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Diltiazem fails to improve vasomotor dysfunction, angina in ANOCA: EDIT-CMD
In a randomized trial of patients with angina and no obstructive coronary artery disease (ANOCA), 6 weeks of treatment with diltiazem did not improve coronary vasomotor dysfunction – apart from epicardial spasm – or angina symptoms and quality of life.
The trial investigated whether this therapy would improve these outcomes in patients with two mutually exclusive subgroups, or endotypes, of coronary vasomotor dysfunction: coronary artery spasm (epicardial spasm, microvascular spasm) or coronary microvascular dysfunction indicated by coronary flow reserve (CFR) and index of microvascular resistance (IMR) values.
Treatment success, the primary study endpoint – defined as normalization of one of the abnormal endotypes and no normal endotype becoming abnormal – was similar after treatment with diltiazem, compared with placebo. Nor were there significant differences for secondary endpoints apart from improvements in epicardial spasm in the two groups.
Tijn Jansen, MD, presented these findings from the EDIT-CMD trial in a featured clinical research session at the annual scientific sessions of the American College of Cardiology. The study was simultaneously published online April 2, 2022, in JACC: Cardiovascular Imaging.
“This first study using repeated coronary function testing provides a platform for future research,” concluded Dr. Jansen, a PhD candidate in the department of cardiology, Radboud University, Nijmegen, the Netherlands.
“We were surprised indeed” that diltiazem did not meet its primary endpoint for successful treatment and did not reduce symptoms or improve quality of life, compared with placebo, unlike results of the CorMicA trial, he said in an interview.
“We did find a treatment success, however, of 21%, which was slightly lower than expected, but it was not better than just giving placebo. This was similar regarding symptoms and quality of life, where we did find an overall improvement with diltiazem, but again not higher than using placebo,” he added. “It seems that giving the diagnosis to these patients itself creates a reduction in symptoms,” that might be caused by a reduction in stress, Dr. Jansen suggested.
The clinical implication, he said, is that more randomized controlled trials in this patient population are needed to permit evidence-based patient-tailored treatment, based on the different endotypes. “It might even be imaginable to test effectiveness in each individual patient using coronary function testing,” he said.
These tests are more and more commonly used in clinical practice, Dr. Jansen noted. “In the Netherlands, we recently launched the NL-CFT registry, which enables the participating centers to perform the CFT with a standardized protocol, with the goal to collect data and increase knowledge in this patient population.”
Heterogeneous population?
“I think probably the reason this trial was negative is [that coronary vasomotor dysfunction is] just too heterogeneous,” assigned discussant, C. Noel Bairey Merz, MD, commented.
“The problem with effectiveness trials is that you get a very heterogeneous population, and not everything works for everyone,” she said.
“This was a strategy trial – too heterogenous and too small to assess each endotype response,” Dr. Bairey Merz elaborated in an interview.
“Calcium channel blockers [CCBs] will not [effectively] treat all endotypes of coronary microvascular dysfunction,” she added, noting that the 6-month CorMIcA trial demonstrated in a larger, more rigorous trial design that CCBs are effective for epicardial and microvascular spasm.
“If you were going to do this study again, would you allow physicians to do up-titration and/or go a little bit longer?” Dr. Bairey Merz asked Dr. Jansen during the discussion.
“I do think this is a very heterogeneous group,” he agreed. However, the protocol allowed researchers to titrate diltiazem from 120 mg/day to 360 mg/day.
“If I were to do it again,” Dr. Jansen said, “I would focus on one specific endotype, probably epicardial spasm.”
First RCT of diltiazem in patients with ANOCA
Up to 40% of patients undergoing coronary angiography for stable angina do not have obstructive coronary artery disease (CAD), and 60%-90% of these patients have coronary vasomotor dysfunction, Dr. Jansen noted.
The landmark CorMicA trial showed that diagnosing the specific endotype of coronary vasomotor dysfunction using coronary function testing allows for tailored medication that decreased angina and improved quality of life, the researchers noted.
A recent European Society of Cardiology position paper on ANOCA “recommends the use of various pharmacological treatments including calcium-channel blockers, beta-blockers, ACE inhibitors, statins, and nitric oxide modulators, of which CCBs have the most prominent role in both endotypes of coronary vasospasms” and coronary microvascular dysfunction, they wrote.
“However, evidence substantiating these recommendations is lacking,” the researchers added, “since it is based on studies in a different population, with small sample sizes, or not placebo controlled.”
To investigate this, between 2019 and 2021, EDIT-CMD enrolled 126 adults aged 18 years and older who had two or more chronic angina episodes per week and no signs of obstructive CAD, who were seen at three hospitals specializing in ANOCA in the Netherlands.
The participants underwent coronary function testing that consisted of an acetylcholine spasm provocation test to evaluate for epicardial spasm and microvascular spasm, and a bolus thermodilution test with adenosine, to assess CFR and IMR. Coronary microvascular dysfunction was defined as CFR less than 2.0 and IMR of 25 or greater.
Of 99 patients with vasospasm or microvascular dysfunction, 85 patients were randomly assigned to receive diltiazem (n = 41) or placebo (n = 44) for 6 weeks.
The patients in both groups had a mean age of 58 years, and 29% were male; 22% had previously undergone percutaneous coronary intervention, and 48% had severe angina (Canadian Cardiovascular Society grade III/IV).
At baseline, about 50% had epicardial spasm, 25% had microvascular spasm and 25% had no spasm, and 54% in the diltiazem group and 73% in the placebo group had microvascular dysfunction.
After 6 weeks, 73 patients (35 in the placebo group and 38 in the diltiazem group) were available for repeat coronary function testing.
For the primary outcome, after 6 weeks of treatment, the proportion of patients with normalization of one abnormal parameter of coronary vasomotor dysfunction, without any normal parameter becoming abnormal, occurred in 8 patients (21%) in the diltiazem group versus 10 patients (29%) in the placebo group (P = .46)
In secondary outcomes, after 6 weeks of treatment, there were no significant differences in the prevalence of microvascular dysfunction, in Seattle Angina Questionnaire scores for angina symptoms, or RAND-36 scores for quality of life between patients who received diltiazem vs those who received placebo.
However, more patients in the diltiazem group than in the placebo group progressed from epicardial spasm to microvascular or no spasm (47% vs. 6%; P = .006).
The EDIT-CMD trial was sponsored by Abbott. Dr. Jansen has no relevant financial disclosures. Dr. Bairey Merz discloses having a fiduciary role and shares in iRhythm and being on the advisory board for Sanofi.
A version of this article first appeared on Medscape.com.
In a randomized trial of patients with angina and no obstructive coronary artery disease (ANOCA), 6 weeks of treatment with diltiazem did not improve coronary vasomotor dysfunction – apart from epicardial spasm – or angina symptoms and quality of life.
The trial investigated whether this therapy would improve these outcomes in patients with two mutually exclusive subgroups, or endotypes, of coronary vasomotor dysfunction: coronary artery spasm (epicardial spasm, microvascular spasm) or coronary microvascular dysfunction indicated by coronary flow reserve (CFR) and index of microvascular resistance (IMR) values.
Treatment success, the primary study endpoint – defined as normalization of one of the abnormal endotypes and no normal endotype becoming abnormal – was similar after treatment with diltiazem, compared with placebo. Nor were there significant differences for secondary endpoints apart from improvements in epicardial spasm in the two groups.
Tijn Jansen, MD, presented these findings from the EDIT-CMD trial in a featured clinical research session at the annual scientific sessions of the American College of Cardiology. The study was simultaneously published online April 2, 2022, in JACC: Cardiovascular Imaging.
“This first study using repeated coronary function testing provides a platform for future research,” concluded Dr. Jansen, a PhD candidate in the department of cardiology, Radboud University, Nijmegen, the Netherlands.
“We were surprised indeed” that diltiazem did not meet its primary endpoint for successful treatment and did not reduce symptoms or improve quality of life, compared with placebo, unlike results of the CorMicA trial, he said in an interview.
“We did find a treatment success, however, of 21%, which was slightly lower than expected, but it was not better than just giving placebo. This was similar regarding symptoms and quality of life, where we did find an overall improvement with diltiazem, but again not higher than using placebo,” he added. “It seems that giving the diagnosis to these patients itself creates a reduction in symptoms,” that might be caused by a reduction in stress, Dr. Jansen suggested.
The clinical implication, he said, is that more randomized controlled trials in this patient population are needed to permit evidence-based patient-tailored treatment, based on the different endotypes. “It might even be imaginable to test effectiveness in each individual patient using coronary function testing,” he said.
These tests are more and more commonly used in clinical practice, Dr. Jansen noted. “In the Netherlands, we recently launched the NL-CFT registry, which enables the participating centers to perform the CFT with a standardized protocol, with the goal to collect data and increase knowledge in this patient population.”
Heterogeneous population?
“I think probably the reason this trial was negative is [that coronary vasomotor dysfunction is] just too heterogeneous,” assigned discussant, C. Noel Bairey Merz, MD, commented.
“The problem with effectiveness trials is that you get a very heterogeneous population, and not everything works for everyone,” she said.
