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A week of anticoagulation halves post-PCI radial occlusion rate
Serious bleeding is not increased
BOSTON – Following transradial access for angiography or a percutaneous coronary intervention (PCI), a low dose of the factor Xa inhibitor rivaroxaban for 7 days reduces the risk of an access-site occlusion by 50%, according to results of the randomized RIVARAD trial.
Of two multicenter, randomized trials to address this question it is the larger, according to Rania Hammami, MD, who presented the results at the Transcatheter Cardiovascular Therapeutics annual meeting.
In the open-label RIVARAD trial, 538 patients were randomized to 10 mg rivaroxaban or standard care alone. Standard care at the beginning of the procedure included unfractionated heparin in a dose of 50 IU/kg for angiography and up to 100 IU/kg for PCI. Manual compression was applied at the end of the procedure followed by an evaluation for complications, such as hematoma or aneurysm.
For the primary outcome of radial access occlusion at 30 days, the lower rate in the rivaroxaban arm (6.9% vs. 13.0%) translated into a statistically significant 50% reduction (odds ratio, 0.50; P = .011).
Rivaroxaban preserves radial pulse
Rivaroxaban was also favored for the endpoint of inability at 30 days to find a radial pulse (5.8% vs. 12.2%; P = .01). Interestingly, there was some disparity for this endpoint for clinical examination and ultrasound.
“In 12 patients, we were able to palpate a radial pulse, but the ultrasound showed an occlusion of the vessel, while in 7 patients we could not find a radial pulse even though the radial artery was patent on ultrasound,” Dr. Hammami, of the department of cardiology, Hedi Chaker Hospital, Sfax, Tunisia, said at the meeting, sponsored by the Cardiovascular Research Foundation.
The incidence of hemorrhagic complications was higher in the rivaroxaban group (2.7% vs. 1.9%), but the difference did not approach statistical significance (OR, 1.5; P = .54). Moreover, all of the bleeding complications were minor (Bleeding Academic Research Consortium level 1), and none of the bleeding complications were observed in patients receiving rivaroxaban alone. Rather, all patients with bleeding were taking one or more antiplatelet drugs along with rivaroxaban.
On univariate analysis, several baseline characteristics were associated with subsequent radial occlusion, including female sex (P = .02), current smoking (P = .03), renal failure (P = .004), and PCI for acute coronary syndrome (P = .02). On multivariate analysis, female sex (P = .001) and current smoking (P < .0001) became even stronger predictors of occlusion on a statistical basis, while a prior procedure involving radial access was also a significant predictor (P = .029).
“One woman out of two developed radial access occlusion if she had a history of smoking and had a history of a transradial puncture,” Dr. Hammami reported.
In a subgroup analysis, relative protection from radial artery occlusion from a 7-day course of rivaroxaban was particularly pronounced in those with diabetes, renal failure, or hypertension relative to those without these conditions, but the protective effect appeared to be about the same regardless of body mass index, age, sheath size, or current use of statins.
These findings are consistent with other studies evaluating the risk of radial access occlusion, according to Dr. Hammami. While different studies she cited reported incidences ranging from less than 1% to more than 30%, the risk has typically been highest in populations with increased susceptibility for thrombus formation, such as smokers and patients with diabetes.
Preventing radial artery occlusion has several benefits, not least of which is preserving this access point for future interventions, according to Dr. Hammami.
RIVARAD is the largest study to evaluate an anticoagulant for the prevention of radial artery occlusion, but it is not the first. Earlier in 2022, a Chinese trial called RESTORE was published in Circulation: Cardiovascular Interventions. In that placebo-controlled study of 382 patients, 7 days of 10 mg rivaroxaban was also linked to a significant reduction in radial artery occlusion at 30 days (3.8% vs. 11.5%; P = .011).
“We don’t know if a higher dose of rivaroxaban would be more effective and equally safe,” said Dr. Hammami, but added that a Canadian trial called CAPITAL RAPTOR will test this premise. In this trial, there is a planned enrollment of 1,800 patients who will be randomized to 15 mg rivaroxaban or standard treatment.
Occlusion risk appears underappreciated
The risk of radial artery occlusion might be underappreciated. According to data cited by Dr. Hammami, only about half of interventionalists in the United States and fewer than 10% outside of the United States routinely assess radial artery patency in conjunction with radial-access PCI. The data from this trial suggest that the risk can be substantially reduced, particularly in high-risk patients, with anticoagulant therapy.
Agreeing that this is a potentially avoidable complication, Roxanna Mehran, MD, director of interventional cardiovascular research and clinical trials, Icahn School of Medicine at Mount Sinai, New York, called the RIVARAD study “a clinically meaningful trial,” and valuable for identifying risk factors as well as for showing a treatment effect and acceptable safety from a short course of a factor Xa inhibitor.
“This is very important work,” said Dr. Mehran, who praised the quality of the study and the contribution it makes for considering how and when prophylaxis is needed.
Dr. Hammami reported no potential conflicts of interest. Dr. Mehran has financial relationships with more than 25 pharmaceutical companies but none with the sponsor of this trial, which was funded by Philadelphia Pharma, a drug company based in Tunisia.
Serious bleeding is not increased
Serious bleeding is not increased
BOSTON – Following transradial access for angiography or a percutaneous coronary intervention (PCI), a low dose of the factor Xa inhibitor rivaroxaban for 7 days reduces the risk of an access-site occlusion by 50%, according to results of the randomized RIVARAD trial.
Of two multicenter, randomized trials to address this question it is the larger, according to Rania Hammami, MD, who presented the results at the Transcatheter Cardiovascular Therapeutics annual meeting.
In the open-label RIVARAD trial, 538 patients were randomized to 10 mg rivaroxaban or standard care alone. Standard care at the beginning of the procedure included unfractionated heparin in a dose of 50 IU/kg for angiography and up to 100 IU/kg for PCI. Manual compression was applied at the end of the procedure followed by an evaluation for complications, such as hematoma or aneurysm.
For the primary outcome of radial access occlusion at 30 days, the lower rate in the rivaroxaban arm (6.9% vs. 13.0%) translated into a statistically significant 50% reduction (odds ratio, 0.50; P = .011).
Rivaroxaban preserves radial pulse
Rivaroxaban was also favored for the endpoint of inability at 30 days to find a radial pulse (5.8% vs. 12.2%; P = .01). Interestingly, there was some disparity for this endpoint for clinical examination and ultrasound.
“In 12 patients, we were able to palpate a radial pulse, but the ultrasound showed an occlusion of the vessel, while in 7 patients we could not find a radial pulse even though the radial artery was patent on ultrasound,” Dr. Hammami, of the department of cardiology, Hedi Chaker Hospital, Sfax, Tunisia, said at the meeting, sponsored by the Cardiovascular Research Foundation.
The incidence of hemorrhagic complications was higher in the rivaroxaban group (2.7% vs. 1.9%), but the difference did not approach statistical significance (OR, 1.5; P = .54). Moreover, all of the bleeding complications were minor (Bleeding Academic Research Consortium level 1), and none of the bleeding complications were observed in patients receiving rivaroxaban alone. Rather, all patients with bleeding were taking one or more antiplatelet drugs along with rivaroxaban.
On univariate analysis, several baseline characteristics were associated with subsequent radial occlusion, including female sex (P = .02), current smoking (P = .03), renal failure (P = .004), and PCI for acute coronary syndrome (P = .02). On multivariate analysis, female sex (P = .001) and current smoking (P < .0001) became even stronger predictors of occlusion on a statistical basis, while a prior procedure involving radial access was also a significant predictor (P = .029).
“One woman out of two developed radial access occlusion if she had a history of smoking and had a history of a transradial puncture,” Dr. Hammami reported.
In a subgroup analysis, relative protection from radial artery occlusion from a 7-day course of rivaroxaban was particularly pronounced in those with diabetes, renal failure, or hypertension relative to those without these conditions, but the protective effect appeared to be about the same regardless of body mass index, age, sheath size, or current use of statins.
These findings are consistent with other studies evaluating the risk of radial access occlusion, according to Dr. Hammami. While different studies she cited reported incidences ranging from less than 1% to more than 30%, the risk has typically been highest in populations with increased susceptibility for thrombus formation, such as smokers and patients with diabetes.
Preventing radial artery occlusion has several benefits, not least of which is preserving this access point for future interventions, according to Dr. Hammami.
RIVARAD is the largest study to evaluate an anticoagulant for the prevention of radial artery occlusion, but it is not the first. Earlier in 2022, a Chinese trial called RESTORE was published in Circulation: Cardiovascular Interventions. In that placebo-controlled study of 382 patients, 7 days of 10 mg rivaroxaban was also linked to a significant reduction in radial artery occlusion at 30 days (3.8% vs. 11.5%; P = .011).
“We don’t know if a higher dose of rivaroxaban would be more effective and equally safe,” said Dr. Hammami, but added that a Canadian trial called CAPITAL RAPTOR will test this premise. In this trial, there is a planned enrollment of 1,800 patients who will be randomized to 15 mg rivaroxaban or standard treatment.
Occlusion risk appears underappreciated
The risk of radial artery occlusion might be underappreciated. According to data cited by Dr. Hammami, only about half of interventionalists in the United States and fewer than 10% outside of the United States routinely assess radial artery patency in conjunction with radial-access PCI. The data from this trial suggest that the risk can be substantially reduced, particularly in high-risk patients, with anticoagulant therapy.
Agreeing that this is a potentially avoidable complication, Roxanna Mehran, MD, director of interventional cardiovascular research and clinical trials, Icahn School of Medicine at Mount Sinai, New York, called the RIVARAD study “a clinically meaningful trial,” and valuable for identifying risk factors as well as for showing a treatment effect and acceptable safety from a short course of a factor Xa inhibitor.
“This is very important work,” said Dr. Mehran, who praised the quality of the study and the contribution it makes for considering how and when prophylaxis is needed.
Dr. Hammami reported no potential conflicts of interest. Dr. Mehran has financial relationships with more than 25 pharmaceutical companies but none with the sponsor of this trial, which was funded by Philadelphia Pharma, a drug company based in Tunisia.
BOSTON – Following transradial access for angiography or a percutaneous coronary intervention (PCI), a low dose of the factor Xa inhibitor rivaroxaban for 7 days reduces the risk of an access-site occlusion by 50%, according to results of the randomized RIVARAD trial.
Of two multicenter, randomized trials to address this question it is the larger, according to Rania Hammami, MD, who presented the results at the Transcatheter Cardiovascular Therapeutics annual meeting.
In the open-label RIVARAD trial, 538 patients were randomized to 10 mg rivaroxaban or standard care alone. Standard care at the beginning of the procedure included unfractionated heparin in a dose of 50 IU/kg for angiography and up to 100 IU/kg for PCI. Manual compression was applied at the end of the procedure followed by an evaluation for complications, such as hematoma or aneurysm.
For the primary outcome of radial access occlusion at 30 days, the lower rate in the rivaroxaban arm (6.9% vs. 13.0%) translated into a statistically significant 50% reduction (odds ratio, 0.50; P = .011).
Rivaroxaban preserves radial pulse
Rivaroxaban was also favored for the endpoint of inability at 30 days to find a radial pulse (5.8% vs. 12.2%; P = .01). Interestingly, there was some disparity for this endpoint for clinical examination and ultrasound.
“In 12 patients, we were able to palpate a radial pulse, but the ultrasound showed an occlusion of the vessel, while in 7 patients we could not find a radial pulse even though the radial artery was patent on ultrasound,” Dr. Hammami, of the department of cardiology, Hedi Chaker Hospital, Sfax, Tunisia, said at the meeting, sponsored by the Cardiovascular Research Foundation.
The incidence of hemorrhagic complications was higher in the rivaroxaban group (2.7% vs. 1.9%), but the difference did not approach statistical significance (OR, 1.5; P = .54). Moreover, all of the bleeding complications were minor (Bleeding Academic Research Consortium level 1), and none of the bleeding complications were observed in patients receiving rivaroxaban alone. Rather, all patients with bleeding were taking one or more antiplatelet drugs along with rivaroxaban.
On univariate analysis, several baseline characteristics were associated with subsequent radial occlusion, including female sex (P = .02), current smoking (P = .03), renal failure (P = .004), and PCI for acute coronary syndrome (P = .02). On multivariate analysis, female sex (P = .001) and current smoking (P < .0001) became even stronger predictors of occlusion on a statistical basis, while a prior procedure involving radial access was also a significant predictor (P = .029).
“One woman out of two developed radial access occlusion if she had a history of smoking and had a history of a transradial puncture,” Dr. Hammami reported.
In a subgroup analysis, relative protection from radial artery occlusion from a 7-day course of rivaroxaban was particularly pronounced in those with diabetes, renal failure, or hypertension relative to those without these conditions, but the protective effect appeared to be about the same regardless of body mass index, age, sheath size, or current use of statins.
These findings are consistent with other studies evaluating the risk of radial access occlusion, according to Dr. Hammami. While different studies she cited reported incidences ranging from less than 1% to more than 30%, the risk has typically been highest in populations with increased susceptibility for thrombus formation, such as smokers and patients with diabetes.
Preventing radial artery occlusion has several benefits, not least of which is preserving this access point for future interventions, according to Dr. Hammami.
RIVARAD is the largest study to evaluate an anticoagulant for the prevention of radial artery occlusion, but it is not the first. Earlier in 2022, a Chinese trial called RESTORE was published in Circulation: Cardiovascular Interventions. In that placebo-controlled study of 382 patients, 7 days of 10 mg rivaroxaban was also linked to a significant reduction in radial artery occlusion at 30 days (3.8% vs. 11.5%; P = .011).
“We don’t know if a higher dose of rivaroxaban would be more effective and equally safe,” said Dr. Hammami, but added that a Canadian trial called CAPITAL RAPTOR will test this premise. In this trial, there is a planned enrollment of 1,800 patients who will be randomized to 15 mg rivaroxaban or standard treatment.
Occlusion risk appears underappreciated
The risk of radial artery occlusion might be underappreciated. According to data cited by Dr. Hammami, only about half of interventionalists in the United States and fewer than 10% outside of the United States routinely assess radial artery patency in conjunction with radial-access PCI. The data from this trial suggest that the risk can be substantially reduced, particularly in high-risk patients, with anticoagulant therapy.
