci. 2007;34:221-224.
32. Mendu ML, McAvay G, Lampert R, et al. Yield of diagnostic tests in evaluating syncopal episodes in older patients. Arch Intern Med. 2009;169:1299-1305.
33. Choosing Wisely. American Academy of Pediatrics–Section on Surgery. Avoid referring most children with umbilical hernias to a pediatric surgeon until around age 4-5 years. www.choosingwisely.org/clinician-lists/aap-sosu-avoid-surgery-referral-for-umbilical-hernias-until-age-4-5/. Accessed September 28, 2020.
34. Antonoff MB, Kreykes NS, Saltzman DA, et al. American Academy of Pediatrics Section on Surgery hernia survey revisited. J Pediatr Surg. 2005;40:1009-1014.
35. Choosing Wisely. American Geriatrics Society. Avoid using prescription appetite stimulants or high-calorie supplements for treatment of anorexia or cachexia in older adults; instead, optimize social supports, discontinue medications that may interfere with eating, provide appealing food and feeding assistance, and clarify patient goals and expectations. www.choosingwisely.org/clinician-lists/american-geriatrics-society-prescription-appetite-stimulants-to-treat-anorexia-cachexia-in-elderly/. Accessed September 28, 2020.
36. Milne AC, Potter J, Vivanti A, et al. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Sys Rev. 2009(2):CD003288.
37. Fox CB, Treadway AK, Blaszczyk AT, et al. Megestrol acetate and mirtazapine for the treatment of unplanned weight loss in the elderly. Pharmacotherapy. 2009;29:383-397.
1. Miyakis S, Karamanof G, Liontos M, et al. Factors contributing to inappropriate ordering of tests in an academic medical department and the effect of an educational feedback strategy. Postgrad Med J. 2006;82:823-829.
2. Morgan DJ, Dhruva SS, Wright SM, et al. Update on medical overuse: a systematic review. JAMA Intern Med. 2016;176:1687-1692.
3. Durante C, Costante G, Lucisano G, et al. The natural history of benign thyroid nodules. JAMA. 2015;313:926-935.
4. Choosing Wisely. Society of Hospital Medicine—Pediatric hospital medicine. Don’t use continuous pulse oximetry routinely in children with acute respiratory illness unless they are on supplemental oxygen. www.choosingwisely.org/clinician-lists/society-hospital-medicine-pediatric-continuous-pulse-oximetry-in-children-with-acute-respiratory-illness/. Accessed September 28, 2020.
5. Schondelmeyer AC, Simmons JM, Statile AM, et al. Using quality improvement to reduce continuous pulse oximetry use in children with wheezing. Pediatrics. 2015;135:e1044-e1051.
6. Kravitz RL, Bell RA, Azari R, et al. Direct observation of requests for clinical services in office practice: what do patients want and do they get it? Arch Intern Med. 2003;163:1673-1681.
7. Kravitz RL, Bell RA, Franz CE, et al. Characterizing patient requests and physician responses in office practice. Health Serv Res. 2002;37:217-238.
8. Choosing Wisely. American Academy of Family Physicians. Don’t do imaging for low back pain within the first six weeks, unless red flags are present. www.choosingwisely.org/clinician-lists/american-academy-family-physicians-imaging-low-back-pain/. Accessed September 28, 2020.
9. Choosing Wisely. American Society of Anesthesiologists–Pain Medicine. Avoid imaging studies (MRI, CT or X-rays) for acute low back pain without specific indications. www.choosingwisely.org/clinician-lists/american-society-anesthesiologists-imaging-studies-for-acute-low-back-pain/. Accessed September 28, 2020.
10. Choosing Wisely. American College of Emergency Physicians. Avoid lumbar spine imaging in the emergency department for adults with non-traumatic back pain unless the patient has severe or progressive neurologic deficits or is suspected of having a serious underlying condition (such as vertebral infection, cauda equina syndrome, or cancer with bony metastasis). www.choosingwisely.org/clinician-lists/acep-lumbar-spine-imaging-in-the-ed/. Accessed September 28, 2020.
11. Choosing Wisely. American Academy of Family Physicians. Don’t require a pelvic exam or other physical exam to prescribe oral contraceptive medications. www.choosingwisely.org/clinician-lists/american-academy-family-physicians-pelvic-or-physical-exams-to-prescribe-oral-contraceptives/. Accessed September 28, 2020.
12. Over-the-counter access to hormonal contraception. ACOG Committee Opinion, Number 788. Obstet Gynecol. 2019;134:e96-e105. https://journals.lww.com/greenjournal/Fulltext/2019/10000/Over_the_Counter_Access_to_Hormonal_Contraception_.46.aspx. Accessed September 28, 2020.
13. Choosing Wisely. American Academy of Family Physicians. Don’t routinely recommend daily home glucose monitoring for patients who have Type 2 diabetes mellitus and are not using insulin. www.choosingwisely.org/clinician-lists/aafp-daily-home-glucose-monitoring-for-patients-with-type-2-diabetes. Accessed September 28, 2020.
14. Choosing Wisely. Society of General Internal Medicine. Don’t recommend daily home finger glucose testing in patients with Type 2 diabetes mellitus not using insulin. www.choosingwisely.org/clinician-lists/society-general-internal-medicine-daily-home-finger-glucose-testing-type-2-diabetes-mellitus/. Accessed September 28, 2020.