“This was a strategy trial – too heterogenous and too small to assess each endotype response,” Dr. Bairey Merz elaborated in an interview.
“Calcium channel blockers [CCBs] will not [effectively] treat all endotypes of coronary microvascular dysfunction,” she added, noting that the 6-month CorMIcA trial demonstrated in a larger, more rigorous trial design that CCBs are effective for epicardial and microvascular spasm.
“If you were going to do this study again, would you allow physicians to do up-titration and/or go a little bit longer?” Dr. Bairey Merz asked Dr. Jansen during the discussion.
“I do think this is a very heterogeneous group,” he agreed. However, the protocol allowed researchers to titrate diltiazem from 120 mg/day to 360 mg/day.
“If I were to do it again,” Dr. Jansen said, “I would focus on one specific endotype, probably epicardial spasm.”
First RCT of diltiazem in patients with ANOCA
Up to 40% of patients undergoing coronary angiography for stable angina do not have obstructive coronary artery disease (CAD), and 60%-90% of these patients have coronary vasomotor dysfunction, Dr. Jansen noted.
The landmark CorMicA trial showed that diagnosing the specific endotype of coronary vasomotor dysfunction using coronary function testing allows for tailored medication that decreased angina and improved quality of life, the researchers noted.
A recent European Society of Cardiology position paper on ANOCA “recommends the use of various pharmacological treatments including calcium-channel blockers, beta-blockers, ACE inhibitors, statins, and nitric oxide modulators, of which CCBs have the most prominent role in both endotypes of coronary vasospasms” and coronary microvascular dysfunction, they wrote.
“However, evidence substantiating these recommendations is lacking,” the researchers added, “since it is based on studies in a different population, with small sample sizes, or not placebo controlled.”
To investigate this, between 2019 and 2021, EDIT-CMD enrolled 126 adults aged 18 years and older who had two or more chronic angina episodes per week and no signs of obstructive CAD, who were seen at three hospitals specializing in ANOCA in the Netherlands.
The participants underwent coronary function testing that consisted of an acetylcholine spasm provocation test to evaluate for epicardial spasm and microvascular spasm, and a bolus thermodilution test with adenosine, to assess CFR and IMR. Coronary microvascular dysfunction was defined as CFR less than 2.0 and IMR of 25 or greater.
Of 99 patients with vasospasm or microvascular dysfunction, 85 patients were randomly assigned to receive diltiazem (n = 41) or placebo (n = 44) for 6 weeks.
The patients in both groups had a mean age of 58 years, and 29% were male; 22% had previously undergone percutaneous coronary intervention, and 48% had severe angina (Canadian Cardiovascular Society grade III/IV).
At baseline, about 50% had epicardial spasm, 25% had microvascular spasm and 25% had no spasm, and 54% in the diltiazem group and 73% in the placebo group had microvascular dysfunction.
After 6 weeks, 73 patients (35 in the placebo group and 38 in the diltiazem group) were available for repeat coronary function testing.
For the primary outcome, after 6 weeks of treatment, the proportion of patients with normalization of one abnormal parameter of coronary vasomotor dysfunction, without any normal parameter becoming abnormal, occurred in 8 patients (21%) in the diltiazem group versus 10 patients (29%) in the placebo group (P = .46)
In secondary outcomes, after 6 weeks of treatment, there were no significant differences in the prevalence of microvascular dysfunction, in Seattle Angina Questionnaire scores for angina symptoms, or RAND-36 scores for quality of life between patients who received diltiazem vs those who received placebo.
However, more patients in the diltiazem group than in the placebo group progressed from epicardial spasm to microvascular or no spasm (47% vs. 6%; P = .006).
The EDIT-CMD trial was sponsored by Abbott. Dr. Jansen has no relevant financial disclosures. Dr. Bairey Merz discloses having a fiduciary role and shares in iRhythm and being on the advisory board for Sanofi.
A version of this article first appeared on Medscape.com.
In a randomized trial of patients with angina and no obstructive coronary artery disease (ANOCA), 6 weeks of treatment with diltiazem did not improve coronary vasomotor dysfunction – apart from epicardial spasm – or angina symptoms and quality of life.
The trial investigated whether this therapy would improve these outcomes in patients with two mutually exclusive subgroups, or endotypes, of coronary vasomotor dysfunction: coronary artery spasm (epicardial spasm, microvascular spasm) or coronary microvascular dysfunction indicated by coronary flow reserve (CFR) and index of microvascular resistance (IMR) values.
Treatment success, the primary study endpoint – defined as normalization of one of the abnormal endotypes and no normal endotype becoming abnormal – was similar after treatment with diltiazem, compared with placebo. Nor were there significant differences for secondary endpoints apart from improvements in epicardial spasm in the two groups.
Tijn Jansen, MD, presented these findings from the EDIT-CMD trial in a featured clinical research session at the annual scientific sessions of the American College of Cardiology. The study was simultaneously published online April 2, 2022, in JACC: Cardiovascular Imaging.
“This first study using repeated coronary function testing provides a platform for future research,” concluded Dr. Jansen, a PhD candidate in the department of cardiology, Radboud University, Nijmegen, the Netherlands.
“We were surprised indeed” that diltiazem did not meet its primary endpoint for successful treatment and did not reduce symptoms or improve quality of life, compared with placebo, unlike results of the CorMicA trial, he said in an interview.
“We did find a treatment success, however, of 21%, which was slightly lower than expected, but it was not better than just giving placebo. This was similar regarding symptoms and quality of life, where we did find an overall improvement with diltiazem, but again not higher than using placebo,” he added. “It seems that giving the diagnosis to these patients itself creates a reduction in symptoms,” that might be caused by a reduction in stress, Dr. Jansen suggested.
The clinical implication, he said, is that more randomized controlled trials in this patient population are needed to permit evidence-based patient-tailored treatment, based on the different endotypes. “It might even be imaginable to test effectiveness in each individual patient using coronary function testing,” he said.
These tests are more and more commonly used in clinical practice, Dr. Jansen noted. “In the Netherlands, we recently launched the NL-CFT registry, which enables the participating centers to perform the CFT with a standardized protocol, with the goal to collect data and increase knowledge in this patient population.”
Heterogeneous population?
“I think probably the reason this trial was negative is [that coronary vasomotor dysfunction is] just too heterogeneous,” assigned discussant, C. Noel Bairey Merz, MD, commented.
“The problem with effectiveness trials is that you get a very heterogeneous population, and not everything works for everyone,” she said.
“This was a strategy trial – too heterogenous and too small to assess each endotype response,” Dr. Bairey Merz elaborated in an interview.
“Calcium channel blockers [CCBs] will not [effectively] treat all endotypes of coronary microvascular dysfunction,” she added, noting that the 6-month CorMIcA trial demonstrated in a larger, more rigorous trial design that CCBs are effective for epicardial and microvascular spasm.
“If you were going to do this study again, would you allow physicians to do up-titration and/or go a little bit longer?” Dr. Bairey Merz asked Dr. Jansen during the discussion.
“I do think this is a very heterogeneous group,” he agreed. However, the protocol allowed researchers to titrate diltiazem from 120 mg/day to 360 mg/day.
“If I were to do it again,” Dr. Jansen said, “I would focus on one specific endotype, probably epicardial spasm.”
First RCT of diltiazem in patients with ANOCA
Up to 40% of patients undergoing coronary angiography for stable angina do not have obstructive coronary artery disease (CAD), and 60%-90% of these patients have coronary vasomotor dysfunction, Dr. Jansen noted.
The landmark CorMicA trial showed that diagnosing the specific endotype of coronary vasomotor dysfunction using coronary function testing allows for tailored medication that decreased angina and improved quality of life, the researchers noted.
A recent European Society of Cardiology position paper on ANOCA “recommends the use of various pharmacological treatments including calcium-channel blockers, beta-blockers, ACE inhibitors, statins, and nitric oxide modulators, of which CCBs have the most prominent role in both endotypes of coronary vasospasms” and coronary microvascular dysfunction, they wrote.
“However, evidence substantiating these recommendations is lacking,” the researchers added, “since it is based on studies in a different population, with small sample sizes, or not placebo controlled.”
To investigate this, between 2019 and 2021, EDIT-CMD enrolled 126 adults aged 18 years and older who had two or more chronic angina episodes per week and no signs of obstructive CAD, who were seen at three hospitals specializing in ANOCA in the Netherlands.
The participants underwent coronary function testing that consisted of an acetylcholine spasm provocation test to evaluate for epicardial spasm and microvascular spasm, and a bolus thermodilution test with adenosine, to assess CFR and IMR. Coronary microvascular dysfunction was defined as CFR less than 2.0 and IMR of 25 or greater.
Of 99 patients with vasospasm or microvascular dysfunction, 85 patients were randomly assigned to receive diltiazem (n = 41) or placebo (n = 44) for 6 weeks.
The patients in both groups had a mean age of 58 years, and 29% were male; 22% had previously undergone percutaneous coronary intervention, and 48% had severe angina (Canadian Cardiovascular Society grade III/IV).