Agreeing that this is a potentially avoidable complication, Roxanna Mehran, MD, director of interventional cardiovascular research and clinical trials, Icahn School of Medicine at Mount Sinai, New York, called the RIVARAD study “a clinically meaningful trial,” and valuable for identifying risk factors as well as for showing a treatment effect and acceptable safety from a short course of a factor Xa inhibitor.
“This is very important work,” said Dr. Mehran, who praised the quality of the study and the contribution it makes for considering how and when prophylaxis is needed.
Dr. Hammami reported no potential conflicts of interest. Dr. Mehran has financial relationships with more than 25 pharmaceutical companies but none with the sponsor of this trial, which was funded by Philadelphia Pharma, a drug company based in Tunisia.
AT TCT 2022
Is acetaminophen really safer than NSAIDs in heart disease?
New research calls into question the assumption that acetaminophen is safer than NSAIDs for patients with known cardiovascular disease (CVD) or CVD risk factors.
The analysis found a significant correlation between the use of acetaminophen and elevated systolic blood pressure.
While acetaminophen may still be safer than NSAIDs from a bleeding risk standpoint, or in patients with known kidney disease, “the gap may not be as large as once thought,” Rahul Gupta, MD, cardiologist with Lehigh Valley Health Network, Allentown, Pa., said in an interview.
“Cautious use is recommended over the long term, especially in patients with pre-existing hypertension or cardiovascular risk factors,” Dr. Gupta said.
The study was presented at the Hypertension Scientific Sessions, San Diego, sponsored by the American Heart Association.
Acetaminophen is one of the most widely used over-the-counter medications, as it is considered a safer medication for long-term use since it lacks the anti-inflammatory effects of NSAIDs, Dr. Gupta explained.
NSAIDs have been known to raise blood pressure, but the effect of acetaminophen in this regard has not been well studied. Observational studies have shown contradictory results in terms of its effect on blood pressure, he noted.
To investigate further, Dr. Gupta and colleagues did a meta-analysis of three studies that compared the effect of acetaminophen (3-4 g/day) versus placebo on systolic and diastolic ambulatory blood pressure in patients with heart disease or hypertension. Together, the studies included 172 adults (mean age, 60 years; 73% male).
They found that patients receiving acetaminophen had significantly higher systolic blood pressure, compared with those receiving placebo (standard mean difference [SMD] = 0.35; 95% confidence interval, 0.08-0.63; P = .01).
Subgroup analysis of the effect on hypertensive patients showed significant change in systolic blood pressure as well (SMD = 0.38; 95% CI, 0.05-0.71; P = .02).
“Interestingly, there was no significant difference in the effect on diastolic blood pressure,” Dr. Gupta commented.
Reached for comment, Timothy S. Anderson, MD, clinical investigator in the Division of General Medicine at Beth Israel Deaconess Medical Center and assistant professor of medicine at the Harvard Medical School, both in Boston, said this is “an interesting and not particularly well-known issue.”
“However, most of the trials look at very high doses of acetaminophen use (for example, six to eight of the 500 mg pills each day) so we don’t really know whether the more common patterns of using one to two acetaminophen pills every once in a while is problematic,” Dr. Anderson told this news organization.
“We also don’t have data showing a direct harm from these medications with regards to strokes or heart attacks or other downstream consequences of high blood pressure. Ideally we would need a head-to-head trial comparing ibuprofen-type medications to acetaminophen-type medications,” Dr. Anderson said.
The study had no specific funding. Dr. Gupta and Dr. Anderson reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
New research calls into question the assumption that acetaminophen is safer than NSAIDs for patients with known cardiovascular disease (CVD) or CVD risk factors.
The analysis found a significant correlation between the use of acetaminophen and elevated systolic blood pressure.
While acetaminophen may still be safer than NSAIDs from a bleeding risk standpoint, or in patients with known kidney disease, “the gap may not be as large as once thought,” Rahul Gupta, MD, cardiologist with Lehigh Valley Health Network, Allentown, Pa., said in an interview.
“Cautious use is recommended over the long term, especially in patients with pre-existing hypertension or cardiovascular risk factors,” Dr. Gupta said.
The study was presented at the Hypertension Scientific Sessions, San Diego, sponsored by the American Heart Association.
Acetaminophen is one of the most widely used over-the-counter medications, as it is considered a safer medication for long-term use since it lacks the anti-inflammatory effects of NSAIDs, Dr. Gupta explained.
NSAIDs have been known to raise blood pressure, but the effect of acetaminophen in this regard has not been well studied. Observational studies have shown contradictory results in terms of its effect on blood pressure, he noted.
To investigate further, Dr. Gupta and colleagues did a meta-analysis of three studies that compared the effect of acetaminophen (3-4 g/day) versus placebo on systolic and diastolic ambulatory blood pressure in patients with heart disease or hypertension. Together, the studies included 172 adults (mean age, 60 years; 73% male).
They found that patients receiving acetaminophen had significantly higher systolic blood pressure, compared with those receiving placebo (standard mean difference [SMD] = 0.35; 95% confidence interval, 0.08-0.63; P = .01).
Subgroup analysis of the effect on hypertensive patients showed significant change in systolic blood pressure as well (SMD = 0.38; 95% CI, 0.05-0.71; P = .02).
“Interestingly, there was no significant difference in the effect on diastolic blood pressure,” Dr. Gupta commented.
Reached for comment, Timothy S. Anderson, MD, clinical investigator in the Division of General Medicine at Beth Israel Deaconess Medical Center and assistant professor of medicine at the Harvard Medical School, both in Boston, said this is “an interesting and not particularly well-known issue.”
“However, most of the trials look at very high doses of acetaminophen use (for example, six to eight of the 500 mg pills each day) so we don’t really know whether the more common patterns of using one to two acetaminophen pills every once in a while is problematic,” Dr. Anderson told this news organization.
“We also don’t have data showing a direct harm from these medications with regards to strokes or heart attacks or other downstream consequences of high blood pressure. Ideally we would need a head-to-head trial comparing ibuprofen-type medications to acetaminophen-type medications,” Dr. Anderson said.
The study had no specific funding. Dr. Gupta and Dr. Anderson reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
New research calls into question the assumption that acetaminophen is safer than NSAIDs for patients with known cardiovascular disease (CVD) or CVD risk factors.
The analysis found a significant correlation between the use of acetaminophen and elevated systolic blood pressure.
While acetaminophen may still be safer than NSAIDs from a bleeding risk standpoint, or in patients with known kidney disease, “the gap may not be as large as once thought,” Rahul Gupta, MD, cardiologist with Lehigh Valley Health Network, Allentown, Pa., said in an interview.
“Cautious use is recommended over the long term, especially in patients with pre-existing hypertension or cardiovascular risk factors,” Dr. Gupta said.
The study was presented at the Hypertension Scientific Sessions, San Diego, sponsored by the American Heart Association.
Acetaminophen is one of the most widely used over-the-counter medications, as it is considered a safer medication for long-term use since it lacks the anti-inflammatory effects of NSAIDs, Dr. Gupta explained.
NSAIDs have been known to raise blood pressure, but the effect of acetaminophen in this regard has not been well studied. Observational studies have shown contradictory results in terms of its effect on blood pressure, he noted.
To investigate further, Dr. Gupta and colleagues did a meta-analysis of three studies that compared the effect of acetaminophen (3-4 g/day) versus placebo on systolic and diastolic ambulatory blood pressure in patients with heart disease or hypertension. Together, the studies included 172 adults (mean age, 60 years; 73% male).
They found that patients receiving acetaminophen had significantly higher systolic blood pressure, compared with those receiving placebo (standard mean difference [SMD] = 0.35; 95% confidence interval, 0.08-0.63; P = .01).
Subgroup analysis of the effect on hypertensive patients showed significant change in systolic blood pressure as well (SMD = 0.38; 95% CI, 0.05-0.71; P = .02).
“Interestingly, there was no significant difference in the effect on diastolic blood pressure,” Dr. Gupta commented.
Reached for comment, Timothy S. Anderson, MD, clinical investigator in the Division of General Medicine at Beth Israel Deaconess Medical Center and assistant professor of medicine at the Harvard Medical School, both in Boston, said this is “an interesting and not particularly well-known issue.”
“However, most of the trials look at very high doses of acetaminophen use (for example, six to eight of the 500 mg pills each day) so we don’t really know whether the more common patterns of using one to two acetaminophen pills every once in a while is problematic,” Dr. Anderson told this news organization.
“We also don’t have data showing a direct harm from these medications with regards to strokes or heart attacks or other downstream consequences of high blood pressure. Ideally we would need a head-to-head trial comparing ibuprofen-type medications to acetaminophen-type medications,” Dr. Anderson said.
The study had no specific funding. Dr. Gupta and Dr. Anderson reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM HYPERTENSION 2022
TAVR now used in almost 50% of younger severe aortic stenosis patients
Among patients with severe isolated aortic stenosis younger than 65, the rate of transcatheter aortic valve replacement (TAVR) now almost matches that of surgical aortic valve replacement (SAVR), despite guideline recommendations to the contrary, a study in a national U.S. population shows.
The 2020 American Heart Association/American College of Cardiology (AHA/ACC) valve guideline recommends SAVR for patients younger than 65 with severe aortic stenosis, the researchers note, but their study showed “near equal utilization between TAVR and SAVR in these younger patients by 2021,” at 48% and 52% respectively.
Toishi Sharma, MD, and colleagues presented these findings in an oral poster session at Transcatheter Cardiovascular Therapeutics 2022, and the study was simultaneously published as a Research Letter in the Journal of the American College of Cardiology (JACC).
“To our knowledge, the current findings represent the first national temporal trends study stratifying [aortic stenosis] therapies according to guideline-recommended age groups: our observations demonstrate the dramatic growth of TAVR in all age groups, including young patients,” the researchers conclude.
They analyzed changes in rates of TAVR and SAVR in a U.S. sample stratified by age: younger than 65 years, 65-80, and older than 80 years.
These findings have implications for lifetime management of younger patients who undergo TAVR, they write, “including issues related to lifetime coronary access, valve durability, and the potential for subsequent TAVR procedures over time.”
Three age groups
In a study published in JACC, this group examined changes in uptake of TAVR versus SAVR in 4,161 patients with aortic stenosis in Vermont, New Hampshire, and Maine, senior author Harold L. Dauerman, MD, said in an interview.
The greatest rate of rise of TAVR was in the group younger than 65, but that study ended in 2019, said Dr. Dauerman, from the University of Vermont Health Network, Burlington.
The 2020 guideline stratifies TAVR and SAVR recommendations such that “less than 65 should primarily be a surgical approach and greater than 80 primarily a TAVR approach, while 65 to 80 is a gray zone, and shared decision-making becomes important,” he noted.
The group hypothesized that recent trials and technology have led to a national increase in TAVR in people younger than 65.
From the Vizient clinical database, including more than 250 U.S. academic centers that perform both TAVR and SAVR, the researchers identified 142,953 patients who underwent TAVR or SAVR for isolated aortic stenosis from Oct. 1, 2015, to Dec. 31, 2021. From 2015 to 2021, the valve replacement rates in the three age groups changed as follows:
- Age less than 65: TAVR rose from 17% to 48%; SAVR fell from 83% to 52%.
- Age 65-80: TAVR rose from 46% to 87%; SAVR fell from 54% to 12%.
- Age greater than 80: TAVR rose from 83% to 99%; SAVR fell from 16% to 1%.
“All ages have grown in the last 7 years in TAVR,” Dr. Dauerman summarized. “The one that’s surprising, and in contradiction to the guideline, is the growth of TAVR in young patients less than 65.”
Among patients younger than 65, prior bypass surgery and congestive heart failure predicted the use of TAVR instead of surgery, whereas bicuspid aortic valve disease was the biggest predictor of surgery instead of TAVR.
Most studies on TAVR valve durability are limited to patients in the randomized trials who were primarily in their mid-70s to mid-80s, some of whom died before a 10-year follow-up, Dr. Dauerman noted.
European guidelines recommend surgery for patients younger than 70, and it would be interesting to see if clinicians there follow this recommendation or if TAVR is now the preferred approach, he added.
There is a need for further, longer study of TAVR in younger patients, he said, to determine whether there are long-term clinical issues of concern.
Strategy depends on more than age
The “findings are not too surprising,” John Carroll, MD, who was not involved in this research, said in an email.
“Age is only one of multiple patient characteristics that enter into consideration of TAVR versus SAVR,” said Dr. Carroll, from Anschutz Medical Campus, University of Colorado, Aurora.
“As the article reports,” he noted, “those less than 65 having TAVR are more likely to have comorbid conditions that likely made the risk of SAVR higher.”
Dr. Carroll was lead author of a review article published in 2020 based on data from the ACC–Society of Thoracic Surgeons (STS)–Transcatheter Valve Therapy (TVT) registry on 276,316 patients who had TAVR in the United States from 2011-2019.
He pointed out that Figure 2 in that review shows that “SAVR is often performed in conjunction with other surgical procedures – another major reason why SAVR remains an important treatment for valvular heart disease.”
“We are awaiting long-term data comparing TAVR to SAVR durability,” Dr. Carroll added, echoing Dr. Dauerman. “So far [there are] no major differences, but it remains a key need to fully understand TAVR and the various models in commercial use.”
“Both TAVR and SAVR used in adults are tissue valves (SAVR with mechanical valves is used in younger patients),” Dr. Carroll noted, “and all tissue valves will eventually fail if the patient lives long enough.”
Patient management strategies need to consider what treatment options exist when the first valve fails. “If the first valve is SAVR, there is now extensive experience with placing a TAVR valve inside a failing SAVR valve, so called Valve-in-Valve or TAVR-in-SAVR. This is the preferred treatment in most patients with failing SAVR valves,” he said.
“On the other hand,” he continued, “we are just beginning to see more and more patients with failing TAVR valves, and the TAVR-in-TAVR procedure is less well understood.”