15. Malanda UL, Welschen LM, Riphagen II, et al. Self‐monitoring of blood glucose in patients with type 2 diabetes mellitus who are not using insulin. Cochrane Database Syst Rev. 2012(1):CD005060.
16. Peel E, Douglas M, Lawton J. Self monitoring of blood glucose in type 2 diabetes: longitudinal qualitative study of patients’ perspectives. BMJ. 2007;335:493.
17. Choosing Wisely. American Academy of Family Physicians. Don’t screen for genital herpes simplex virus infection (HSV) in asymptomatic adults, including pregnant women. www.choosingwisely.org/clinician-lists/aafp-genital-herpes-screening-in-asymptomatic-adults/. Accessed September 28, 2020.
18. Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Serologic screening for genital herpes infection: US Preventive Services Task Force recommendation statement. JAMA. 2016;316:2525-2530.
19. Choosing Wisely. American Academy of Family Physicians. Don’t screen for testicular cancer in asymptomatic adolescent and adult males. www.choosingwisely.org/clinician-lists/aafp-testicular-cancer-screening-in-asymptomatic-adolescent-and-adult-men/. Accessed September 28, 2020.
20. Lin K, Sharangpani R. Screening for testicular cancer: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2010;153:396-399.
21. Choosing Wisely. American Academy of Pediatrics. Cough and cold medicines should not be prescribed, recommended or used for respiratory illnesses in young children. www.choosingwisely.org/clinician-lists/american-academy-pediatrics-cough-and-cold-medicines-for-children-under-four/. Accessed September 28, 2020.
22. Schaefer MK, Shehab N, Cohen AL, et al. Adverse events from cough and cold medications in children. Pediatrics. 2008;121:783-787.
23. Carr BC. Efficacy, abuse, and toxicity of over-the-counter cough and cold medicines in the pediatric population. Curr Opin Pediatr. 2006;18:184-188.
24. Oduwole O, Udoh EE, Oyo‐Ita A, et al. Honey for acute cough in children. Cochrane Database Syst Rev. 2018(4):CD007094.
25. Choosing Wisely. American Academy of Allergy, Asthma & Immunology. Don’t perform unproven diagnostic tests, such as immunoglobulin G(lgG) testing or an indiscriminate battery of immunoglobulin E(lgE) tests, in the evaluation of allergy. www.choosingwisely.org/clinician-lists/american-academy-allergy-asthma-immunology-diagnostic-tests-for-allergy-evaluation/. Accessed September 28, 2020.
26. Cox L, Williams B, Sicherer S, et al. Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology Specific IgE Test Task Force. Ann Allergy Asthma Immunol. 2008;101:580-592.
27. Choosing Wisely. American Epilepsy Society. Do not routinely order electroencephalogram (EEG) as part of initial syncope work-up. www.choosingwisely.org/clinician-lists/aes-eeg-as-part-of-initial-syncope-work-up/. Accessed September 28, 2020.
28. Choosing Wisely. American College of Emergency Physicians. Avoid CT of the head in asymptomatic adult patients in the emergency department with syncope, insignificant trauma and a normal neurological evaluation. www.choosingwisely.org/clinician-lists/acep-avoid-head-ct-for-asymptomatic-adults-with-syncope/. Accessed September 28, 2020.
29. Choosing Wisely. American College of Physicians. In the evaluation of simple syncope and a normal neurological examination, don’t obtain brain imaging studies (CT or MRI). www.choosingwisely.org/clinician-lists/american-college-physicians-brain-imaging-to-evaluate-simple-syncope/. Accessed September 28, 2020.
30. Choosing Wisely. American Academy of Neurology. Don’t perform imaging of the carotid arteries for simple syncope without other neurologic symptoms. www.choosingwisely.org/clinician-lists/american-academy-neurology-carotid-artery-imaging-for-simple-syncope/. Accessed September 28, 2020.
31. Josephson CB, Rahey S, Sadler RM. Neurocardiogenic syncope: frequency and consequences of its misdiagnosis as epilepsy. Can J Neurol Sci. 2007;34:221-224.
32. Mendu ML, McAvay G, Lampert R, et al. Yield of diagnostic tests in evaluating syncopal episodes in older patients. Arch Intern Med. 2009;169:1299-1305.
33. Choosing Wisely. American Academy of Pediatrics–Section on Surgery. Avoid referring most children with umbilical hernias to a pediatric surgeon until around age 4-5 years. www.choosingwisely.org/clinician-lists/aap-sosu-avoid-surgery-referral-for-umbilical-hernias-until-age-4-5/. Accessed September 28, 2020.
34. Antonoff MB, Kreykes NS, Saltzman DA, et al. American Academy of Pediatrics Section on Surgery hernia survey revisited. J Pediatr Surg. 2005;40:1009-1014.
35. Choosing Wisely. American Geriatrics Society. Avoid using prescription appetite stimulants or high-calorie supplements for treatment of anorexia or cachexia in older adults; instead, optimize social supports, discontinue medications that may interfere with eating, provide appealing food and feeding assistance, and clarify patient goals and expectations. www.choosingwisely.org/clinician-lists/american-geriatrics-society-prescription-appetite-stimulants-to-treat-anorexia-cachexia-in-elderly/. Accessed September 28, 2020.
36. Milne AC, Potter J, Vivanti A, et al. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Sys Rev. 2009(2):CD003288.
37. Fox CB, Treadway AK, Blaszczyk AT, et al. Megestrol acetate and mirtazapine for the treatment of unplanned weight loss in the elderly. Pharmacotherapy. 2009;29:383-397.