At baseline, about 50% had epicardial spasm, 25% had microvascular spasm and 25% had no spasm, and 54% in the diltiazem group and 73% in the placebo group had microvascular dysfunction.
After 6 weeks, 73 patients (35 in the placebo group and 38 in the diltiazem group) were available for repeat coronary function testing.
For the primary outcome, after 6 weeks of treatment, the proportion of patients with normalization of one abnormal parameter of coronary vasomotor dysfunction, without any normal parameter becoming abnormal, occurred in 8 patients (21%) in the diltiazem group versus 10 patients (29%) in the placebo group (P = .46)
In secondary outcomes, after 6 weeks of treatment, there were no significant differences in the prevalence of microvascular dysfunction, in Seattle Angina Questionnaire scores for angina symptoms, or RAND-36 scores for quality of life between patients who received diltiazem vs those who received placebo.
However, more patients in the diltiazem group than in the placebo group progressed from epicardial spasm to microvascular or no spasm (47% vs. 6%; P = .006).
The EDIT-CMD trial was sponsored by Abbott. Dr. Jansen has no relevant financial disclosures. Dr. Bairey Merz discloses having a fiduciary role and shares in iRhythm and being on the advisory board for Sanofi.
A version of this article first appeared on Medscape.com.
FROM ACC 2022
SCORED: Sotagliflozin shows robust MACE benefit
WASHINGTON – Results from new analyses further fleshed out the potent effect by the investigational SGLT1&2 inhibitor sotagliflozin on major cardiovascular adverse events in patients with type 2 diabetes, chronic kidney disease, and at high risk for cardiovascular disease in the SCORED trial that randomized more than 10,000 patients.
In prespecified, secondary analyses of the SCORED results, treatment with sotagliflozin during a median of 16 months was linked to a significant 21% risk reduction relative to placebo for the combined incidence of total major adverse cardiovascular events (MACE), which included cardiovascular death, first and recurrent episodes of nonfatal MI, and nonfatal stroke among the 5,144 randomized patients who entered the trial with a history of cardiovascular disease (CVD), Deepak L. Bhatt, MD, said at the annual scientific sessions of the American College of Cardiology.
Among the 5,440 patients in the study who did not have a history of CVD (although they did have at least one major risk factor or at least two minor risk factors), treatment with sotagliflozin was linked to a significant 26% relative risk reduction in total MACE events.
Part of these overall MACE benefits resulted from similar improvements from sotagliflozin treatment on the individual outcomes of total nonfatal MI and total nonfatal strokes. Treatment with sotagliflozin cut these MIs by a significant 31% in patients with a history of CVD relative to patients who received placebo, and by a relative 34% in those without a CVD event in their history, a difference compared with placebo that fell short of significance, said Dr. Bhatt, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Health, both in Boston.
Treatment with sotagliflozin also cut total nonfatal strokes by 31% relative to placebo in patients with a history of CVD, and by a relative 38% in those without a CVD history. Both differences fell short of significance.
An early MACE benefit and a stroke benefit
“This stroke benefit has not been clearly seen” with any agent from the closely related sodium-glucose cotransport-2 (SGLT2) inhibitor class, and “the MACE benefit appeared very early,” within 3 months from the start of sotagliflozin treatment, “which may be because of the SGLT1 inhibition,” Dr. Bhatt said during his report.
The SGLT1 receptor is the primary mechanism cells in the gut use to absorb glucose and galactose in the human gastrointestinal tract, Dr. Bhatt explained, while the SGLT2 receptor appears on kidney cells and is the major player in the reabsorption of filtered glucose. The SGLT2 inhibitor class includes the agents canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), while sotagliflozin inhibits both SGLT1 and SGLT2.
Main results from SCORED appeared in a report first released in late 2020, and showed that for the study’s primary endpoint treatment with sotagliflozin linked with a significant 26% relative risk reduction for the composite of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure (N Engl J Med. 2021 Jan 14;384[2]:129-39). Patient follow-up in SCORED was not as long as originally planned when the study stopped early due to a loss of funding from a sponsor that was triggered by the COVID-19 pandemic.
MACE results ‘heterogeneous’ from SGLT2 inhibitors
Sotagliflozin and agents from the SGLT2 inhibitor class “have been consistent” in their benefits for reducing cardiovascular death and hospitalization for heart failure, but for MACE, the results from the SGLT2 inhibitors “have been more heterogeneous,” and the effect of sotagliflozin on MACE “were different in SCORED,” commented Michelle L. O’Donoghue, MD, MPH, a cardiologist at Brigham and Women’s Hospital in Boston who was not involved with this work.
“The results suggest a benefit [from sotagliflozin] on atherosclerotic events, which could be a potential advantage” compared with the SGLT2 inhibitors, “but the heterogeneity of this effect” among these agents means that more confirmatory data are needed for sotagliflozin, Dr. O’Donoghue said in an interview.
“There is a lot of enthusiasm for the concept” of combined inhibition of the SGLT1 and 2 receptors, and if more evidence for unique benefits of this effect accumulate “it may lead to increased enthusiasm for sotagliflozin,” she said. “A lot will also depend on pricing decisions” for sotagliflozin, if it receives U.S. marketing approval from the Food and Drug Administration. Decisions about which agent from the SGLT2 inhibitor class to prescribe “are often being made based on price right now,” Dr. O’Donoghue said.
Lexicon Pharmaceuticals, the company developing sotagliflozin, has announced plans to resubmit its new drug application for sotagliflozin to the FDA later in 2022, with the agency’s approval decision likely occurring late in 2022 or sometime during 2023. In February, the company withdrew its December 2021 application to correct a “technical issue” it had found.
An additional analysis reported by Dr. Bhatt used combined data from SCORED as well as several additional randomized trials of sotagliflozin involving a total of more than 20,000 patients that showed a significant 21% reduction in the incidence of MACE compared with placebo.
During his talk, Dr. Bhatt said that sotagliflozin was potentially superior to the agents that inhibit only SGLT2. In an interview, he based this tentative assessment on at least four attributes of sotagliflozin that have emerged from trial results:
- The drug’s ability to significantly reduce MACE and to have this effect apparent within a few months of treatment onset;
- The significantly reduced rate of stroke with sotagliflozin (when patients are not subdivided into those with or without a history of CVD) that has not yet been seen with any SGLT2 inhibitor;
- The ability of sotagliflozin to reduce hemoglobin A1c levels in patients with type 2 diabetes even when their estimated glomerular filtration rate is less than 30 mL/min per 1.73 m2, an effect not seen with SGLT2 inhibitors and possibly explained by sotagliflozin having an effect on gut absorption of glucose in addition to its SGLT2 inhibitory effect in the kidney;
- And the proven ability of sotagliflozin to be safe and effective when initiated in patients hospitalized for heart failure, a property that so far has only also been shown for the SGLT2 inhibitor empagliflozin in the EMPULSE trial (Nature Med. 2022 Mar;28: 568-74).
SCORED was sponsored by Sanofi and Lexicon Pharmaceuticals, the companies originally developing sotagliflozin, although with the withdrawal of Sanofi’s support, further development is now sponsored entirely by Lexicon. Dr. Bhatt received research funding from Sanofi and Lexicon that was paid to Brigham and Women’s Health, and he has been an advisor to numerous companies. Dr. O’Donoghue has been a consultant to Amgen, Janssen, and Novartis, and has received research funding from Amgen, AZ MedImmune, Intarcia, Janssen, Merck, and Novartis.
WASHINGTON – Results from new analyses further fleshed out the potent effect by the investigational SGLT1&2 inhibitor sotagliflozin on major cardiovascular adverse events in patients with type 2 diabetes, chronic kidney disease, and at high risk for cardiovascular disease in the SCORED trial that randomized more than 10,000 patients.
In prespecified, secondary analyses of the SCORED results, treatment with sotagliflozin during a median of 16 months was linked to a significant 21% risk reduction relative to placebo for the combined incidence of total major adverse cardiovascular events (MACE), which included cardiovascular death, first and recurrent episodes of nonfatal MI, and nonfatal stroke among the 5,144 randomized patients who entered the trial with a history of cardiovascular disease (CVD), Deepak L. Bhatt, MD, said at the annual scientific sessions of the American College of Cardiology.
Among the 5,440 patients in the study who did not have a history of CVD (although they did have at least one major risk factor or at least two minor risk factors), treatment with sotagliflozin was linked to a significant 26% relative risk reduction in total MACE events.
Part of these overall MACE benefits resulted from similar improvements from sotagliflozin treatment on the individual outcomes of total nonfatal MI and total nonfatal strokes. Treatment with sotagliflozin cut these MIs by a significant 31% in patients with a history of CVD relative to patients who received placebo, and by a relative 34% in those without a CVD event in their history, a difference compared with placebo that fell short of significance, said Dr. Bhatt, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Health, both in Boston.
Treatment with sotagliflozin also cut total nonfatal strokes by 31% relative to placebo in patients with a history of CVD, and by a relative 38% in those without a CVD history. Both differences fell short of significance.