“Issues such as acute coronary occlusion and long-term difficulty in accessing coronary arteries are being encountered in some patients having TAVR-in-TAVR,” Dr. Carroll noted, which he discusses in a recent editorial he coauthored about the complexities of redo TAVR, published in JACC: Cardiovascular Interventions.
The study received no funding. Dr. Dauerman has research grants and is a consultant for Medtronic and Boston Scientific. Dr. Carroll is a local principal investigator in trials sponsored by Medtronic, Abbott, and Edwards Lifesciences.
A version of this article first appeared on Medscape.com.
Among patients with severe isolated aortic stenosis younger than 65, the rate of transcatheter aortic valve replacement (TAVR) now almost matches that of surgical aortic valve replacement (SAVR), despite guideline recommendations to the contrary, a study in a national U.S. population shows.
The 2020 American Heart Association/American College of Cardiology (AHA/ACC) valve guideline recommends SAVR for patients younger than 65 with severe aortic stenosis, the researchers note, but their study showed “near equal utilization between TAVR and SAVR in these younger patients by 2021,” at 48% and 52% respectively.
Toishi Sharma, MD, and colleagues presented these findings in an oral poster session at Transcatheter Cardiovascular Therapeutics 2022, and the study was simultaneously published as a Research Letter in the Journal of the American College of Cardiology (JACC).
“To our knowledge, the current findings represent the first national temporal trends study stratifying [aortic stenosis] therapies according to guideline-recommended age groups: our observations demonstrate the dramatic growth of TAVR in all age groups, including young patients,” the researchers conclude.
They analyzed changes in rates of TAVR and SAVR in a U.S. sample stratified by age: younger than 65 years, 65-80, and older than 80 years.
These findings have implications for lifetime management of younger patients who undergo TAVR, they write, “including issues related to lifetime coronary access, valve durability, and the potential for subsequent TAVR procedures over time.”
Three age groups
In a study published in JACC, this group examined changes in uptake of TAVR versus SAVR in 4,161 patients with aortic stenosis in Vermont, New Hampshire, and Maine, senior author Harold L. Dauerman, MD, said in an interview.
The greatest rate of rise of TAVR was in the group younger than 65, but that study ended in 2019, said Dr. Dauerman, from the University of Vermont Health Network, Burlington.
The 2020 guideline stratifies TAVR and SAVR recommendations such that “less than 65 should primarily be a surgical approach and greater than 80 primarily a TAVR approach, while 65 to 80 is a gray zone, and shared decision-making becomes important,” he noted.
The group hypothesized that recent trials and technology have led to a national increase in TAVR in people younger than 65.
From the Vizient clinical database, including more than 250 U.S. academic centers that perform both TAVR and SAVR, the researchers identified 142,953 patients who underwent TAVR or SAVR for isolated aortic stenosis from Oct. 1, 2015, to Dec. 31, 2021. From 2015 to 2021, the valve replacement rates in the three age groups changed as follows:
- Age less than 65: TAVR rose from 17% to 48%; SAVR fell from 83% to 52%.
- Age 65-80: TAVR rose from 46% to 87%; SAVR fell from 54% to 12%.
- Age greater than 80: TAVR rose from 83% to 99%; SAVR fell from 16% to 1%.
“All ages have grown in the last 7 years in TAVR,” Dr. Dauerman summarized. “The one that’s surprising, and in contradiction to the guideline, is the growth of TAVR in young patients less than 65.”
Among patients younger than 65, prior bypass surgery and congestive heart failure predicted the use of TAVR instead of surgery, whereas bicuspid aortic valve disease was the biggest predictor of surgery instead of TAVR.
Most studies on TAVR valve durability are limited to patients in the randomized trials who were primarily in their mid-70s to mid-80s, some of whom died before a 10-year follow-up, Dr. Dauerman noted.
European guidelines recommend surgery for patients younger than 70, and it would be interesting to see if clinicians there follow this recommendation or if TAVR is now the preferred approach, he added.
There is a need for further, longer study of TAVR in younger patients, he said, to determine whether there are long-term clinical issues of concern.
Strategy depends on more than age
The “findings are not too surprising,” John Carroll, MD, who was not involved in this research, said in an email.
“Age is only one of multiple patient characteristics that enter into consideration of TAVR versus SAVR,” said Dr. Carroll, from Anschutz Medical Campus, University of Colorado, Aurora.
“As the article reports,” he noted, “those less than 65 having TAVR are more likely to have comorbid conditions that likely made the risk of SAVR higher.”
Dr. Carroll was lead author of a review article published in 2020 based on data from the ACC–Society of Thoracic Surgeons (STS)–Transcatheter Valve Therapy (TVT) registry on 276,316 patients who had TAVR in the United States from 2011-2019.
He pointed out that Figure 2 in that review shows that “SAVR is often performed in conjunction with other surgical procedures – another major reason why SAVR remains an important treatment for valvular heart disease.”
“We are awaiting long-term data comparing TAVR to SAVR durability,” Dr. Carroll added, echoing Dr. Dauerman. “So far [there are] no major differences, but it remains a key need to fully understand TAVR and the various models in commercial use.”
“Both TAVR and SAVR used in adults are tissue valves (SAVR with mechanical valves is used in younger patients),” Dr. Carroll noted, “and all tissue valves will eventually fail if the patient lives long enough.”
Patient management strategies need to consider what treatment options exist when the first valve fails. “If the first valve is SAVR, there is now extensive experience with placing a TAVR valve inside a failing SAVR valve, so called Valve-in-Valve or TAVR-in-SAVR. This is the preferred treatment in most patients with failing SAVR valves,” he said.
“On the other hand,” he continued, “we are just beginning to see more and more patients with failing TAVR valves, and the TAVR-in-TAVR procedure is less well understood.”
“Issues such as acute coronary occlusion and long-term difficulty in accessing coronary arteries are being encountered in some patients having TAVR-in-TAVR,” Dr. Carroll noted, which he discusses in a recent editorial he coauthored about the complexities of redo TAVR, published in JACC: Cardiovascular Interventions.
The study received no funding. Dr. Dauerman has research grants and is a consultant for Medtronic and Boston Scientific. Dr. Carroll is a local principal investigator in trials sponsored by Medtronic, Abbott, and Edwards Lifesciences.
A version of this article first appeared on Medscape.com.
Among patients with severe isolated aortic stenosis younger than 65, the rate of transcatheter aortic valve replacement (TAVR) now almost matches that of surgical aortic valve replacement (SAVR), despite guideline recommendations to the contrary, a study in a national U.S. population shows.
The 2020 American Heart Association/American College of Cardiology (AHA/ACC) valve guideline recommends SAVR for patients younger than 65 with severe aortic stenosis, the researchers note, but their study showed “near equal utilization between TAVR and SAVR in these younger patients by 2021,” at 48% and 52% respectively.
Toishi Sharma, MD, and colleagues presented these findings in an oral poster session at Transcatheter Cardiovascular Therapeutics 2022, and the study was simultaneously published as a Research Letter in the Journal of the American College of Cardiology (JACC).
“To our knowledge, the current findings represent the first national temporal trends study stratifying [aortic stenosis] therapies according to guideline-recommended age groups: our observations demonstrate the dramatic growth of TAVR in all age groups, including young patients,” the researchers conclude.
They analyzed changes in rates of TAVR and SAVR in a U.S. sample stratified by age: younger than 65 years, 65-80, and older than 80 years.
These findings have implications for lifetime management of younger patients who undergo TAVR, they write, “including issues related to lifetime coronary access, valve durability, and the potential for subsequent TAVR procedures over time.”
Three age groups
In a study published in JACC, this group examined changes in uptake of TAVR versus SAVR in 4,161 patients with aortic stenosis in Vermont, New Hampshire, and Maine, senior author Harold L. Dauerman, MD, said in an interview.
The greatest rate of rise of TAVR was in the group younger than 65, but that study ended in 2019, said Dr. Dauerman, from the University of Vermont Health Network, Burlington.
The 2020 guideline stratifies TAVR and SAVR recommendations such that “less than 65 should primarily be a surgical approach and greater than 80 primarily a TAVR approach, while 65 to 80 is a gray zone, and shared decision-making becomes important,” he noted.
The group hypothesized that recent trials and technology have led to a national increase in TAVR in people younger than 65.
From the Vizient clinical database, including more than 250 U.S. academic centers that perform both TAVR and SAVR, the researchers identified 142,953 patients who underwent TAVR or SAVR for isolated aortic stenosis from Oct. 1, 2015, to Dec. 31, 2021. From 2015 to 2021, the valve replacement rates in the three age groups changed as follows:
- Age less than 65: TAVR rose from 17% to 48%; SAVR fell from 83% to 52%.
- Age 65-80: TAVR rose from 46% to 87%; SAVR fell from 54% to 12%.
- Age greater than 80: TAVR rose from 83% to 99%; SAVR fell from 16% to 1%.
“All ages have grown in the last 7 years in TAVR,” Dr. Dauerman summarized. “The one that’s surprising, and in contradiction to the guideline, is the growth of TAVR in young patients less than 65.”
Among patients younger than 65, prior bypass surgery and congestive heart failure predicted the use of TAVR instead of surgery, whereas bicuspid aortic valve disease was the biggest predictor of surgery instead of TAVR.
Most studies on TAVR valve durability are limited to patients in the randomized trials who were primarily in their mid-70s to mid-80s, some of whom died before a 10-year follow-up, Dr. Dauerman noted.
European guidelines recommend surgery for patients younger than 70, and it would be interesting to see if clinicians there follow this recommendation or if TAVR is now the preferred approach, he added.
There is a need for further, longer study of TAVR in younger patients, he said, to determine whether there are long-term clinical issues of concern.
Strategy depends on more than age
The “findings are not too surprising,” John Carroll, MD, who was not involved in this research, said in an email.
“Age is only one of multiple patient characteristics that enter into consideration of TAVR versus SAVR,” said Dr. Carroll, from Anschutz Medical Campus, University of Colorado, Aurora.
“As the article reports,” he noted, “those less than 65 having TAVR are more likely to have comorbid conditions that likely made the risk of SAVR higher.”
Dr. Carroll was lead author of a review article published in 2020 based on data from the ACC–Society of Thoracic Surgeons (STS)–Transcatheter Valve Therapy (TVT) registry on 276,316 patients who had TAVR in the United States from 2011-2019.
He pointed out that Figure 2 in that review shows that “SAVR is often performed in conjunction with other surgical procedures – another major reason why SAVR remains an important treatment for valvular heart disease.”
“We are awaiting long-term data comparing TAVR to SAVR durability,” Dr. Carroll added, echoing Dr. Dauerman. “So far [there are] no major differences, but it remains a key need to fully understand TAVR and the various models in commercial use.”
“Both TAVR and SAVR used in adults are tissue valves (SAVR with mechanical valves is used in younger patients),” Dr. Carroll noted, “and all tissue valves will eventually fail if the patient lives long enough.”
Patient management strategies need to consider what treatment options exist when the first valve fails. “If the first valve is SAVR, there is now extensive experience with placing a TAVR valve inside a failing SAVR valve, so called Valve-in-Valve or TAVR-in-SAVR. This is the preferred treatment in most patients with failing SAVR valves,” he said.
“On the other hand,” he continued, “we are just beginning to see more and more patients with failing TAVR valves, and the TAVR-in-TAVR procedure is less well understood.”
“Issues such as acute coronary occlusion and long-term difficulty in accessing coronary arteries are being encountered in some patients having TAVR-in-TAVR,” Dr. Carroll noted, which he discusses in a recent editorial he coauthored about the complexities of redo TAVR, published in JACC: Cardiovascular Interventions.
The study received no funding. Dr. Dauerman has research grants and is a consultant for Medtronic and Boston Scientific. Dr. Carroll is a local principal investigator in trials sponsored by Medtronic, Abbott, and Edwards Lifesciences.
A version of this article first appeared on Medscape.com.
FROM TCT 2022
In cardiogenic shock, edge-to-edge mitral valve repair improves outcome
In patients with severe mitral regurgitation (MR) and cardiogenic shock, successful transcatheter edge-to-edge repair (TEER) is associated with a substantial reduction in all-cause mortality and lower morbidity at 1 year, according to an analysis of registry data.
The data from this analysis also confirm that “successful reduction of MR is achievable with TEER in most patients with cardiogenic shock,” reported Mohamad A. Alkhouli, MD, an interventional cardiologist and professor of medicine at the Mayo Clinic, Rochester, Minn.
In those with device success, achieved in 85.6% of patients, all-cause mortality was about 21% lower (34.6% vs. 55.5%; P < .001) at 1 year than in those who were not successfully repaired, according to Dr. Alkhouli, who presented the findings at the Transcatheter Cardiovascular Therapeutics annual meeting in Boston. This translated into a reduction in the hazard ratio for death of nearly 50% (hazard ratio, 0.52; 95% confidence interval, 0.43-0.63).
A similar relative benefit was found for the composite endpoint of mortality and heart failure admissions at 1 year. Whether unadjusted (HR, 0.54; 95% CI, 0.45-0.66) or adjusted (HR, 0.51; 95% CI, 0.42-0.62), risk reductions with successful MR reduction, defined as greater than or equal to 1 grade improvement and a final MR grade of less than or equal to 2+, indicated that major adverse outcomes are reduced by about half.
STS/ACC TCT registry data queried
Drawn from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, 3,797 patients with cardiogenic shock underwent MR repair between November 2013 and December 2021. Outcomes at 1 year were evaluable in 2,773 of these patients. For inclusion, all had to meet at least one of the definitions of cardiogenic shock, such as inotrope use or mechanical circulatory support.
At baseline, 94.5% had a MR severity of at least 3+, and most of these had 4+. Thirty days after treatment, 88.8% had MR severity of 2+ or less, the majority of which had a severity of 1+.
These data address an important question not previously well studied, according to Dr. Alkhouli. In MR patients, cardiogenic shock is associated with a high risk of death, but there has been little evidence that valve repair does not exacerbate, let alone modify, this risk.
These data support the value of intervention, which was performed in almost all patients with MitraClipä (Abbott), the only device available for most of the period in which the registry was queried. However, Dr. Alkhouli cautioned that his data are best considered “hypothesis generating.”