An early MACE benefit and a stroke benefit
“This stroke benefit has not been clearly seen” with any agent from the closely related sodium-glucose cotransport-2 (SGLT2) inhibitor class, and “the MACE benefit appeared very early,” within 3 months from the start of sotagliflozin treatment, “which may be because of the SGLT1 inhibition,” Dr. Bhatt said during his report.
The SGLT1 receptor is the primary mechanism cells in the gut use to absorb glucose and galactose in the human gastrointestinal tract, Dr. Bhatt explained, while the SGLT2 receptor appears on kidney cells and is the major player in the reabsorption of filtered glucose. The SGLT2 inhibitor class includes the agents canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), while sotagliflozin inhibits both SGLT1 and SGLT2.
Main results from SCORED appeared in a report first released in late 2020, and showed that for the study’s primary endpoint treatment with sotagliflozin linked with a significant 26% relative risk reduction for the composite of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure (N Engl J Med. 2021 Jan 14;384[2]:129-39). Patient follow-up in SCORED was not as long as originally planned when the study stopped early due to a loss of funding from a sponsor that was triggered by the COVID-19 pandemic.
MACE results ‘heterogeneous’ from SGLT2 inhibitors
Sotagliflozin and agents from the SGLT2 inhibitor class “have been consistent” in their benefits for reducing cardiovascular death and hospitalization for heart failure, but for MACE, the results from the SGLT2 inhibitors “have been more heterogeneous,” and the effect of sotagliflozin on MACE “were different in SCORED,” commented Michelle L. O’Donoghue, MD, MPH, a cardiologist at Brigham and Women’s Hospital in Boston who was not involved with this work.
“The results suggest a benefit [from sotagliflozin] on atherosclerotic events, which could be a potential advantage” compared with the SGLT2 inhibitors, “but the heterogeneity of this effect” among these agents means that more confirmatory data are needed for sotagliflozin, Dr. O’Donoghue said in an interview.
“There is a lot of enthusiasm for the concept” of combined inhibition of the SGLT1 and 2 receptors, and if more evidence for unique benefits of this effect accumulate “it may lead to increased enthusiasm for sotagliflozin,” she said. “A lot will also depend on pricing decisions” for sotagliflozin, if it receives U.S. marketing approval from the Food and Drug Administration. Decisions about which agent from the SGLT2 inhibitor class to prescribe “are often being made based on price right now,” Dr. O’Donoghue said.
Lexicon Pharmaceuticals, the company developing sotagliflozin, has announced plans to resubmit its new drug application for sotagliflozin to the FDA later in 2022, with the agency’s approval decision likely occurring late in 2022 or sometime during 2023. In February, the company withdrew its December 2021 application to correct a “technical issue” it had found.
An additional analysis reported by Dr. Bhatt used combined data from SCORED as well as several additional randomized trials of sotagliflozin involving a total of more than 20,000 patients that showed a significant 21% reduction in the incidence of MACE compared with placebo.
During his talk, Dr. Bhatt said that sotagliflozin was potentially superior to the agents that inhibit only SGLT2. In an interview, he based this tentative assessment on at least four attributes of sotagliflozin that have emerged from trial results:
- The drug’s ability to significantly reduce MACE and to have this effect apparent within a few months of treatment onset;
- The significantly reduced rate of stroke with sotagliflozin (when patients are not subdivided into those with or without a history of CVD) that has not yet been seen with any SGLT2 inhibitor;
- The ability of sotagliflozin to reduce hemoglobin A1c levels in patients with type 2 diabetes even when their estimated glomerular filtration rate is less than 30 mL/min per 1.73 m2, an effect not seen with SGLT2 inhibitors and possibly explained by sotagliflozin having an effect on gut absorption of glucose in addition to its SGLT2 inhibitory effect in the kidney;
- And the proven ability of sotagliflozin to be safe and effective when initiated in patients hospitalized for heart failure, a property that so far has only also been shown for the SGLT2 inhibitor empagliflozin in the EMPULSE trial (Nature Med. 2022 Mar;28: 568-74).
SCORED was sponsored by Sanofi and Lexicon Pharmaceuticals, the companies originally developing sotagliflozin, although with the withdrawal of Sanofi’s support, further development is now sponsored entirely by Lexicon. Dr. Bhatt received research funding from Sanofi and Lexicon that was paid to Brigham and Women’s Health, and he has been an advisor to numerous companies. Dr. O’Donoghue has been a consultant to Amgen, Janssen, and Novartis, and has received research funding from Amgen, AZ MedImmune, Intarcia, Janssen, Merck, and Novartis.
WASHINGTON – Results from new analyses further fleshed out the potent effect by the investigational SGLT1&2 inhibitor sotagliflozin on major cardiovascular adverse events in patients with type 2 diabetes, chronic kidney disease, and at high risk for cardiovascular disease in the SCORED trial that randomized more than 10,000 patients.
In prespecified, secondary analyses of the SCORED results, treatment with sotagliflozin during a median of 16 months was linked to a significant 21% risk reduction relative to placebo for the combined incidence of total major adverse cardiovascular events (MACE), which included cardiovascular death, first and recurrent episodes of nonfatal MI, and nonfatal stroke among the 5,144 randomized patients who entered the trial with a history of cardiovascular disease (CVD), Deepak L. Bhatt, MD, said at the annual scientific sessions of the American College of Cardiology.
Among the 5,440 patients in the study who did not have a history of CVD (although they did have at least one major risk factor or at least two minor risk factors), treatment with sotagliflozin was linked to a significant 26% relative risk reduction in total MACE events.
Part of these overall MACE benefits resulted from similar improvements from sotagliflozin treatment on the individual outcomes of total nonfatal MI and total nonfatal strokes. Treatment with sotagliflozin cut these MIs by a significant 31% in patients with a history of CVD relative to patients who received placebo, and by a relative 34% in those without a CVD event in their history, a difference compared with placebo that fell short of significance, said Dr. Bhatt, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Health, both in Boston.
Treatment with sotagliflozin also cut total nonfatal strokes by 31% relative to placebo in patients with a history of CVD, and by a relative 38% in those without a CVD history. Both differences fell short of significance.
An early MACE benefit and a stroke benefit
“This stroke benefit has not been clearly seen” with any agent from the closely related sodium-glucose cotransport-2 (SGLT2) inhibitor class, and “the MACE benefit appeared very early,” within 3 months from the start of sotagliflozin treatment, “which may be because of the SGLT1 inhibition,” Dr. Bhatt said during his report.
The SGLT1 receptor is the primary mechanism cells in the gut use to absorb glucose and galactose in the human gastrointestinal tract, Dr. Bhatt explained, while the SGLT2 receptor appears on kidney cells and is the major player in the reabsorption of filtered glucose. The SGLT2 inhibitor class includes the agents canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), while sotagliflozin inhibits both SGLT1 and SGLT2.
Main results from SCORED appeared in a report first released in late 2020, and showed that for the study’s primary endpoint treatment with sotagliflozin linked with a significant 26% relative risk reduction for the composite of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure (N Engl J Med. 2021 Jan 14;384[2]:129-39). Patient follow-up in SCORED was not as long as originally planned when the study stopped early due to a loss of funding from a sponsor that was triggered by the COVID-19 pandemic.
MACE results ‘heterogeneous’ from SGLT2 inhibitors
Sotagliflozin and agents from the SGLT2 inhibitor class “have been consistent” in their benefits for reducing cardiovascular death and hospitalization for heart failure, but for MACE, the results from the SGLT2 inhibitors “have been more heterogeneous,” and the effect of sotagliflozin on MACE “were different in SCORED,” commented Michelle L. O’Donoghue, MD, MPH, a cardiologist at Brigham and Women’s Hospital in Boston who was not involved with this work.
“The results suggest a benefit [from sotagliflozin] on atherosclerotic events, which could be a potential advantage” compared with the SGLT2 inhibitors, “but the heterogeneity of this effect” among these agents means that more confirmatory data are needed for sotagliflozin, Dr. O’Donoghue said in an interview.
“There is a lot of enthusiasm for the concept” of combined inhibition of the SGLT1 and 2 receptors, and if more evidence for unique benefits of this effect accumulate “it may lead to increased enthusiasm for sotagliflozin,” she said. “A lot will also depend on pricing decisions” for sotagliflozin, if it receives U.S. marketing approval from the Food and Drug Administration. Decisions about which agent from the SGLT2 inhibitor class to prescribe “are often being made based on price right now,” Dr. O’Donoghue said.
Lexicon Pharmaceuticals, the company developing sotagliflozin, has announced plans to resubmit its new drug application for sotagliflozin to the FDA later in 2022, with the agency’s approval decision likely occurring late in 2022 or sometime during 2023. In February, the company withdrew its December 2021 application to correct a “technical issue” it had found.
An additional analysis reported by Dr. Bhatt used combined data from SCORED as well as several additional randomized trials of sotagliflozin involving a total of more than 20,000 patients that showed a significant 21% reduction in the incidence of MACE compared with placebo.
During his talk, Dr. Bhatt said that sotagliflozin was potentially superior to the agents that inhibit only SGLT2. In an interview, he based this tentative assessment on at least four attributes of sotagliflozin that have emerged from trial results:
- The drug’s ability to significantly reduce MACE and to have this effect apparent within a few months of treatment onset;
- The significantly reduced rate of stroke with sotagliflozin (when patients are not subdivided into those with or without a history of CVD) that has not yet been seen with any SGLT2 inhibitor;
- The ability of sotagliflozin to reduce hemoglobin A1c levels in patients with type 2 diabetes even when their estimated glomerular filtration rate is less than 30 mL/min per 1.73 m2, an effect not seen with SGLT2 inhibitors and possibly explained by sotagliflozin having an effect on gut absorption of glucose in addition to its SGLT2 inhibitory effect in the kidney;
- And the proven ability of sotagliflozin to be safe and effective when initiated in patients hospitalized for heart failure, a property that so far has only also been shown for the SGLT2 inhibitor empagliflozin in the EMPULSE trial (Nature Med. 2022 Mar;28: 568-74).
SCORED was sponsored by Sanofi and Lexicon Pharmaceuticals, the companies originally developing sotagliflozin, although with the withdrawal of Sanofi’s support, further development is now sponsored entirely by Lexicon. Dr. Bhatt received research funding from Sanofi and Lexicon that was paid to Brigham and Women’s Health, and he has been an advisor to numerous companies. Dr. O’Donoghue has been a consultant to Amgen, Janssen, and Novartis, and has received research funding from Amgen, AZ MedImmune, Intarcia, Janssen, Merck, and Novartis.
AT ACC 2022
Avocados linked to lower cardiovascular risk
A prospective study that followed more than 110,000 men and women for more than 30 years suggests that .
Researchers also found that replacing half a serving of butter, cheese, bacon, or other animal product with an equivalent amount of avocado was associated with up to 22% lower risk for CVD events.
The findings add to evidence from other studies that has shown that avocados – which contain multiple nutrients, including fiber and unsaturated, healthy fats – have a positive impact on cardiovascular risk factors, first author Lorena S. Pacheco, PhD, a postdoctoral research fellow at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.
“This research complements and expands on the current literature that we have on unsaturated fats and reduced risk of cardiovascular disease and also underscores how bad saturated fats, like butter, cheese, and processed meats are for the heart,” Dr. Pacheco said.
“For the most part, we have known that avocados are healthy, but I think this study, because of its numbers and duration, adds a little more substance to that knowledge now,” Dr. Pacheco said.
The findings were published online March 30 in the Journal of the American Heart Association.
Avocados are dense with nutrients. They are high in fat, but in monounsaturated fats (MUFAs) and polyunsaturated fats (PUFAs), which are viewed as good.
A medium-sized (136 g) Haas avocado, which is the most commonly consumed avocado in the United States, contains roughly 13 g of oleic acid. Avocados also contain dietary fiber, potassium, magnesium, phytonutrients, and bioactive compounds.
To see the effect avocados can have on cardiovascular health, Dr. Pacheco and her team turned to two large, long-running cohort studies: the Nurses’ Health Study (NHS), which began in the early 1970s with 68,786 women 30-55 years of age; and the Health Professionals Follow-up Study (HPFS), which ran from 1986 to 2016 and followed 41,701 men 40-75 years of age.
All were free of cancer, coronary heart disease, and stroke at study entry.
Participants completed a validated food frequency questionnaire at baseline and every 4 years thereafter. The questionnaire asked about the amount and frequency of avocado consumed. One serving equaled half an avocado, or half a cup.
In the early days of the NHS, very few participants said they ate avocados, but that began to change over the years, as the popularity of avocados grew.
“The NHS cohort was recruited back in the late ‘70s, and the health professionals cohort did not start until the mid 1980s, when avocado consumption was really low,” Dr. Pacheco said.
“What is beautiful about these cohorts is we are able to ask participants questions and then save the answers that they give us throughout the years to answer questions that might arise whenever the question is right. So it just depends on when you accrue enough data to ask those questions about potential cardiovascular benefit with avocados,” she said.
There were 9,185 coronary heart disease events and 5,290 strokes documented over 30 years of follow-up.
After adjustment for lifestyle and other dietary factors, those with a higher avocado intake – at least two servings per week – had a 16% lower risk for CVD (pooled hazard ratio, 0.84; 95% CI, 0.75-0.95) and a 21% lower risk for coronary heart disease (pooled HR, 0.79; 95% CI, 0.68-0.91).
No significant associations were seen for stroke, but this is because the study did not have sufficient numbers, Dr. Pacheco explained.
A statistical model also determined that replacing half a serving daily of margarine, butter, egg, yogurt, cheese, or processed meats, such as bacon, with the same amount of avocado was associated with a 16%-22% lower risk for CVD events.
“I want to emphasize that the study is an epidemiological observational study and cannot prove cause and effect,” Dr. Pacheco said.
“It’s not a clinical trial – it’s based on observational epidemiology – but we saw patterns in the model: Avocado consumption and substituting avocado for other unhealthy fats reduced the risk of having a cardiovascular event or coronary heart disease,” she said.
The findings are significant “because a healthy dietary pattern is the cornerstone for cardiovascular health; however, it can be difficult for many Americans to achieve and adhere to healthy eating patterns,” Cheryl Anderson, PhD, professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, who is chair of the AHA’s Council on Epidemiology and Prevention, said in a statement.
“We desperately need strategies to improve intake of AHA-recommended healthy diets, such as the Mediterranean diet, that are rich in vegetables and fruits. Although no one food is the solution to routinely eating a healthy diet, this study is evidence that avocados have possible health benefits. This is promising because it is a food item that is popular, accessible, desirable, and easy to include in meals eaten by many Americans at home and in restaurants,” said Dr. Anderson, who was not part of the study.
Dr. Pacheco and Dr. Anderson report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A prospective study that followed more than 110,000 men and women for more than 30 years suggests that .
Researchers also found that replacing half a serving of butter, cheese, bacon, or other animal product with an equivalent amount of avocado was associated with up to 22% lower risk for CVD events.
The findings add to evidence from other studies that has shown that avocados – which contain multiple nutrients, including fiber and unsaturated, healthy fats – have a positive impact on cardiovascular risk factors, first author Lorena S. Pacheco, PhD, a postdoctoral research fellow at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.
“This research complements and expands on the current literature that we have on unsaturated fats and reduced risk of cardiovascular disease and also underscores how bad saturated fats, like butter, cheese, and processed meats are for the heart,” Dr. Pacheco said.
“For the most part, we have known that avocados are healthy, but I think this study, because of its numbers and duration, adds a little more substance to that knowledge now,” Dr. Pacheco said.
The findings were published online March 30 in the Journal of the American Heart Association.
Avocados are dense with nutrients. They are high in fat, but in monounsaturated fats (MUFAs) and polyunsaturated fats (PUFAs), which are viewed as good.
A medium-sized (136 g) Haas avocado, which is the most commonly consumed avocado in the United States, contains roughly 13 g of oleic acid. Avocados also contain dietary fiber, potassium, magnesium, phytonutrients, and bioactive compounds.
To see the effect avocados can have on cardiovascular health, Dr. Pacheco and her team turned to two large, long-running cohort studies: the Nurses’ Health Study (NHS), which began in the early 1970s with 68,786 women 30-55 years of age; and the Health Professionals Follow-up Study (HPFS), which ran from 1986 to 2016 and followed 41,701 men 40-75 years of age.
All were free of cancer, coronary heart disease, and stroke at study entry.
Participants completed a validated food frequency questionnaire at baseline and every 4 years thereafter. The questionnaire asked about the amount and frequency of avocado consumed. One serving equaled half an avocado, or half a cup.
In the early days of the NHS, very few participants said they ate avocados, but that began to change over the years, as the popularity of avocados grew.
“The NHS cohort was recruited back in the late ‘70s, and the health professionals cohort did not start until the mid 1980s, when avocado consumption was really low,” Dr. Pacheco said.
“What is beautiful about these cohorts is we are able to ask participants questions and then save the answers that they give us throughout the years to answer questions that might arise whenever the question is right. So it just depends on when you accrue enough data to ask those questions about potential cardiovascular benefit with avocados,” she said.
There were 9,185 coronary heart disease events and 5,290 strokes documented over 30 years of follow-up.
After adjustment for lifestyle and other dietary factors, those with a higher avocado intake – at least two servings per week – had a 16% lower risk for CVD (pooled hazard ratio, 0.84; 95% CI, 0.75-0.95) and a 21% lower risk for coronary heart disease (pooled HR, 0.79; 95% CI, 0.68-0.91).
No significant associations were seen for stroke, but this is because the study did not have sufficient numbers, Dr. Pacheco explained.
A statistical model also determined that replacing half a serving daily of margarine, butter, egg, yogurt, cheese, or processed meats, such as bacon, with the same amount of avocado was associated with a 16%-22% lower risk for CVD events.
“I want to emphasize that the study is an epidemiological observational study and cannot prove cause and effect,” Dr. Pacheco said.