“We need a randomized trial,” he said at the meeting sponsored by the Cardiovascular Research Foundation. He pointed out that this is a complex population for which multiple variables might have skewed results when data are analyzed retrospectively. Not least, those MR patients with cardiogenic shock in the database considered for TEER might well have been relatively healthy and not representative of an unselected population with both MR and cardiogenic shock.
The question might be better answered by the multicenter Canadian trial CAPITAL MINOS, which has just started. Described in an article in the American Heart Journal, it has a planned enrollment of about 150 MR patients with cardiogenic shock randomized to TEER or medical therapy. Results are expected in about 1 year, according to Dr. Alkhouli.
But regarding the present analysis, Dr. Alkhouli did note that sensitivity analyses conducted within his data across risk factors, such as degenerative versus nondegenerative MR, low (< 30%) versus higher left ventricular ejection fraction (LVEF), and presence or absence of an acute coronary syndrome (ACS), consistently supported a benefit from intervention.
Also, cardiogenic shock did not appear to be a factor in device failure, according to Dr. Alkhouli, addressing a potential criticism that cardiogenic shock was an underlying reason for device failure.
More than 90% in NYHA class III or IV heart failure
In this study, the mean age was 73 years. More than 90% were in class III or IV heart failure in the 2 weeks prior to TEER. More than half had established coronary artery disease. Other concomitant cardiovascular morbidities, including atrial fibrillation or flutter (65%), prior MI (39%), and prior stroke or transient ischemic attach (> 10%) were well represented.
When those with device success were compared with those with device failure, the risk profile was comparable. The predicted STS (Society of Thoracic Surgeons) mortality for mitral valve repair among these two groups was 14.8% versus 15% (P = 0.97), respectively.
However, those with device failure did have a lower baseline left ventricular ejection fraction (40.7% vs. 42.9%; P = .009) and a greater prevalence of moderate-to-severe or severe MR (96.1% vs. 84.9%; P < 0.001).
The growing experience with TEER means that benefit has now been shown in several complicated MR groups, such as those with severe ventricular dysfunction, renal insufficiency, and obstructive lung disease. This was a rationale for looking at the impact or repairing MR in patients with cardiogenic shock.
It is a pressing question, according to Dr. Alkhouli. He cited studies suggesting that up to 20% of patients hospitalized for cardiogenic shock have at least moderate-to-severe MR. Conversely, cardiogenic shock is not an uncommon finding in patients with MR.
While Dr. Alkhouli acknowledged that the many variables influencing outcome in patients with MR and cardiogenic shock will make a randomized trial “challenging,” many experts echoed this concern and even expressed some skepticism about the potential for an unbiased trial.
Data confirm MR repair is safe during shock
“These data do show that repair of MR is safe in patients safe in patients with cardiogenic shock,” said Anita W. Asgar, MD, an interventional cardiologist associated with the Montreal Heart Institute. She noted that there was a 5- to 6-day delay among the cardiogenic shock patients prior to undergoing MR repair in this analysis, potentially reflecting an elimination of those at very high risk. Similarly, she suggested that many interventionalists are likely to consider multiple variables before proceeding.
As a result, MR repair may not be amenable to randomization in a cardiogenic shock population, given that this decision is not typically undertaken out of the context of multiple variables.
“I am not sure that a clinical trial is ethical,” she said. She would expect that clinicians enrolling patients would only do so on a selective basis.
Alexandra J. Lansky, MD, Director of the Yale Heart and Vascular Research Program, Yale University, New Haven, Conn., also emphasized the difficulty of controlling for variables, such as the duration of cardiogenic shock, that influence decision-making.
Nevertheless, she called the data “very important” in that they at least lend some objective data for deciding whether to intervene a group of “challenging” patients not uncommonly faced in clinical practice.
Dr. Alkhouli reports financial relationships with Abbott Vascular, Boston Scientific, Johnson & Johnson, and Phillips. Dr. Asgar reports financial relationships with Abbott Vascular, Edwards Lifesciences, W.L. Gore & Associates, and Medtronic. Dr. Lasky reports no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
In patients with severe mitral regurgitation (MR) and cardiogenic shock, successful transcatheter edge-to-edge repair (TEER) is associated with a substantial reduction in all-cause mortality and lower morbidity at 1 year, according to an analysis of registry data.
The data from this analysis also confirm that “successful reduction of MR is achievable with TEER in most patients with cardiogenic shock,” reported Mohamad A. Alkhouli, MD, an interventional cardiologist and professor of medicine at the Mayo Clinic, Rochester, Minn.
In those with device success, achieved in 85.6% of patients, all-cause mortality was about 21% lower (34.6% vs. 55.5%; P < .001) at 1 year than in those who were not successfully repaired, according to Dr. Alkhouli, who presented the findings at the Transcatheter Cardiovascular Therapeutics annual meeting in Boston. This translated into a reduction in the hazard ratio for death of nearly 50% (hazard ratio, 0.52; 95% confidence interval, 0.43-0.63).
A similar relative benefit was found for the composite endpoint of mortality and heart failure admissions at 1 year. Whether unadjusted (HR, 0.54; 95% CI, 0.45-0.66) or adjusted (HR, 0.51; 95% CI, 0.42-0.62), risk reductions with successful MR reduction, defined as greater than or equal to 1 grade improvement and a final MR grade of less than or equal to 2+, indicated that major adverse outcomes are reduced by about half.
STS/ACC TCT registry data queried
Drawn from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, 3,797 patients with cardiogenic shock underwent MR repair between November 2013 and December 2021. Outcomes at 1 year were evaluable in 2,773 of these patients. For inclusion, all had to meet at least one of the definitions of cardiogenic shock, such as inotrope use or mechanical circulatory support.
At baseline, 94.5% had a MR severity of at least 3+, and most of these had 4+. Thirty days after treatment, 88.8% had MR severity of 2+ or less, the majority of which had a severity of 1+.
These data address an important question not previously well studied, according to Dr. Alkhouli. In MR patients, cardiogenic shock is associated with a high risk of death, but there has been little evidence that valve repair does not exacerbate, let alone modify, this risk.
These data support the value of intervention, which was performed in almost all patients with MitraClipä (Abbott), the only device available for most of the period in which the registry was queried. However, Dr. Alkhouli cautioned that his data are best considered “hypothesis generating.”
“We need a randomized trial,” he said at the meeting sponsored by the Cardiovascular Research Foundation. He pointed out that this is a complex population for which multiple variables might have skewed results when data are analyzed retrospectively. Not least, those MR patients with cardiogenic shock in the database considered for TEER might well have been relatively healthy and not representative of an unselected population with both MR and cardiogenic shock.
The question might be better answered by the multicenter Canadian trial CAPITAL MINOS, which has just started. Described in an article in the American Heart Journal, it has a planned enrollment of about 150 MR patients with cardiogenic shock randomized to TEER or medical therapy. Results are expected in about 1 year, according to Dr. Alkhouli.
But regarding the present analysis, Dr. Alkhouli did note that sensitivity analyses conducted within his data across risk factors, such as degenerative versus nondegenerative MR, low (< 30%) versus higher left ventricular ejection fraction (LVEF), and presence or absence of an acute coronary syndrome (ACS), consistently supported a benefit from intervention.
Also, cardiogenic shock did not appear to be a factor in device failure, according to Dr. Alkhouli, addressing a potential criticism that cardiogenic shock was an underlying reason for device failure.
More than 90% in NYHA class III or IV heart failure
In this study, the mean age was 73 years. More than 90% were in class III or IV heart failure in the 2 weeks prior to TEER. More than half had established coronary artery disease. Other concomitant cardiovascular morbidities, including atrial fibrillation or flutter (65%), prior MI (39%), and prior stroke or transient ischemic attach (> 10%) were well represented.
When those with device success were compared with those with device failure, the risk profile was comparable. The predicted STS (Society of Thoracic Surgeons) mortality for mitral valve repair among these two groups was 14.8% versus 15% (P = 0.97), respectively.
However, those with device failure did have a lower baseline left ventricular ejection fraction (40.7% vs. 42.9%; P = .009) and a greater prevalence of moderate-to-severe or severe MR (96.1% vs. 84.9%; P < 0.001).
The growing experience with TEER means that benefit has now been shown in several complicated MR groups, such as those with severe ventricular dysfunction, renal insufficiency, and obstructive lung disease. This was a rationale for looking at the impact or repairing MR in patients with cardiogenic shock.
It is a pressing question, according to Dr. Alkhouli. He cited studies suggesting that up to 20% of patients hospitalized for cardiogenic shock have at least moderate-to-severe MR. Conversely, cardiogenic shock is not an uncommon finding in patients with MR.
While Dr. Alkhouli acknowledged that the many variables influencing outcome in patients with MR and cardiogenic shock will make a randomized trial “challenging,” many experts echoed this concern and even expressed some skepticism about the potential for an unbiased trial.
Data confirm MR repair is safe during shock
“These data do show that repair of MR is safe in patients safe in patients with cardiogenic shock,” said Anita W. Asgar, MD, an interventional cardiologist associated with the Montreal Heart Institute. She noted that there was a 5- to 6-day delay among the cardiogenic shock patients prior to undergoing MR repair in this analysis, potentially reflecting an elimination of those at very high risk. Similarly, she suggested that many interventionalists are likely to consider multiple variables before proceeding.
As a result, MR repair may not be amenable to randomization in a cardiogenic shock population, given that this decision is not typically undertaken out of the context of multiple variables.
“I am not sure that a clinical trial is ethical,” she said. She would expect that clinicians enrolling patients would only do so on a selective basis.
Alexandra J. Lansky, MD, Director of the Yale Heart and Vascular Research Program, Yale University, New Haven, Conn., also emphasized the difficulty of controlling for variables, such as the duration of cardiogenic shock, that influence decision-making.
Nevertheless, she called the data “very important” in that they at least lend some objective data for deciding whether to intervene a group of “challenging” patients not uncommonly faced in clinical practice.
Dr. Alkhouli reports financial relationships with Abbott Vascular, Boston Scientific, Johnson & Johnson, and Phillips. Dr. Asgar reports financial relationships with Abbott Vascular, Edwards Lifesciences, W.L. Gore & Associates, and Medtronic. Dr. Lasky reports no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
In patients with severe mitral regurgitation (MR) and cardiogenic shock, successful transcatheter edge-to-edge repair (TEER) is associated with a substantial reduction in all-cause mortality and lower morbidity at 1 year, according to an analysis of registry data.
The data from this analysis also confirm that “successful reduction of MR is achievable with TEER in most patients with cardiogenic shock,” reported Mohamad A. Alkhouli, MD, an interventional cardiologist and professor of medicine at the Mayo Clinic, Rochester, Minn.
In those with device success, achieved in 85.6% of patients, all-cause mortality was about 21% lower (34.6% vs. 55.5%; P < .001) at 1 year than in those who were not successfully repaired, according to Dr. Alkhouli, who presented the findings at the Transcatheter Cardiovascular Therapeutics annual meeting in Boston. This translated into a reduction in the hazard ratio for death of nearly 50% (hazard ratio, 0.52; 95% confidence interval, 0.43-0.63).
A similar relative benefit was found for the composite endpoint of mortality and heart failure admissions at 1 year. Whether unadjusted (HR, 0.54; 95% CI, 0.45-0.66) or adjusted (HR, 0.51; 95% CI, 0.42-0.62), risk reductions with successful MR reduction, defined as greater than or equal to 1 grade improvement and a final MR grade of less than or equal to 2+, indicated that major adverse outcomes are reduced by about half.
STS/ACC TCT registry data queried
Drawn from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, 3,797 patients with cardiogenic shock underwent MR repair between November 2013 and December 2021. Outcomes at 1 year were evaluable in 2,773 of these patients. For inclusion, all had to meet at least one of the definitions of cardiogenic shock, such as inotrope use or mechanical circulatory support.
At baseline, 94.5% had a MR severity of at least 3+, and most of these had 4+. Thirty days after treatment, 88.8% had MR severity of 2+ or less, the majority of which had a severity of 1+.
These data address an important question not previously well studied, according to Dr. Alkhouli. In MR patients, cardiogenic shock is associated with a high risk of death, but there has been little evidence that valve repair does not exacerbate, let alone modify, this risk.
These data support the value of intervention, which was performed in almost all patients with MitraClipä (Abbott), the only device available for most of the period in which the registry was queried. However, Dr. Alkhouli cautioned that his data are best considered “hypothesis generating.”
“We need a randomized trial,” he said at the meeting sponsored by the Cardiovascular Research Foundation. He pointed out that this is a complex population for which multiple variables might have skewed results when data are analyzed retrospectively. Not least, those MR patients with cardiogenic shock in the database considered for TEER might well have been relatively healthy and not representative of an unselected population with both MR and cardiogenic shock.
The question might be better answered by the multicenter Canadian trial CAPITAL MINOS, which has just started. Described in an article in the American Heart Journal, it has a planned enrollment of about 150 MR patients with cardiogenic shock randomized to TEER or medical therapy. Results are expected in about 1 year, according to Dr. Alkhouli.
But regarding the present analysis, Dr. Alkhouli did note that sensitivity analyses conducted within his data across risk factors, such as degenerative versus nondegenerative MR, low (< 30%) versus higher left ventricular ejection fraction (LVEF), and presence or absence of an acute coronary syndrome (ACS), consistently supported a benefit from intervention.
Also, cardiogenic shock did not appear to be a factor in device failure, according to Dr. Alkhouli, addressing a potential criticism that cardiogenic shock was an underlying reason for device failure.
More than 90% in NYHA class III or IV heart failure
In this study, the mean age was 73 years. More than 90% were in class III or IV heart failure in the 2 weeks prior to TEER. More than half had established coronary artery disease. Other concomitant cardiovascular morbidities, including atrial fibrillation or flutter (65%), prior MI (39%), and prior stroke or transient ischemic attach (> 10%) were well represented.
When those with device success were compared with those with device failure, the risk profile was comparable. The predicted STS (Society of Thoracic Surgeons) mortality for mitral valve repair among these two groups was 14.8% versus 15% (P = 0.97), respectively.