“It’s not a clinical trial – it’s based on observational epidemiology – but we saw patterns in the model: Avocado consumption and substituting avocado for other unhealthy fats reduced the risk of having a cardiovascular event or coronary heart disease,” she said.
The findings are significant “because a healthy dietary pattern is the cornerstone for cardiovascular health; however, it can be difficult for many Americans to achieve and adhere to healthy eating patterns,” Cheryl Anderson, PhD, professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, who is chair of the AHA’s Council on Epidemiology and Prevention, said in a statement.
“We desperately need strategies to improve intake of AHA-recommended healthy diets, such as the Mediterranean diet, that are rich in vegetables and fruits. Although no one food is the solution to routinely eating a healthy diet, this study is evidence that avocados have possible health benefits. This is promising because it is a food item that is popular, accessible, desirable, and easy to include in meals eaten by many Americans at home and in restaurants,” said Dr. Anderson, who was not part of the study.
Dr. Pacheco and Dr. Anderson report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A prospective study that followed more than 110,000 men and women for more than 30 years suggests that .
Researchers also found that replacing half a serving of butter, cheese, bacon, or other animal product with an equivalent amount of avocado was associated with up to 22% lower risk for CVD events.
The findings add to evidence from other studies that has shown that avocados – which contain multiple nutrients, including fiber and unsaturated, healthy fats – have a positive impact on cardiovascular risk factors, first author Lorena S. Pacheco, PhD, a postdoctoral research fellow at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.
“This research complements and expands on the current literature that we have on unsaturated fats and reduced risk of cardiovascular disease and also underscores how bad saturated fats, like butter, cheese, and processed meats are for the heart,” Dr. Pacheco said.
“For the most part, we have known that avocados are healthy, but I think this study, because of its numbers and duration, adds a little more substance to that knowledge now,” Dr. Pacheco said.
The findings were published online March 30 in the Journal of the American Heart Association.
Avocados are dense with nutrients. They are high in fat, but in monounsaturated fats (MUFAs) and polyunsaturated fats (PUFAs), which are viewed as good.
A medium-sized (136 g) Haas avocado, which is the most commonly consumed avocado in the United States, contains roughly 13 g of oleic acid. Avocados also contain dietary fiber, potassium, magnesium, phytonutrients, and bioactive compounds.
To see the effect avocados can have on cardiovascular health, Dr. Pacheco and her team turned to two large, long-running cohort studies: the Nurses’ Health Study (NHS), which began in the early 1970s with 68,786 women 30-55 years of age; and the Health Professionals Follow-up Study (HPFS), which ran from 1986 to 2016 and followed 41,701 men 40-75 years of age.
All were free of cancer, coronary heart disease, and stroke at study entry.
Participants completed a validated food frequency questionnaire at baseline and every 4 years thereafter. The questionnaire asked about the amount and frequency of avocado consumed. One serving equaled half an avocado, or half a cup.
In the early days of the NHS, very few participants said they ate avocados, but that began to change over the years, as the popularity of avocados grew.
“The NHS cohort was recruited back in the late ‘70s, and the health professionals cohort did not start until the mid 1980s, when avocado consumption was really low,” Dr. Pacheco said.
“What is beautiful about these cohorts is we are able to ask participants questions and then save the answers that they give us throughout the years to answer questions that might arise whenever the question is right. So it just depends on when you accrue enough data to ask those questions about potential cardiovascular benefit with avocados,” she said.
There were 9,185 coronary heart disease events and 5,290 strokes documented over 30 years of follow-up.
After adjustment for lifestyle and other dietary factors, those with a higher avocado intake – at least two servings per week – had a 16% lower risk for CVD (pooled hazard ratio, 0.84; 95% CI, 0.75-0.95) and a 21% lower risk for coronary heart disease (pooled HR, 0.79; 95% CI, 0.68-0.91).
No significant associations were seen for stroke, but this is because the study did not have sufficient numbers, Dr. Pacheco explained.
A statistical model also determined that replacing half a serving daily of margarine, butter, egg, yogurt, cheese, or processed meats, such as bacon, with the same amount of avocado was associated with a 16%-22% lower risk for CVD events.
“I want to emphasize that the study is an epidemiological observational study and cannot prove cause and effect,” Dr. Pacheco said.
“It’s not a clinical trial – it’s based on observational epidemiology – but we saw patterns in the model: Avocado consumption and substituting avocado for other unhealthy fats reduced the risk of having a cardiovascular event or coronary heart disease,” she said.
The findings are significant “because a healthy dietary pattern is the cornerstone for cardiovascular health; however, it can be difficult for many Americans to achieve and adhere to healthy eating patterns,” Cheryl Anderson, PhD, professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, who is chair of the AHA’s Council on Epidemiology and Prevention, said in a statement.
“We desperately need strategies to improve intake of AHA-recommended healthy diets, such as the Mediterranean diet, that are rich in vegetables and fruits. Although no one food is the solution to routinely eating a healthy diet, this study is evidence that avocados have possible health benefits. This is promising because it is a food item that is popular, accessible, desirable, and easy to include in meals eaten by many Americans at home and in restaurants,” said Dr. Anderson, who was not part of the study.
Dr. Pacheco and Dr. Anderson report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Calcium scores predict sudden-death risk in preclinical CAD
The risk for sudden cardiac death (SCD) climbs steadily in tandem with coronary artery calcium (CAC) burden, independent of more conventional risk factors, in primary-prevention patients considered low- to intermediate-risk, researchers say.
The findings, based on a large cohort study, strengthen the case for initial CAC imaging as a gatekeeper to further testing in such patients who have mostly subclinical atherosclerotic cardiovascular disease (ASCVD), they conclude.
The CAC scan is “evolving into a primary-prevention screening test, not only for initiating statin therapy, but now as a screening modality for risk stratifying someone for sudden cardiac arrest,” Alexander C. Razavi, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization.
“Our data reinforce this and give some quantitative measures of when we should start to consider that.”
A CAC score of 100 to 399 in this “primarily asymptomatic,” predominantly White and male cohort elevated the risk for SCD over an average of 10.6 years by a factor of 2.8, compared with a score of 0. The risk went up four times with CAC scores of 400-999, and almost five times with scores above 1,000.
The risk association was independent of age and sex but also diabetes, smoking, hypertension, dyslipidemia, and family history of heart disease.
That and other findings, Dr. Razavi said, suggest CAC scores in low- to intermediate-risk patients like those studied may sharpen SCD risk-stratification beyond what is possible using traditional risk factors.
Dr. Razavi is lead author on the study’s March 21 publication in JACC Cardiovascular Imaging, and is slated to present the results April 2 during the American College of Cardiology (ACC) 2022 Scientific Session, to be held virtually and in-person in Washington, D.C.
The study’s 66,636 primary-prevention patients, part of the Coronary Artery Calcium Consortium observational cohort, were without known coronary disease at enrollment, from 1991-2010, at four major American centers. They had been referred to CAC imaging because of the presence of at least one ASCVD risk factor, such as dyslipidemia, family history of premature heart disease, hypertension, or diabetes, the researchers note.
They observed 211 SCD events, for a rate of about 0.3%, over a median of 10.6 years. The adjusted stepwise higher risk (SHR) for an SCD event went up continuously with CAC scores (P for trend < .001). The SHR values, compared with a CAC score of 0, were:
- 1.3 (95% CI, 0.7-2.4) for a CAC score score of 1 to 99
- 2.8 (95% CI, 1.6-5.0) for a CAC score of 100 to 399
- 4.0 (95% CI, 2.2-7.3) for a CAC score of 400 to 999
- 4.9 (95% CI, 2.6-9.9) for a CAC score above 1,000
The magnitude of the CAC score’s association with SCD risk in the study was “surprising,” Dr. Razavi said. The CAC score, starting at about 100, seems “more strongly associated with a sudden cardiac arrest” than more familiar SCD risk predictors, such as prolonged heart-rate-corrected QT interval or QRS duration.
Dr. Razavi reported no conflicts. Disclosures for the other authors are in the report.
A version of this article first appeared on Medscape.com.
The risk for sudden cardiac death (SCD) climbs steadily in tandem with coronary artery calcium (CAC) burden, independent of more conventional risk factors, in primary-prevention patients considered low- to intermediate-risk, researchers say.
The findings, based on a large cohort study, strengthen the case for initial CAC imaging as a gatekeeper to further testing in such patients who have mostly subclinical atherosclerotic cardiovascular disease (ASCVD), they conclude.
The CAC scan is “evolving into a primary-prevention screening test, not only for initiating statin therapy, but now as a screening modality for risk stratifying someone for sudden cardiac arrest,” Alexander C. Razavi, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization.
“Our data reinforce this and give some quantitative measures of when we should start to consider that.”
A CAC score of 100 to 399 in this “primarily asymptomatic,” predominantly White and male cohort elevated the risk for SCD over an average of 10.6 years by a factor of 2.8, compared with a score of 0. The risk went up four times with CAC scores of 400-999, and almost five times with scores above 1,000.
The risk association was independent of age and sex but also diabetes, smoking, hypertension, dyslipidemia, and family history of heart disease.
That and other findings, Dr. Razavi said, suggest CAC scores in low- to intermediate-risk patients like those studied may sharpen SCD risk-stratification beyond what is possible using traditional risk factors.
Dr. Razavi is lead author on the study’s March 21 publication in JACC Cardiovascular Imaging, and is slated to present the results April 2 during the American College of Cardiology (ACC) 2022 Scientific Session, to be held virtually and in-person in Washington, D.C.
The study’s 66,636 primary-prevention patients, part of the Coronary Artery Calcium Consortium observational cohort, were without known coronary disease at enrollment, from 1991-2010, at four major American centers. They had been referred to CAC imaging because of the presence of at least one ASCVD risk factor, such as dyslipidemia, family history of premature heart disease, hypertension, or diabetes, the researchers note.
They observed 211 SCD events, for a rate of about 0.3%, over a median of 10.6 years. The adjusted stepwise higher risk (SHR) for an SCD event went up continuously with CAC scores (P for trend < .001). The SHR values, compared with a CAC score of 0, were:
- 1.3 (95% CI, 0.7-2.4) for a CAC score score of 1 to 99
- 2.8 (95% CI, 1.6-5.0) for a CAC score of 100 to 399
- 4.0 (95% CI, 2.2-7.3) for a CAC score of 400 to 999
- 4.9 (95% CI, 2.6-9.9) for a CAC score above 1,000
The magnitude of the CAC score’s association with SCD risk in the study was “surprising,” Dr. Razavi said. The CAC score, starting at about 100, seems “more strongly associated with a sudden cardiac arrest” than more familiar SCD risk predictors, such as prolonged heart-rate-corrected QT interval or QRS duration.
Dr. Razavi reported no conflicts. Disclosures for the other authors are in the report.
A version of this article first appeared on Medscape.com.
The risk for sudden cardiac death (SCD) climbs steadily in tandem with coronary artery calcium (CAC) burden, independent of more conventional risk factors, in primary-prevention patients considered low- to intermediate-risk, researchers say.
The findings, based on a large cohort study, strengthen the case for initial CAC imaging as a gatekeeper to further testing in such patients who have mostly subclinical atherosclerotic cardiovascular disease (ASCVD), they conclude.
The CAC scan is “evolving into a primary-prevention screening test, not only for initiating statin therapy, but now as a screening modality for risk stratifying someone for sudden cardiac arrest,” Alexander C. Razavi, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization.
“Our data reinforce this and give some quantitative measures of when we should start to consider that.”
A CAC score of 100 to 399 in this “primarily asymptomatic,” predominantly White and male cohort elevated the risk for SCD over an average of 10.6 years by a factor of 2.8, compared with a score of 0. The risk went up four times with CAC scores of 400-999, and almost five times with scores above 1,000.
The risk association was independent of age and sex but also diabetes, smoking, hypertension, dyslipidemia, and family history of heart disease.
That and other findings, Dr. Razavi said, suggest CAC scores in low- to intermediate-risk patients like those studied may sharpen SCD risk-stratification beyond what is possible using traditional risk factors.
Dr. Razavi is lead author on the study’s March 21 publication in JACC Cardiovascular Imaging, and is slated to present the results April 2 during the American College of Cardiology (ACC) 2022 Scientific Session, to be held virtually and in-person in Washington, D.C.
The study’s 66,636 primary-prevention patients, part of the Coronary Artery Calcium Consortium observational cohort, were without known coronary disease at enrollment, from 1991-2010, at four major American centers. They had been referred to CAC imaging because of the presence of at least one ASCVD risk factor, such as dyslipidemia, family history of premature heart disease, hypertension, or diabetes, the researchers note.
They observed 211 SCD events, for a rate of about 0.3%, over a median of 10.6 years. The adjusted stepwise higher risk (SHR) for an SCD event went up continuously with CAC scores (P for trend < .001). The SHR values, compared with a CAC score of 0, were:
- 1.3 (95% CI, 0.7-2.4) for a CAC score score of 1 to 99
- 2.8 (95% CI, 1.6-5.0) for a CAC score of 100 to 399
- 4.0 (95% CI, 2.2-7.3) for a CAC score of 400 to 999
- 4.9 (95% CI, 2.6-9.9) for a CAC score above 1,000
The magnitude of the CAC score’s association with SCD risk in the study was “surprising,” Dr. Razavi said. The CAC score, starting at about 100, seems “more strongly associated with a sudden cardiac arrest” than more familiar SCD risk predictors, such as prolonged heart-rate-corrected QT interval or QRS duration.
Dr. Razavi reported no conflicts. Disclosures for the other authors are in the report.
A version of this article first appeared on Medscape.com.
Even light drinking ups CV risk; harm rises along with intake
Even very light alcohol intake is associated with an increased risk for cardiovascular disease, compared with not drinking at all, and the risk increases exponentially as alcohol intake rises, even at moderate levels, a new study shows.
“Our findings suggest that the observed benefit in individuals with light to moderate alcohol intake, which is consistently shown in epidemiological studies, is likely due to other positive lifestyle factors that are common in these individuals who drink lightly,” senior author Krishna Aragam, MD, Massachusetts General Hospital, Boston, told this news organization.
“Our results also showed that while all levels of alcohol were linked to increased risk of cardiovascular disease, the association was not linear. Rather, light alcohol intake was associated with rather modest risk increases, but there were exponential increases in cardiovascular risk with increasing amounts of alcohol consumption,” he said.
As the risk gradient appeared to increase quite sharply even between 1 and 2 drinks per day, Dr. Aragam suggested that what might be regarded as safe levels of drinking may trend downward in the future.
The study was published online March 25 in JAMA Network Open.
The cohort study used data from the UK Biobank, collected between 2006 and 2010 with follow-up until 2016, to assess the relationship between various levels of alcohol consumption and risk for cardiovascular disease.
Data were analyzed from 371,463 participants (mean age, 57 years; 46% men) who consumed an average of 9.2 standard drinks per week. Of these participants, 33% had hypertension and 7.5% had coronary artery disease.
“Use of the UK biobank database gives the advantage of a large, well-phenotyped population with a lot of information on various lifestyle factors that could be potential confounders,” Dr. Aragam noted.
Results showed that well-established J- or U-shaped curves were seen for the association between alcohol consumption and both the prevalence and hazards of hypertension, coronary artery disease, myocardial infarction, stroke, heart failure, and atrial fibrillation.
However, individuals in the light and moderate consumption group had healthier lifestyle behaviors than abstainers, self-reporting better overall health and exhibiting lower rates of smoking, lower body mass index, higher physical activity, and higher vegetable intake.
Adjustment for these lifestyle factors attenuated the cardioprotective associations with modest alcohol intake. For example, in baseline models, moderate intake was associated with significantly lower risk of hypertension and coronary artery disease, but adjustment for just six lifestyle factors rendered these results insignificant.
“Adjustments for yet unmeasured or unknown factors may further attenuate, if not eliminate, the residual, cardioprotective associations observed among light drinkers,” the researchers suggest.
They also conducted genetic analyses to examine the effect of alcohol and cardiovascular disease.
Dr. Aragam explained that previous work has shown good evidence, in individuals who choose to drink, that several relevant genetic variants predict levels of alcohol consumption quite accurately.
“Mendelian randomization using these gene variants allows for stronger inferences about potential causality than do observational studies, as they are less affected by confounding factors,” he noted.
Newer techniques in Mendelian randomization in which data on several gene variants linked to alcohol consumption are combined into a score allow for a greater understanding of the risk linked to different amount of alcohol intake, he added.
In these Mendelian randomization analyses, a 1-standard deviation increase in genetically predicted alcohol consumption was associated with 1.3-fold higher risk of hypertension (P < .001) and 1.4-fold higher risk of coronary artery disease (P = .006).
Further analyses suggested nonlinear associations between alcohol consumption and both hypertension and coronary artery disease; light alcohol intake was associated with minimal increases in cardiovascular risk, whereas heavier consumption was associated with exponential increases in risk of both clinical and subclinical cardiovascular disease.
These results were replicated in a second database of 30,716 individuals from the Mass General Brigham Biobank.
“The findings of this study suggest that the observed cardioprotective effects of light to moderate alcohol intake may be largely mediated by confounding lifestyle factors,” the researchers conclude. “Genetic analyses suggest causal associations between alcohol intake and cardiovascular disease but with unequal and exponential increases in risk at greater levels of intake, which should be accounted for in health recommendations around the habitual consumption of alcohol.”
What is an acceptable level?
“Specifically, our results suggest that consuming as many as 7 drinks per week is associated with relatively modest increases in cardiovascular risk,” they write.
But they point out that there are unequal increases in cardiovascular risk when progressing from 0 to 7 versus 7 to 14 drinks per week in both men and women.
“Although risk thresholds are inherently somewhat subjective, these findings again bring into question whether an average consumption of 2 drinks per day (14 drinks per week) should be designated a low-risk behavior,” they say.
“Furthermore, as several-fold increases in risk were observed for those consuming 21 or more drinks per week, our results emphasize the importance of aggressive efforts to reduce alcohol intake among heavy drinkers,” they add.