However, those with device failure did have a lower baseline left ventricular ejection fraction (40.7% vs. 42.9%; P = .009) and a greater prevalence of moderate-to-severe or severe MR (96.1% vs. 84.9%; P < 0.001).
The growing experience with TEER means that benefit has now been shown in several complicated MR groups, such as those with severe ventricular dysfunction, renal insufficiency, and obstructive lung disease. This was a rationale for looking at the impact or repairing MR in patients with cardiogenic shock.
It is a pressing question, according to Dr. Alkhouli. He cited studies suggesting that up to 20% of patients hospitalized for cardiogenic shock have at least moderate-to-severe MR. Conversely, cardiogenic shock is not an uncommon finding in patients with MR.
While Dr. Alkhouli acknowledged that the many variables influencing outcome in patients with MR and cardiogenic shock will make a randomized trial “challenging,” many experts echoed this concern and even expressed some skepticism about the potential for an unbiased trial.
Data confirm MR repair is safe during shock
“These data do show that repair of MR is safe in patients safe in patients with cardiogenic shock,” said Anita W. Asgar, MD, an interventional cardiologist associated with the Montreal Heart Institute. She noted that there was a 5- to 6-day delay among the cardiogenic shock patients prior to undergoing MR repair in this analysis, potentially reflecting an elimination of those at very high risk. Similarly, she suggested that many interventionalists are likely to consider multiple variables before proceeding.
As a result, MR repair may not be amenable to randomization in a cardiogenic shock population, given that this decision is not typically undertaken out of the context of multiple variables.
“I am not sure that a clinical trial is ethical,” she said. She would expect that clinicians enrolling patients would only do so on a selective basis.
Alexandra J. Lansky, MD, Director of the Yale Heart and Vascular Research Program, Yale University, New Haven, Conn., also emphasized the difficulty of controlling for variables, such as the duration of cardiogenic shock, that influence decision-making.
Nevertheless, she called the data “very important” in that they at least lend some objective data for deciding whether to intervene a group of “challenging” patients not uncommonly faced in clinical practice.
Dr. Alkhouli reports financial relationships with Abbott Vascular, Boston Scientific, Johnson & Johnson, and Phillips. Dr. Asgar reports financial relationships with Abbott Vascular, Edwards Lifesciences, W.L. Gore & Associates, and Medtronic. Dr. Lasky reports no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM TCT 2022
Walking intensity and step count are linked to health benefits
Each additional 2,000 steps per day – up to 10,000 – was associated with 8% to 11% fewer deaths and less heart disease and cancer, the researchers found. Walking quickly had an even stronger link to lower health risks.
The findings were reported in JAMA Internal Medicine. In a separate paper, published in JAMA Neurology, the researchers reported associations between walking and reduced risk of dementia.
Moving faster provides a health ‘bonus’
The findings expand on evidence in smaller studies of middle-aged individuals and older women that suggested health benefits from covering less than the widely promoted target of 10,000 steps a day.
The new study supports the ideas that “every step counts” and moving faster provides a health “bonus,” said one of its co-lead authors, Borja del Pozo Cruz, PhD, an associate professor at the University of Southern Denmark, Odense, and a senior researcher in health at the University of Cadiz, Spain.
Dr. Del Pozo Cruz and his coauthors analyzed median daily step counts for 78,500 adults aged 40-79 years in the U.K. Biobank database who agreed to wear an accelerometer for 1 week. Participants’ average age was 61. Fifty-five percent were women and 97% were White.
Steps were categorized as “incidental,” defined as a pace of less than 40 per minute, and “purposeful,” ones taken at the pace of 40 or more per minute. Researchers also calculated peak 30-minute cadence, the average of an individual’s 30 most active minutes in a day.
Participants’ health records were reviewed after 7 years. Each additional 2,000 steps taken was associated with lower all-cause mortality (mean rate of change [MRC] in the hazard ratio, –0.08; 95% confidence interval, –0.11 to –0.06); cardiovascular mortality (MRC, –0.10; 95% CI, –0.15 to –0.06), and cancer mortality (MRC, –0.11; 95% CI, –0.15 to –0.06).
Similar incremental reductions were observed in the incidence of heart disease, defined as fatal and nonfatal coronary heart disease, stroke, and heart failure; and a composite cancer outcome of 13 sites shown to be associated with low physical activity.
Both incidental and purposeful steps were linked to lower rates of mortality and disease. Particularly encouraging, the researchers said, was the benefit associated with incidental steps, which might be more feasible for some individuals than a planned walk.
The association with better outcomes was especially strong for peak-30 cadence, with individuals in the top fifth of intensity having a 34% lower mortality rate compared with those in the bottom fifth – an observation that researchers wrote “reflects the importance of the natural best effort relative to the individual’s capability.”
The analysis adjusted for a variety of factors including age, sex, race, smoking, alcohol use, fruit and vegetable consumption, medication use, family history of cardiovascular disease or cancer, and sleep quality. It also excluded participants who had deaths and illnesses within 2 years of a step assessment to minimize the problem of reverse causation, in which existing health problems cause participants to move less.
Data contribute evidence toward step count recommendations
The data are observational and do not prove cause and effect, the researchers noted. Still, the authors said the study “contributes critical evidence toward step count–based recommendations” for physical activity.
Guidelines of the United States and the World Health Organization recommend 150 minutes of moderately intense activity or 75 minutes of vigorous activity weekly plus strength training twice a week.
Given the proliferation of activity trackers in phones and watches, recommendations based on steps could be especially useful for individuals who don’t intentionally record their physical activity, the researchers wrote.
“It’s nice to have a study that puts some science behind steps counts,” cardiologist Nieca Goldberg, MD, a clinical associate professor of medicine at New York University, and a spokesperson for the American Heart Association, said of the findings.
Particularly important, said Dr. Goldberg, who was not involved in the study, is the lack of a minimum threshold for health benefits, since the 10,000-step target may be daunting for some individuals.
Only one in five participants in this latest study achieved 10,000 steps per day, according to the paper.
The authors wrote that promotion of lower step targets “may provide a more realistic and achievable goal for the general adult population,” and longevity gains “may be maximized simply by shifting away from the least-active end of the step-count distribution.”
Dr. Goldberg put it this way: “Take a walk. Try to aspire to 10,000 steps. But if you can only do 6,000 or 8,000, you get benefit there, too.”
Cathy Handy Marshall, MD, MPH, an assistant professor of oncology at Johns Hopkins University, Baltimore, who was not involved in the new study, said the findings can be used to guide “exercise prescriptions,” but more research is needed to tailor recommendations, particularly for individuals who cannot achieve high step counts.
Dr. Del Pozo Cruz said the findings need to be replicated in other populations.
The study authors, Dr. Goldberg, and Dr. Handy Marshall reported no relevant competing interests.
Each additional 2,000 steps per day – up to 10,000 – was associated with 8% to 11% fewer deaths and less heart disease and cancer, the researchers found. Walking quickly had an even stronger link to lower health risks.
The findings were reported in JAMA Internal Medicine. In a separate paper, published in JAMA Neurology, the researchers reported associations between walking and reduced risk of dementia.
Moving faster provides a health ‘bonus’
The findings expand on evidence in smaller studies of middle-aged individuals and older women that suggested health benefits from covering less than the widely promoted target of 10,000 steps a day.
The new study supports the ideas that “every step counts” and moving faster provides a health “bonus,” said one of its co-lead authors, Borja del Pozo Cruz, PhD, an associate professor at the University of Southern Denmark, Odense, and a senior researcher in health at the University of Cadiz, Spain.
Dr. Del Pozo Cruz and his coauthors analyzed median daily step counts for 78,500 adults aged 40-79 years in the U.K. Biobank database who agreed to wear an accelerometer for 1 week. Participants’ average age was 61. Fifty-five percent were women and 97% were White.
Steps were categorized as “incidental,” defined as a pace of less than 40 per minute, and “purposeful,” ones taken at the pace of 40 or more per minute. Researchers also calculated peak 30-minute cadence, the average of an individual’s 30 most active minutes in a day.
Participants’ health records were reviewed after 7 years. Each additional 2,000 steps taken was associated with lower all-cause mortality (mean rate of change [MRC] in the hazard ratio, –0.08; 95% confidence interval, –0.11 to –0.06); cardiovascular mortality (MRC, –0.10; 95% CI, –0.15 to –0.06), and cancer mortality (MRC, –0.11; 95% CI, –0.15 to –0.06).
Similar incremental reductions were observed in the incidence of heart disease, defined as fatal and nonfatal coronary heart disease, stroke, and heart failure; and a composite cancer outcome of 13 sites shown to be associated with low physical activity.
Both incidental and purposeful steps were linked to lower rates of mortality and disease. Particularly encouraging, the researchers said, was the benefit associated with incidental steps, which might be more feasible for some individuals than a planned walk.
The association with better outcomes was especially strong for peak-30 cadence, with individuals in the top fifth of intensity having a 34% lower mortality rate compared with those in the bottom fifth – an observation that researchers wrote “reflects the importance of the natural best effort relative to the individual’s capability.”
The analysis adjusted for a variety of factors including age, sex, race, smoking, alcohol use, fruit and vegetable consumption, medication use, family history of cardiovascular disease or cancer, and sleep quality. It also excluded participants who had deaths and illnesses within 2 years of a step assessment to minimize the problem of reverse causation, in which existing health problems cause participants to move less.
Data contribute evidence toward step count recommendations
The data are observational and do not prove cause and effect, the researchers noted. Still, the authors said the study “contributes critical evidence toward step count–based recommendations” for physical activity.
Guidelines of the United States and the World Health Organization recommend 150 minutes of moderately intense activity or 75 minutes of vigorous activity weekly plus strength training twice a week.
Given the proliferation of activity trackers in phones and watches, recommendations based on steps could be especially useful for individuals who don’t intentionally record their physical activity, the researchers wrote.
“It’s nice to have a study that puts some science behind steps counts,” cardiologist Nieca Goldberg, MD, a clinical associate professor of medicine at New York University, and a spokesperson for the American Heart Association, said of the findings.
Particularly important, said Dr. Goldberg, who was not involved in the study, is the lack of a minimum threshold for health benefits, since the 10,000-step target may be daunting for some individuals.
Only one in five participants in this latest study achieved 10,000 steps per day, according to the paper.
The authors wrote that promotion of lower step targets “may provide a more realistic and achievable goal for the general adult population,” and longevity gains “may be maximized simply by shifting away from the least-active end of the step-count distribution.”
Dr. Goldberg put it this way: “Take a walk. Try to aspire to 10,000 steps. But if you can only do 6,000 or 8,000, you get benefit there, too.”
Cathy Handy Marshall, MD, MPH, an assistant professor of oncology at Johns Hopkins University, Baltimore, who was not involved in the new study, said the findings can be used to guide “exercise prescriptions,” but more research is needed to tailor recommendations, particularly for individuals who cannot achieve high step counts.
Dr. Del Pozo Cruz said the findings need to be replicated in other populations.
The study authors, Dr. Goldberg, and Dr. Handy Marshall reported no relevant competing interests.
Each additional 2,000 steps per day – up to 10,000 – was associated with 8% to 11% fewer deaths and less heart disease and cancer, the researchers found. Walking quickly had an even stronger link to lower health risks.
The findings were reported in JAMA Internal Medicine. In a separate paper, published in JAMA Neurology, the researchers reported associations between walking and reduced risk of dementia.
Moving faster provides a health ‘bonus’
The findings expand on evidence in smaller studies of middle-aged individuals and older women that suggested health benefits from covering less than the widely promoted target of 10,000 steps a day.
The new study supports the ideas that “every step counts” and moving faster provides a health “bonus,” said one of its co-lead authors, Borja del Pozo Cruz, PhD, an associate professor at the University of Southern Denmark, Odense, and a senior researcher in health at the University of Cadiz, Spain.
Dr. Del Pozo Cruz and his coauthors analyzed median daily step counts for 78,500 adults aged 40-79 years in the U.K. Biobank database who agreed to wear an accelerometer for 1 week. Participants’ average age was 61. Fifty-five percent were women and 97% were White.
Steps were categorized as “incidental,” defined as a pace of less than 40 per minute, and “purposeful,” ones taken at the pace of 40 or more per minute. Researchers also calculated peak 30-minute cadence, the average of an individual’s 30 most active minutes in a day.
Participants’ health records were reviewed after 7 years. Each additional 2,000 steps taken was associated with lower all-cause mortality (mean rate of change [MRC] in the hazard ratio, –0.08; 95% confidence interval, –0.11 to –0.06); cardiovascular mortality (MRC, –0.10; 95% CI, –0.15 to –0.06), and cancer mortality (MRC, –0.11; 95% CI, –0.15 to –0.06).
Similar incremental reductions were observed in the incidence of heart disease, defined as fatal and nonfatal coronary heart disease, stroke, and heart failure; and a composite cancer outcome of 13 sites shown to be associated with low physical activity.
Both incidental and purposeful steps were linked to lower rates of mortality and disease. Particularly encouraging, the researchers said, was the benefit associated with incidental steps, which might be more feasible for some individuals than a planned walk.
The association with better outcomes was especially strong for peak-30 cadence, with individuals in the top fifth of intensity having a 34% lower mortality rate compared with those in the bottom fifth – an observation that researchers wrote “reflects the importance of the natural best effort relative to the individual’s capability.”
The analysis adjusted for a variety of factors including age, sex, race, smoking, alcohol use, fruit and vegetable consumption, medication use, family history of cardiovascular disease or cancer, and sleep quality. It also excluded participants who had deaths and illnesses within 2 years of a step assessment to minimize the problem of reverse causation, in which existing health problems cause participants to move less.
Data contribute evidence toward step count recommendations
The data are observational and do not prove cause and effect, the researchers noted. Still, the authors said the study “contributes critical evidence toward step count–based recommendations” for physical activity.
Guidelines of the United States and the World Health Organization recommend 150 minutes of moderately intense activity or 75 minutes of vigorous activity weekly plus strength training twice a week.
Given the proliferation of activity trackers in phones and watches, recommendations based on steps could be especially useful for individuals who don’t intentionally record their physical activity, the researchers wrote.
“It’s nice to have a study that puts some science behind steps counts,” cardiologist Nieca Goldberg, MD, a clinical associate professor of medicine at New York University, and a spokesperson for the American Heart Association, said of the findings.
Particularly important, said Dr. Goldberg, who was not involved in the study, is the lack of a minimum threshold for health benefits, since the 10,000-step target may be daunting for some individuals.
Only one in five participants in this latest study achieved 10,000 steps per day, according to the paper.
The authors wrote that promotion of lower step targets “may provide a more realistic and achievable goal for the general adult population,” and longevity gains “may be maximized simply by shifting away from the least-active end of the step-count distribution.”
Dr. Goldberg put it this way: “Take a walk. Try to aspire to 10,000 steps. But if you can only do 6,000 or 8,000, you get benefit there, too.”
Cathy Handy Marshall, MD, MPH, an assistant professor of oncology at Johns Hopkins University, Baltimore, who was not involved in the new study, said the findings can be used to guide “exercise prescriptions,” but more research is needed to tailor recommendations, particularly for individuals who cannot achieve high step counts.
Dr. Del Pozo Cruz said the findings need to be replicated in other populations.
The study authors, Dr. Goldberg, and Dr. Handy Marshall reported no relevant competing interests.
FROM JAMA INTERNAL MEDICINE
TBI is an unrecognized risk factor for cardiovascular disease
(CVD). More severe TBI is associated with higher risk of CVD, new research shows.
Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.
The study was published online in JAMA Neurology.
Novel data
Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.
While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.
The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.
In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).
TBIs of all severities were associated with the individual components of the composite outcome, except penetrating TBI and CVD death.
“The association of TBI with subsequent CVD was not attenuated in multivariable models, suggesting that TBI may be accounting for risk that is independent from the other variables,” Dr. Stewart and colleagues wrote.
They noted that the risk was highest shortly after injury, but TBI remained significantly associated with CVD for years after the initial insult.
Why TBI may raise the risk of subsequent CVD remains unclear.
It’s possible that patients with TBI develop more traditional risk factors for CVD through time than do patients without TBI. A study in mice found that TBI led to increased rates of atherosclerosis, the researchers said.
An additional mechanism may be disruption of autonomic regulation, which has been known to occur after TBI.
Another potential pathway is through mental health diagnoses, such as posttraumatic stress disorder; a large body of work has identified associations between PTSD and CVD, including among post-9/11 veterans.
Further work is needed to determine how this risk can be modified to improve outcomes for post-9/11–era veterans, the researchers write.
Unrecognized CVD risk factor?
Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”
“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.
In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”
“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.
The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(CVD). More severe TBI is associated with higher risk of CVD, new research shows.
Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.
The study was published online in JAMA Neurology.
Novel data
Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.
While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.
The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.
In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).
TBIs of all severities were associated with the individual components of the composite outcome, except penetrating TBI and CVD death.
“The association of TBI with subsequent CVD was not attenuated in multivariable models, suggesting that TBI may be accounting for risk that is independent from the other variables,” Dr. Stewart and colleagues wrote.
They noted that the risk was highest shortly after injury, but TBI remained significantly associated with CVD for years after the initial insult.
Why TBI may raise the risk of subsequent CVD remains unclear.
It’s possible that patients with TBI develop more traditional risk factors for CVD through time than do patients without TBI. A study in mice found that TBI led to increased rates of atherosclerosis, the researchers said.
An additional mechanism may be disruption of autonomic regulation, which has been known to occur after TBI.
Another potential pathway is through mental health diagnoses, such as posttraumatic stress disorder; a large body of work has identified associations between PTSD and CVD, including among post-9/11 veterans.
Further work is needed to determine how this risk can be modified to improve outcomes for post-9/11–era veterans, the researchers write.
Unrecognized CVD risk factor?
Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”
“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.
In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”
“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.
The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(CVD). More severe TBI is associated with higher risk of CVD, new research shows.
Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.
The study was published online in JAMA Neurology.
Novel data
Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.
While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.
The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.
In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).
TBIs of all severities were associated with the individual components of the composite outcome, except penetrating TBI and CVD death.
“The association of TBI with subsequent CVD was not attenuated in multivariable models, suggesting that TBI may be accounting for risk that is independent from the other variables,” Dr. Stewart and colleagues wrote.
They noted that the risk was highest shortly after injury, but TBI remained significantly associated with CVD for years after the initial insult.
Why TBI may raise the risk of subsequent CVD remains unclear.
It’s possible that patients with TBI develop more traditional risk factors for CVD through time than do patients without TBI. A study in mice found that TBI led to increased rates of atherosclerosis, the researchers said.
An additional mechanism may be disruption of autonomic regulation, which has been known to occur after TBI.
Another potential pathway is through mental health diagnoses, such as posttraumatic stress disorder; a large body of work has identified associations between PTSD and CVD, including among post-9/11 veterans.
Further work is needed to determine how this risk can be modified to improve outcomes for post-9/11–era veterans, the researchers write.
Unrecognized CVD risk factor?
Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”
“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.
In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”
“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.
The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
PARADISE-MI results obscured as post hoc analysis finds flaws
A post hoc analysis of the PARADISE-MI trial, although not intended to alter the conclusions generated by the published data, suggests that clinically relevant benefits were obscured, providing the basis for recommending different analyses for future studies that are more suited to capture the most clinically significant endpoints.
“What these data show us is that we need clinical trial designs moving towards more pragmatic information that better reflect clinical practice,” reported Otavio Berwanger, MD, PhD, director of the Academic Research Organization at Hospital Israelita Albert Einstein, São Paulo, Brazil.
The reevaluation of the PARADISE-MI data, presented at the annual congress of the European Society of Cardiology in Barcelona, was based on a win ratio analysis and on the inclusion of investigator-reported endpoints, not just adjudicated events. Both appear to reveal clinically meaningful benefits not reflected in the published study, according to Dr. Berwanger.
In PARADISE-MI, which was published in the New England Journal of Medicine last year, more than 5,500 patients were randomized to the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan or the ACE inhibitor ramipril after a myocardial infarction. A reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both were required for enrollment.
For the primary composite outcomes of death from cardiovascular (CV) causes or incident heart failure, the ARNI had a 10% numerical advantage, but it did not reach statistical significance (hazard ratio [HR], 0.90; P = .17).
“PARADISE-MI was a neutral trial. This post hoc analysis will not change that result,” Dr. Berwanger emphasized. However, the post hoc analysis does provide a basis for exploring why conventional trial designs might not be providing answers that are relevant and helpful for clinical practice.
New analysis provides positive trial result
When the data from PARADISE-MI are reevaluated in a hierarchical win ratio analysis with CV death serving as the most severe and important outcome, the principal conclusion changes. Whether events are reevaluated in this format by the clinical events committee (CEC) or by investigators, there is a greater number of total wins than total losses for the ARNI. Combined, sacubitril/valsartan was associated with a win ratio of 1.17 (95% confidence interval, 1.03-1.33; P = 0.015) over ramipril.
Using a sports analogy, Dr. Berwanger explained that the win ratio analysis divides the total number of wins to the total number of losses to provide a much more clinically relevant approach to keeping score. It also used a hierarchical analysis so that the most serious and important events are considered first.
In addition to CV death, this analysis included first hospitalization for heart failure and first outpatient heart failure events. CEC-defined events and events reported by investigators were evaluated separately.
The ARNI had more wins than losses in every category for all outcomes, whether CEC adjudicated or investigator reported, but most of this benefit was generated by the endpoint of CEC-adjudicated CV deaths. This accounted for 36.9% of all events (investigator-documented CV death accounted for 0.7%). This is important because PARADISE-MI, like many standard trials, was conducted on a time-to-primary event basis.
“In this type of analysis, the first event is what counts. Usually time-to-first-event analyses are dominated by nonfatal events,” Dr. Berwanger explained. He believes that placing more weight on the most serious events results in an emphasis on what outcomes are of greatest clinical interest.
In addition, Dr. Berwanger argued that it is important to consider investigator-reported events, not just CEC-adjudicated events. While adjudicated events improve the rigor of the data, Dr. Berwanger suggested it omits outcomes with which clinicians are most concerned.
Investigator, adjudicated outcomes differ
Again, using PARADISE-MI as an example, he reevaluated the primary outcome based on investigator reports. When investigator-reported events are included, the number of events increased in both the ARNI (443 vs. 338) and ramipril (516 vs. 373) arms, but the advantage of the ARNI over the ACE inhibitors now reached statistical significance (HR, 0.85; P = .01).
“The data suggest that maybe we should find definitions for adjudication that are closer to clinical judgment in the real world and clinical practice,” Dr. Berwanger said.
One possible explanation for the neutral result in PARADISE-MI is that benefit of an ARNI over an ACE inhibitor would only be expected in those at risk for progressive left ventricular dysfunction, and it is likely that a substantial proportion of patients enrolled in this trial recovered, according to Johann Bauersachs, MD, PhD, professor and head of cardiology at Hannover (Germany) Medical School.
“You cannot predict which patients with reduced LV function following an MI will go on to chronic remodeling and which will recover,” said Dr. Bauersachs, who was an ESC-invited discussant of Dr. Berwanger’s post hoc analysis.
He agreed that Dr. Berwanger has raised several important issues in standard trial design that might have prevented PARADISE-MI from showing a benefit from an ARNI, but he pointed out that there are other potential issues, such as the low use of mineralocorticoid antagonists in PARADISE-MI, that may have skewed results.
However, he agreed generally with the premise that there is a need for trial design likely to generate more clinically useful information.
“We have now seen the win-ratio approach used in several studies,” said Dr. Bauersachs, citing in particular the EMPULSE trial presented at the 2022 meeting of the American College of Cardiology. “It is a very useful tool, and I think we will be seeing it used more in the future.”
However, he indicated that the issues raised by Dr. Berwanger are not necessarily easily resolved. Dr. Bauersachs endorsed the effort to consider trial designs that generate data that are more immediately clinically applicable but suggested that different types of designs may be required for different types of clinical questions.
Dr. Berwanger reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, Servier, and Novartis, which provided funding for the PARADISE-MI trial. Dr. Bauersachs reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Cardior, Corvia, CVRx, Novartis, Pfizer, Vifor, and Zoll.
A post hoc analysis of the PARADISE-MI trial, although not intended to alter the conclusions generated by the published data, suggests that clinically relevant benefits were obscured, providing the basis for recommending different analyses for future studies that are more suited to capture the most clinically significant endpoints.
“What these data show us is that we need clinical trial designs moving towards more pragmatic information that better reflect clinical practice,” reported Otavio Berwanger, MD, PhD, director of the Academic Research Organization at Hospital Israelita Albert Einstein, São Paulo, Brazil.
The reevaluation of the PARADISE-MI data, presented at the annual congress of the European Society of Cardiology in Barcelona, was based on a win ratio analysis and on the inclusion of investigator-reported endpoints, not just adjudicated events. Both appear to reveal clinically meaningful benefits not reflected in the published study, according to Dr. Berwanger.
In PARADISE-MI, which was published in the New England Journal of Medicine last year, more than 5,500 patients were randomized to the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan or the ACE inhibitor ramipril after a myocardial infarction. A reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both were required for enrollment.
For the primary composite outcomes of death from cardiovascular (CV) causes or incident heart failure, the ARNI had a 10% numerical advantage, but it did not reach statistical significance (hazard ratio [HR], 0.90; P = .17).
“PARADISE-MI was a neutral trial. This post hoc analysis will not change that result,” Dr. Berwanger emphasized. However, the post hoc analysis does provide a basis for exploring why conventional trial designs might not be providing answers that are relevant and helpful for clinical practice.
New analysis provides positive trial result
When the data from PARADISE-MI are reevaluated in a hierarchical win ratio analysis with CV death serving as the most severe and important outcome, the principal conclusion changes. Whether events are reevaluated in this format by the clinical events committee (CEC) or by investigators, there is a greater number of total wins than total losses for the ARNI. Combined, sacubitril/valsartan was associated with a win ratio of 1.17 (95% confidence interval, 1.03-1.33; P = 0.015) over ramipril.
Using a sports analogy, Dr. Berwanger explained that the win ratio analysis divides the total number of wins to the total number of losses to provide a much more clinically relevant approach to keeping score. It also used a hierarchical analysis so that the most serious and important events are considered first.
In addition to CV death, this analysis included first hospitalization for heart failure and first outpatient heart failure events. CEC-defined events and events reported by investigators were evaluated separately.
The ARNI had more wins than losses in every category for all outcomes, whether CEC adjudicated or investigator reported, but most of this benefit was generated by the endpoint of CEC-adjudicated CV deaths. This accounted for 36.9% of all events (investigator-documented CV death accounted for 0.7%). This is important because PARADISE-MI, like many standard trials, was conducted on a time-to-primary event basis.
“In this type of analysis, the first event is what counts. Usually time-to-first-event analyses are dominated by nonfatal events,” Dr. Berwanger explained. He believes that placing more weight on the most serious events results in an emphasis on what outcomes are of greatest clinical interest.
In addition, Dr. Berwanger argued that it is important to consider investigator-reported events, not just CEC-adjudicated events. While adjudicated events improve the rigor of the data, Dr. Berwanger suggested it omits outcomes with which clinicians are most concerned.
Investigator, adjudicated outcomes differ
Again, using PARADISE-MI as an example, he reevaluated the primary outcome based on investigator reports. When investigator-reported events are included, the number of events increased in both the ARNI (443 vs. 338) and ramipril (516 vs. 373) arms, but the advantage of the ARNI over the ACE inhibitors now reached statistical significance (HR, 0.85; P = .01).
“The data suggest that maybe we should find definitions for adjudication that are closer to clinical judgment in the real world and clinical practice,” Dr. Berwanger said.
One possible explanation for the neutral result in PARADISE-MI is that benefit of an ARNI over an ACE inhibitor would only be expected in those at risk for progressive left ventricular dysfunction, and it is likely that a substantial proportion of patients enrolled in this trial recovered, according to Johann Bauersachs, MD, PhD, professor and head of cardiology at Hannover (Germany) Medical School.
“You cannot predict which patients with reduced LV function following an MI will go on to chronic remodeling and which will recover,” said Dr. Bauersachs, who was an ESC-invited discussant of Dr. Berwanger’s post hoc analysis.
He agreed that Dr. Berwanger has raised several important issues in standard trial design that might have prevented PARADISE-MI from showing a benefit from an ARNI, but he pointed out that there are other potential issues, such as the low use of mineralocorticoid antagonists in PARADISE-MI, that may have skewed results.
However, he agreed generally with the premise that there is a need for trial design likely to generate more clinically useful information.
“We have now seen the win-ratio approach used in several studies,” said Dr. Bauersachs, citing in particular the EMPULSE trial presented at the 2022 meeting of the American College of Cardiology. “It is a very useful tool, and I think we will be seeing it used more in the future.”
However, he indicated that the issues raised by Dr. Berwanger are not necessarily easily resolved. Dr. Bauersachs endorsed the effort to consider trial designs that generate data that are more immediately clinically applicable but suggested that different types of designs may be required for different types of clinical questions.
Dr. Berwanger reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, Servier, and Novartis, which provided funding for the PARADISE-MI trial. Dr. Bauersachs reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Cardior, Corvia, CVRx, Novartis, Pfizer, Vifor, and Zoll.
A post hoc analysis of the PARADISE-MI trial, although not intended to alter the conclusions generated by the published data, suggests that clinically relevant benefits were obscured, providing the basis for recommending different analyses for future studies that are more suited to capture the most clinically significant endpoints.
“What these data show us is that we need clinical trial designs moving towards more pragmatic information that better reflect clinical practice,” reported Otavio Berwanger, MD, PhD, director of the Academic Research Organization at Hospital Israelita Albert Einstein, São Paulo, Brazil.
The reevaluation of the PARADISE-MI data, presented at the annual congress of the European Society of Cardiology in Barcelona, was based on a win ratio analysis and on the inclusion of investigator-reported endpoints, not just adjudicated events. Both appear to reveal clinically meaningful benefits not reflected in the published study, according to Dr. Berwanger.
In PARADISE-MI, which was published in the New England Journal of Medicine last year, more than 5,500 patients were randomized to the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan or the ACE inhibitor ramipril after a myocardial infarction. A reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both were required for enrollment.
For the primary composite outcomes of death from cardiovascular (CV) causes or incident heart failure, the ARNI had a 10% numerical advantage, but it did not reach statistical significance (hazard ratio [HR], 0.90; P = .17).
“PARADISE-MI was a neutral trial. This post hoc analysis will not change that result,” Dr. Berwanger emphasized. However, the post hoc analysis does provide a basis for exploring why conventional trial designs might not be providing answers that are relevant and helpful for clinical practice.
New analysis provides positive trial result
When the data from PARADISE-MI are reevaluated in a hierarchical win ratio analysis with CV death serving as the most severe and important outcome, the principal conclusion changes. Whether events are reevaluated in this format by the clinical events committee (CEC) or by investigators, there is a greater number of total wins than total losses for the ARNI. Combined, sacubitril/valsartan was associated with a win ratio of 1.17 (95% confidence interval, 1.03-1.33; P = 0.015) over ramipril.
Using a sports analogy, Dr. Berwanger explained that the win ratio analysis divides the total number of wins to the total number of losses to provide a much more clinically relevant approach to keeping score. It also used a hierarchical analysis so that the most serious and important events are considered first.
In addition to CV death, this analysis included first hospitalization for heart failure and first outpatient heart failure events. CEC-defined events and events reported by investigators were evaluated separately.
The ARNI had more wins than losses in every category for all outcomes, whether CEC adjudicated or investigator reported, but most of this benefit was generated by the endpoint of CEC-adjudicated CV deaths. This accounted for 36.9% of all events (investigator-documented CV death accounted for 0.7%). This is important because PARADISE-MI, like many standard trials, was conducted on a time-to-primary event basis.
“In this type of analysis, the first event is what counts. Usually time-to-first-event analyses are dominated by nonfatal events,” Dr. Berwanger explained. He believes that placing more weight on the most serious events results in an emphasis on what outcomes are of greatest clinical interest.
In addition, Dr. Berwanger argued that it is important to consider investigator-reported events, not just CEC-adjudicated events. While adjudicated events improve the rigor of the data, Dr. Berwanger suggested it omits outcomes with which clinicians are most concerned.
Investigator, adjudicated outcomes differ
Again, using PARADISE-MI as an example, he reevaluated the primary outcome based on investigator reports. When investigator-reported events are included, the number of events increased in both the ARNI (443 vs. 338) and ramipril (516 vs. 373) arms, but the advantage of the ARNI over the ACE inhibitors now reached statistical significance (HR, 0.85; P = .01).
“The data suggest that maybe we should find definitions for adjudication that are closer to clinical judgment in the real world and clinical practice,” Dr. Berwanger said.
One possible explanation for the neutral result in PARADISE-MI is that benefit of an ARNI over an ACE inhibitor would only be expected in those at risk for progressive left ventricular dysfunction, and it is likely that a substantial proportion of patients enrolled in this trial recovered, according to Johann Bauersachs, MD, PhD, professor and head of cardiology at Hannover (Germany) Medical School.
“You cannot predict which patients with reduced LV function following an MI will go on to chronic remodeling and which will recover,” said Dr. Bauersachs, who was an ESC-invited discussant of Dr. Berwanger’s post hoc analysis.
He agreed that Dr. Berwanger has raised several important issues in standard trial design that might have prevented PARADISE-MI from showing a benefit from an ARNI, but he pointed out that there are other potential issues, such as the low use of mineralocorticoid antagonists in PARADISE-MI, that may have skewed results.
However, he agreed generally with the premise that there is a need for trial design likely to generate more clinically useful information.
“We have now seen the win-ratio approach used in several studies,” said Dr. Bauersachs, citing in particular the EMPULSE trial presented at the 2022 meeting of the American College of Cardiology. “It is a very useful tool, and I think we will be seeing it used more in the future.”
However, he indicated that the issues raised by Dr. Berwanger are not necessarily easily resolved. Dr. Bauersachs endorsed the effort to consider trial designs that generate data that are more immediately clinically applicable but suggested that different types of designs may be required for different types of clinical questions.
Dr. Berwanger reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, Servier, and Novartis, which provided funding for the PARADISE-MI trial. Dr. Bauersachs reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Cardior, Corvia, CVRx, Novartis, Pfizer, Vifor, and Zoll.
FROM ESC CONGRESS 2022
Dietary change tops for reducing CVD risk in stage 1 hypertension
Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.
Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.
“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.
“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
Be proactive
“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.
“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.
The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg.
The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.
Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.
The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
Even small changes can help
“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.
“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.
“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.
“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.
Dr. Wallace noted that diet changes don’t have to be drastic.
“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.
“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.
The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.
Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.
“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.
“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
Be proactive
“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.
“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.
The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg.
The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.
Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.
The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
Even small changes can help
“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.
“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.
“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.
“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.
Dr. Wallace noted that diet changes don’t have to be drastic.
“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.
“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.
The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.
Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.
“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.
“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
Be proactive
“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.
“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.
The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg.
The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.
Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.
The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
Even small changes can help
“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.
“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.
“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.
“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.
Dr. Wallace noted that diet changes don’t have to be drastic.
“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.
“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.
The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
‘Spectacular’ polypill results also puzzle docs
But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.
How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?
Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.
As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
A matter of adherence?
In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.
Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).
Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)
The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).
“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.
“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.
Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.
In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.
Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.
One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.
Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.
Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.
When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”
“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
Can the results be replicated?
Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”
“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.
Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.
Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.
To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”
“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.
In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.
“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”
Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.
But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.
“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”
For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.
Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.
Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.
Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.
Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.
“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.
That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.
The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.”
The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.
A version of this article first appeared on Medscape.com.
But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.
How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?
Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.
As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
A matter of adherence?
In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.
Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).
Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)
The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).
“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.
“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.
Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.
In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.
Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.
One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.
Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.
Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.
When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”
“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
Can the results be replicated?
Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”
“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.
Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.
Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.
To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”
“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.
In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.
“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”
Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.
But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.
“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”
For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.
Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.
Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.
Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.
Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.
“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.
That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.
The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.”
The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.
A version of this article first appeared on Medscape.com.
But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.
How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?
Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.
As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
A matter of adherence?
In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.
Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).
Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)
The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).
“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.
“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.
Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.
In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.
Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.
One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.
Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.
Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.
When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”
“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
Can the results be replicated?
Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”
“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.
Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.
Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.
To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”
“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.
In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.
“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”
Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.
But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.
“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”
For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.
Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.
Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.
Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.
Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.
“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.
That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.
The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.”
The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.
A version of this article first appeared on Medscape.com.
Test Lp(a) levels to inform ASCVD management: NLA statement
Lipoprotein(a) (Lp[a]) levels should be measured in clinical practice to refine risk prediction for atherosclerotic cardiovascular disease (ASCVD) and inform treatment decisions, even if they cannot yet be lowered directly, recommends the National Lipid Association (NLA) in a scientific statement.
The statement was published in the Journal of Clinical Lipidology.
Don P. Wilson, MD, department of pediatric endocrinology and diabetes, Cook Children’s Medical Center, Fort Worth, Tex., told this news organization that lipoprotein(a) is a “very timely subject.”
“The question in the scientific community is: What role does that particular biomarker play in terms of causing serious heart disease, stroke, and calcification of the aortic valve?”
“It’s pretty clear that, in and of itself, it actually can contribute and or cause any of those conditions,” he added. “The thing that’s then sort of problematic is that we don’t have a specific treatment to lower” Lp(a).
However, Dr. Wilson said that the statement underlines it is “still worth knowing” an individual’s Lp(a) concentrations because the risk with increased levels is “even higher for those people who have other conditions, such as metabolic disease or diabetes or high cholesterol.”
There are nevertheless several drugs in phase 2 and 3 clinical trials that appear to have the potential to significantly lower Lp(a) levels.
“I’m very excited,” said Dr. Wilson, noting that, so far, the drugs seem to be “quite safe,” and the currently available data suggest that they can “reduce Lp(a) levels by about 90%, which is huge.”
“That’s better than any drug we’ve got on the market.”
He cautioned, however, that it is going to take time after the drugs are approved to see the real benefits and risks once they start being used in very large populations, given that raised Lp(a) concentrations are present in about 20% of the world population.
The publication of the NLA statement coincides with a similar one from the European Atherosclerosis Society presented at the European Society of Cardiology Congress 2022 on Aug. 29, and published simultaneously in the European Heart Journal.
Coauthor of the EAS statement, Alberico L. Catapano, MD, PhD, professor of pharmacology at the University of Milan, and past president of the EAS, said that there are many areas in which the two statements are “in complete agreement.”
“However, the spirit of the documents is different,” he continued, chief among them being that the EAS statement focuses on the “global risk” of ASCVD and provides a risk calculator to help balance the risk increase with Lp(a) with that from other factors.
Another is that increased Lp(a) levels are recognized as being on a continuum in terms of their risk, such that there is no level at which raised concentrations can be deemed safe.
Dr. Wilson agreed with Dr. Capatano’s assessment, saying that the EAS statement takes current scientific observations “a step further,” in part by emphasizing that Lp(a) is “only one piece of the puzzle” for determining an individuals’ cardiovascular risk.
This will have huge implications for the conversations clinicians have with patients over shared decision-making, Dr. Wilson added.
Nevertheless, Dr. Catapano underlined to this news organization that “both documents are very important” in terms of the need to “raise awareness about a causal risk factor” for cardiovascular disease as well as that modifying Lp(a) concentrations “will probably reduce the risk.”
The statement from the NLA builds on the association’s prior Recommendations for the Patient-Centered Management of Dyslipidemia, published in two parts in 2014 and 2015, and comes to many of the same conclusions as the EAS statement.
It explains that apolipoprotein A, a component of Lp(a) attached to apolipoprotein B, has “unique” properties that promote the “initiation and progression of atherosclerosis and calcific valvular aortic stenosis, through endothelial dysfunction and proinflammatory responses, and pro-osteogenic effects promoting calcification.”
This, in turn, has the potential to cause myocardial infarction and ischemic stroke, the authors note.
This has been confirmed in meta-analyses of prospective, population-based studies showing a high risk for MI, coronary heart disease, and ischemic stroke with high Lp(a) levels, the statement adds.
Moreover, large genetic studies have confirmed that Lp(a) is a causal factor, independent of low-density lipoprotein cholesterol levels, for MI, ischemic stroke, valvular aortic stenosis, coronary artery stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause mortality.
Like the authors of the EAS statement, the NLA statement authors underline that the measurement of Lp(a) is “currently not standardized or harmonized,” and there is insufficient evidence on the utility of different cut-offs for risk based on age, gender, ethnicity, or the presence of comorbid conditions.
However, they do suggest that Lp(a) levels greater than 50 mg/dL (> 100 nmol/L) may be considered as a risk-enhancing factor favoring the initiation of statin therapy, although they note that the threshold could be threefold higher in African American individuals.
Despite these reservations, the authors say that Lp(a) testing “is reasonable” for refining the risk assessment of ASCVD in the first-degree relatives of people with premature ASCVD and those with a personal history of premature disease as well as in individuals with primary severe hypercholesterolemia.
Testing also “may be reasonable” to “aid in the clinician-patient discussion about whether to prescribe a statin” in people aged 40-75 years with borderline 10-year ASCVD risk, defined as 5%-7.4%, as well as in other equivocal clinical situations.
In terms of what to do in an individual with raised Lp(a) levels, the statement notes that lifestyle therapy and statins do not decrease Lp(a).
Although lomitapide (Juxtapid) and proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors both lower levels of the lipoprotein, the former is “not recommended for ASCVD risk reduction,” whereas the impact of the latter on ASCVD risk reduction via Lp(a) reduction “remains undetermined.”
Several experimental agents are currently under investigation to reduce Lp(a) levels, including SLN360 (Silence Therapeutics), and AKCEA-APO(a)-LRX (Akcea Therapeutics/Ionis Pharmaceuticals).
In the meantime, the authors say it is reasonable to use Lp(a) as a “risk-enhancing factor” for the initiation of moderate- or high-intensity statins in the primary prevention of ASCVD and to consider the addition of ezetimibe and/or PCSK9 inhibitors in high- and very high–risk patients already on maximally tolerated statin therapy.
Finally, the authors recognize the need for “additional evidence” to support clinical practice. In the absence of a randomized clinical trial of Lp(a) lowering in those who are at risk for ASCVD, they note that “several important unanswered questions remain.”
These include: “Is it reasonable to recommend universal testing of Lp(a) in everyone regardless of family history or health status at least once to help encourage healthy habits and inform clinical decision-making?” “Will earlier testing and effective interventions help to improve outcomes?”
Alongside more evidence in children, the authors also emphasize that “additional data are urgently needed in Blacks, South Asians, and those of Hispanic descent.”
No funding declared. Dr. Wilson declares relationships with Osler Institute, Merck Sharp & Dohm, Novo Nordisk, and Alexion Pharmaceuticals. Other authors also declare numerous relationships. Dr. Catapano declares a relationship with Novartis.
A version of this article first appeared on Medscape.com.
Lipoprotein(a) (Lp[a]) levels should be measured in clinical practice to refine risk prediction for atherosclerotic cardiovascular disease (ASCVD) and inform treatment decisions, even if they cannot yet be lowered directly, recommends the National Lipid Association (NLA) in a scientific statement.
The statement was published in the Journal of Clinical Lipidology.
Don P. Wilson, MD, department of pediatric endocrinology and diabetes, Cook Children’s Medical Center, Fort Worth, Tex., told this news organization that lipoprotein(a) is a “very timely subject.”
“The question in the scientific community is: What role does that particular biomarker play in terms of causing serious heart disease, stroke, and calcification of the aortic valve?”
“It’s pretty clear that, in and of itself, it actually can contribute and or cause any of those conditions,” he added. “The thing that’s then sort of problematic is that we don’t have a specific treatment to lower” Lp(a).
However, Dr. Wilson said that the statement underlines it is “still worth knowing” an individual’s Lp(a) concentrations because the risk with increased levels is “even higher for those people who have other conditions, such as metabolic disease or diabetes or high cholesterol.”
There are nevertheless several drugs in phase 2 and 3 clinical trials that appear to have the potential to significantly lower Lp(a) levels.
“I’m very excited,” said Dr. Wilson, noting that, so far, the drugs seem to be “quite safe,” and the currently available data suggest that they can “reduce Lp(a) levels by about 90%, which is huge.”
“That’s better than any drug we’ve got on the market.”
He cautioned, however, that it is going to take time after the drugs are approved to see the real benefits and risks once they start being used in very large populations, given that raised Lp(a) concentrations are present in about 20% of the world population.
The publication of the NLA statement coincides with a similar one from the European Atherosclerosis Society presented at the European Society of Cardiology Congress 2022 on Aug. 29, and published simultaneously in the European Heart Journal.
Coauthor of the EAS statement, Alberico L. Catapano, MD, PhD, professor of pharmacology at the University of Milan, and past president of the EAS, said that there are many areas in which the two statements are “in complete agreement.”
“However, the spirit of the documents is different,” he continued, chief among them being that the EAS statement focuses on the “global risk” of ASCVD and provides a risk calculator to help balance the risk increase with Lp(a) with that from other factors.
Another is that increased Lp(a) levels are recognized as being on a continuum in terms of their risk, such that there is no level at which raised concentrations can be deemed safe.
Dr. Wilson agreed with Dr. Capatano’s assessment, saying that the EAS statement takes current scientific observations “a step further,” in part by emphasizing that Lp(a) is “only one piece of the puzzle” for determining an individuals’ cardiovascular risk.
This will have huge implications for the conversations clinicians have with patients over shared decision-making, Dr. Wilson added.
Nevertheless, Dr. Catapano underlined to this news organization that “both documents are very important” in terms of the need to “raise awareness about a causal risk factor” for cardiovascular disease as well as that modifying Lp(a) concentrations “will probably reduce the risk.”
The statement from the NLA builds on the association’s prior Recommendations for the Patient-Centered Management of Dyslipidemia, published in two parts in 2014 and 2015, and comes to many of the same conclusions as the EAS statement.
It explains that apolipoprotein A, a component of Lp(a) attached to apolipoprotein B, has “unique” properties that promote the “initiation and progression of atherosclerosis and calcific valvular aortic stenosis, through endothelial dysfunction and proinflammatory responses, and pro-osteogenic effects promoting calcification.”
This, in turn, has the potential to cause myocardial infarction and ischemic stroke, the authors note.
This has been confirmed in meta-analyses of prospective, population-based studies showing a high risk for MI, coronary heart disease, and ischemic stroke with high Lp(a) levels, the statement adds.
Moreover, large genetic studies have confirmed that Lp(a) is a causal factor, independent of low-density lipoprotein cholesterol levels, for MI, ischemic stroke, valvular aortic stenosis, coronary artery stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause mortality.
Like the authors of the EAS statement, the NLA statement authors underline that the measurement of Lp(a) is “currently not standardized or harmonized,” and there is insufficient evidence on the utility of different cut-offs for risk based on age, gender, ethnicity, or the presence of comorbid conditions.
However, they do suggest that Lp(a) levels greater than 50 mg/dL (> 100 nmol/L) may be considered as a risk-enhancing factor favoring the initiation of statin therapy, although they note that the threshold could be threefold higher in African American individuals.
Despite these reservations, the authors say that Lp(a) testing “is reasonable” for refining the risk assessment of ASCVD in the first-degree relatives of people with premature ASCVD and those with a personal history of premature disease as well as in individuals with primary severe hypercholesterolemia.
Testing also “may be reasonable” to “aid in the clinician-patient discussion about whether to prescribe a statin” in people aged 40-75 years with borderline 10-year ASCVD risk, defined as 5%-7.4%, as well as in other equivocal clinical situations.
In terms of what to do in an individual with raised Lp(a) levels, the statement notes that lifestyle therapy and statins do not decrease Lp(a).
Although lomitapide (Juxtapid) and proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors both lower levels of the lipoprotein, the former is “not recommended for ASCVD risk reduction,” whereas the impact of the latter on ASCVD risk reduction via Lp(a) reduction “remains undetermined.”
Several experimental agents are currently under investigation to reduce Lp(a) levels, including SLN360 (Silence Therapeutics), and AKCEA-APO(a)-LRX (Akcea Therapeutics/Ionis Pharmaceuticals).
In the meantime, the authors say it is reasonable to use Lp(a) as a “risk-enhancing factor” for the initiation of moderate- or high-intensity statins in the primary prevention of ASCVD and to consider the addition of ezetimibe and/or PCSK9 inhibitors in high- and very high–risk patients already on maximally tolerated statin therapy.
Finally, the authors recognize the need for “additional evidence” to support clinical practice. In the absence of a randomized clinical trial of Lp(a) lowering in those who are at risk for ASCVD, they note that “several important unanswered questions remain.”
These include: “Is it reasonable to recommend universal testing of Lp(a) in everyone regardless of family history or health status at least once to help encourage healthy habits and inform clinical decision-making?” “Will earlier testing and effective interventions help to improve outcomes?”
Alongside more evidence in children, the authors also emphasize that “additional data are urgently needed in Blacks, South Asians, and those of Hispanic descent.”
No funding declared. Dr. Wilson declares relationships with Osler Institute, Merck Sharp & Dohm, Novo Nordisk, and Alexion Pharmaceuticals. Other authors also declare numerous relationships. Dr. Catapano declares a relationship with Novartis.
A version of this article first appeared on Medscape.com.
Lipoprotein(a) (Lp[a]) levels should be measured in clinical practice to refine risk prediction for atherosclerotic cardiovascular disease (ASCVD) and inform treatment decisions, even if they cannot yet be lowered directly, recommends the National Lipid Association (NLA) in a scientific statement.
The statement was published in the Journal of Clinical Lipidology.
Don P. Wilson, MD, department of pediatric endocrinology and diabetes, Cook Children’s Medical Center, Fort Worth, Tex., told this news organization that lipoprotein(a) is a “very timely subject.”
“The question in the scientific community is: What role does that particular biomarker play in terms of causing serious heart disease, stroke, and calcification of the aortic valve?”
“It’s pretty clear that, in and of itself, it actually can contribute and or cause any of those conditions,” he added. “The thing that’s then sort of problematic is that we don’t have a specific treatment to lower” Lp(a).
However, Dr. Wilson said that the statement underlines it is “still worth knowing” an individual’s Lp(a) concentrations because the risk with increased levels is “even higher for those people who have other conditions, such as metabolic disease or diabetes or high cholesterol.”
There are nevertheless several drugs in phase 2 and 3 clinical trials that appear to have the potential to significantly lower Lp(a) levels.
“I’m very excited,” said Dr. Wilson, noting that, so far, the drugs seem to be “quite safe,” and the currently available data suggest that they can “reduce Lp(a) levels by about 90%, which is huge.”
“That’s better than any drug we’ve got on the market.”
He cautioned, however, that it is going to take time after the drugs are approved to see the real benefits and risks once they start being used in very large populations, given that raised Lp(a) concentrations are present in about 20% of the world population.
The publication of the NLA statement coincides with a similar one from the European Atherosclerosis Society presented at the European Society of Cardiology Congress 2022 on Aug. 29, and published simultaneously in the European Heart Journal.
Coauthor of the EAS statement, Alberico L. Catapano, MD, PhD, professor of pharmacology at the University of Milan, and past president of the EAS, said that there are many areas in which the two statements are “in complete agreement.”
“However, the spirit of the documents is different,” he continued, chief among them being that the EAS statement focuses on the “global risk” of ASCVD and provides a risk calculator to help balance the risk increase with Lp(a) with that from other factors.
Another is that increased Lp(a) levels are recognized as being on a continuum in terms of their risk, such that there is no level at which raised concentrations can be deemed safe.
Dr. Wilson agreed with Dr. Capatano’s assessment, saying that the EAS statement takes current scientific observations “a step further,” in part by emphasizing that Lp(a) is “only one piece of the puzzle” for determining an individuals’ cardiovascular risk.
This will have huge implications for the conversations clinicians have with patients over shared decision-making, Dr. Wilson added.
Nevertheless, Dr. Catapano underlined to this news organization that “both documents are very important” in terms of the need to “raise awareness about a causal risk factor” for cardiovascular disease as well as that modifying Lp(a) concentrations “will probably reduce the risk.”
The statement from the NLA builds on the association’s prior Recommendations for the Patient-Centered Management of Dyslipidemia, published in two parts in 2014 and 2015, and comes to many of the same conclusions as the EAS statement.
It explains that apolipoprotein A, a component of Lp(a) attached to apolipoprotein B, has “unique” properties that promote the “initiation and progression of atherosclerosis and calcific valvular aortic stenosis, through endothelial dysfunction and proinflammatory responses, and pro-osteogenic effects promoting calcification.”
This, in turn, has the potential to cause myocardial infarction and ischemic stroke, the authors note.
This has been confirmed in meta-analyses of prospective, population-based studies showing a high risk for MI, coronary heart disease, and ischemic stroke with high Lp(a) levels, the statement adds.
Moreover, large genetic studies have confirmed that Lp(a) is a causal factor, independent of low-density lipoprotein cholesterol levels, for MI, ischemic stroke, valvular aortic stenosis, coronary artery stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause mortality.
Like the authors of the EAS statement, the NLA statement authors underline that the measurement of Lp(a) is “currently not standardized or harmonized,” and there is insufficient evidence on the utility of different cut-offs for risk based on age, gender, ethnicity, or the presence of comorbid conditions.
However, they do suggest that Lp(a) levels greater than 50 mg/dL (> 100 nmol/L) may be considered as a risk-enhancing factor favoring the initiation of statin therapy, although they note that the threshold could be threefold higher in African American individuals.
Despite these reservations, the authors say that Lp(a) testing “is reasonable” for refining the risk assessment of ASCVD in the first-degree relatives of people with premature ASCVD and those with a personal history of premature disease as well as in individuals with primary severe hypercholesterolemia.
Testing also “may be reasonable” to “aid in the clinician-patient discussion about whether to prescribe a statin” in people aged 40-75 years with borderline 10-year ASCVD risk, defined as 5%-7.4%, as well as in other equivocal clinical situations.
In terms of what to do in an individual with raised Lp(a) levels, the statement notes that lifestyle therapy and statins do not decrease Lp(a).
Although lomitapide (Juxtapid) and proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors both lower levels of the lipoprotein, the former is “not recommended for ASCVD risk reduction,” whereas the impact of the latter on ASCVD risk reduction via Lp(a) reduction “remains undetermined.”
Several experimental agents are currently under investigation to reduce Lp(a) levels, including SLN360 (Silence Therapeutics), and AKCEA-APO(a)-LRX (Akcea Therapeutics/Ionis Pharmaceuticals).
In the meantime, the authors say it is reasonable to use Lp(a) as a “risk-enhancing factor” for the initiation of moderate- or high-intensity statins in the primary prevention of ASCVD and to consider the addition of ezetimibe and/or PCSK9 inhibitors in high- and very high–risk patients already on maximally tolerated statin therapy.
Finally, the authors recognize the need for “additional evidence” to support clinical practice. In the absence of a randomized clinical trial of Lp(a) lowering in those who are at risk for ASCVD, they note that “several important unanswered questions remain.”
These include: “Is it reasonable to recommend universal testing of Lp(a) in everyone regardless of family history or health status at least once to help encourage healthy habits and inform clinical decision-making?” “Will earlier testing and effective interventions help to improve outcomes?”
Alongside more evidence in children, the authors also emphasize that “additional data are urgently needed in Blacks, South Asians, and those of Hispanic descent.”
No funding declared. Dr. Wilson declares relationships with Osler Institute, Merck Sharp & Dohm, Novo Nordisk, and Alexion Pharmaceuticals. Other authors also declare numerous relationships. Dr. Catapano declares a relationship with Novartis.
A version of this article first appeared on Medscape.com.