Dr. Aragam elaborated: “Our data suggest that reducing alcohol intake will reduce cardiovascular risk in all individuals, but the extent of the relative risk reduction is quite different depending on the current levels of consumption. For the same absolute reduction in alcohol intake, the gains in terms of reduction in cardiovascular risk will be more pronounced in those who drink heavily and will be more modest in those who drink at a light level.”
The results also suggest that while all levels of alcohol intake increase cardiovascular risk, there are low levels of alcohol consumption that do not carry major elevations in risk, but these are probably lower than those currently recommended, Dr. Aragam pointed out.
“This doesn’t mean that everyone has to give up drinking alcohol completely, just that you shouldn’t consume with the goal of improving cardiovascular health. In fact, our analyses suggest that in an otherwise healthy person, up to 1 drink per day may not pose outsized risks,” he said. “And, even in a less healthy person who might be smoking, eating poorly, and drinking up to 1 drink per day, it may be a higher priority to focus on smoking cessation and diet than cutting back further on alcohol.”
“Beyond that amount, though, the jury is still out. Our models suggested marked increases in risk even between 1 and 2 drinks per day, and of course even greater risk increases beyond that. So, it’s probably worth revisiting what one might consider a ‘safe’ amount within the moderate drinking categories. The conservative move for now might be to advise a limit of 1 drink per day,” he said.
Dr. Aragam is supported by grants from the National Institutes of Health and the American Heart Association. He reports receiving speaking fees from the Novartis Institute for Biomedical Research.
A version of this article first appeared on Medscape.com.
Even very light alcohol intake is associated with an increased risk for cardiovascular disease, compared with not drinking at all, and the risk increases exponentially as alcohol intake rises, even at moderate levels, a new study shows.
“Our findings suggest that the observed benefit in individuals with light to moderate alcohol intake, which is consistently shown in epidemiological studies, is likely due to other positive lifestyle factors that are common in these individuals who drink lightly,” senior author Krishna Aragam, MD, Massachusetts General Hospital, Boston, told this news organization.
“Our results also showed that while all levels of alcohol were linked to increased risk of cardiovascular disease, the association was not linear. Rather, light alcohol intake was associated with rather modest risk increases, but there were exponential increases in cardiovascular risk with increasing amounts of alcohol consumption,” he said.
As the risk gradient appeared to increase quite sharply even between 1 and 2 drinks per day, Dr. Aragam suggested that what might be regarded as safe levels of drinking may trend downward in the future.
The study was published online March 25 in JAMA Network Open.
The cohort study used data from the UK Biobank, collected between 2006 and 2010 with follow-up until 2016, to assess the relationship between various levels of alcohol consumption and risk for cardiovascular disease.
Data were analyzed from 371,463 participants (mean age, 57 years; 46% men) who consumed an average of 9.2 standard drinks per week. Of these participants, 33% had hypertension and 7.5% had coronary artery disease.
“Use of the UK biobank database gives the advantage of a large, well-phenotyped population with a lot of information on various lifestyle factors that could be potential confounders,” Dr. Aragam noted.
Results showed that well-established J- or U-shaped curves were seen for the association between alcohol consumption and both the prevalence and hazards of hypertension, coronary artery disease, myocardial infarction, stroke, heart failure, and atrial fibrillation.
However, individuals in the light and moderate consumption group had healthier lifestyle behaviors than abstainers, self-reporting better overall health and exhibiting lower rates of smoking, lower body mass index, higher physical activity, and higher vegetable intake.
Adjustment for these lifestyle factors attenuated the cardioprotective associations with modest alcohol intake. For example, in baseline models, moderate intake was associated with significantly lower risk of hypertension and coronary artery disease, but adjustment for just six lifestyle factors rendered these results insignificant.
“Adjustments for yet unmeasured or unknown factors may further attenuate, if not eliminate, the residual, cardioprotective associations observed among light drinkers,” the researchers suggest.
They also conducted genetic analyses to examine the effect of alcohol and cardiovascular disease.
Dr. Aragam explained that previous work has shown good evidence, in individuals who choose to drink, that several relevant genetic variants predict levels of alcohol consumption quite accurately.
“Mendelian randomization using these gene variants allows for stronger inferences about potential causality than do observational studies, as they are less affected by confounding factors,” he noted.
Newer techniques in Mendelian randomization in which data on several gene variants linked to alcohol consumption are combined into a score allow for a greater understanding of the risk linked to different amount of alcohol intake, he added.
In these Mendelian randomization analyses, a 1-standard deviation increase in genetically predicted alcohol consumption was associated with 1.3-fold higher risk of hypertension (P < .001) and 1.4-fold higher risk of coronary artery disease (P = .006).
Further analyses suggested nonlinear associations between alcohol consumption and both hypertension and coronary artery disease; light alcohol intake was associated with minimal increases in cardiovascular risk, whereas heavier consumption was associated with exponential increases in risk of both clinical and subclinical cardiovascular disease.
These results were replicated in a second database of 30,716 individuals from the Mass General Brigham Biobank.
“The findings of this study suggest that the observed cardioprotective effects of light to moderate alcohol intake may be largely mediated by confounding lifestyle factors,” the researchers conclude. “Genetic analyses suggest causal associations between alcohol intake and cardiovascular disease but with unequal and exponential increases in risk at greater levels of intake, which should be accounted for in health recommendations around the habitual consumption of alcohol.”
What is an acceptable level?
“Specifically, our results suggest that consuming as many as 7 drinks per week is associated with relatively modest increases in cardiovascular risk,” they write.
But they point out that there are unequal increases in cardiovascular risk when progressing from 0 to 7 versus 7 to 14 drinks per week in both men and women.
“Although risk thresholds are inherently somewhat subjective, these findings again bring into question whether an average consumption of 2 drinks per day (14 drinks per week) should be designated a low-risk behavior,” they say.
“Furthermore, as several-fold increases in risk were observed for those consuming 21 or more drinks per week, our results emphasize the importance of aggressive efforts to reduce alcohol intake among heavy drinkers,” they add.
Dr. Aragam elaborated: “Our data suggest that reducing alcohol intake will reduce cardiovascular risk in all individuals, but the extent of the relative risk reduction is quite different depending on the current levels of consumption. For the same absolute reduction in alcohol intake, the gains in terms of reduction in cardiovascular risk will be more pronounced in those who drink heavily and will be more modest in those who drink at a light level.”
The results also suggest that while all levels of alcohol intake increase cardiovascular risk, there are low levels of alcohol consumption that do not carry major elevations in risk, but these are probably lower than those currently recommended, Dr. Aragam pointed out.
“This doesn’t mean that everyone has to give up drinking alcohol completely, just that you shouldn’t consume with the goal of improving cardiovascular health. In fact, our analyses suggest that in an otherwise healthy person, up to 1 drink per day may not pose outsized risks,” he said. “And, even in a less healthy person who might be smoking, eating poorly, and drinking up to 1 drink per day, it may be a higher priority to focus on smoking cessation and diet than cutting back further on alcohol.”
“Beyond that amount, though, the jury is still out. Our models suggested marked increases in risk even between 1 and 2 drinks per day, and of course even greater risk increases beyond that. So, it’s probably worth revisiting what one might consider a ‘safe’ amount within the moderate drinking categories. The conservative move for now might be to advise a limit of 1 drink per day,” he said.
Dr. Aragam is supported by grants from the National Institutes of Health and the American Heart Association. He reports receiving speaking fees from the Novartis Institute for Biomedical Research.
A version of this article first appeared on Medscape.com.
Even very light alcohol intake is associated with an increased risk for cardiovascular disease, compared with not drinking at all, and the risk increases exponentially as alcohol intake rises, even at moderate levels, a new study shows.
“Our findings suggest that the observed benefit in individuals with light to moderate alcohol intake, which is consistently shown in epidemiological studies, is likely due to other positive lifestyle factors that are common in these individuals who drink lightly,” senior author Krishna Aragam, MD, Massachusetts General Hospital, Boston, told this news organization.
“Our results also showed that while all levels of alcohol were linked to increased risk of cardiovascular disease, the association was not linear. Rather, light alcohol intake was associated with rather modest risk increases, but there were exponential increases in cardiovascular risk with increasing amounts of alcohol consumption,” he said.
As the risk gradient appeared to increase quite sharply even between 1 and 2 drinks per day, Dr. Aragam suggested that what might be regarded as safe levels of drinking may trend downward in the future.
The study was published online March 25 in JAMA Network Open.
The cohort study used data from the UK Biobank, collected between 2006 and 2010 with follow-up until 2016, to assess the relationship between various levels of alcohol consumption and risk for cardiovascular disease.
Data were analyzed from 371,463 participants (mean age, 57 years; 46% men) who consumed an average of 9.2 standard drinks per week. Of these participants, 33% had hypertension and 7.5% had coronary artery disease.
“Use of the UK biobank database gives the advantage of a large, well-phenotyped population with a lot of information on various lifestyle factors that could be potential confounders,” Dr. Aragam noted.
Results showed that well-established J- or U-shaped curves were seen for the association between alcohol consumption and both the prevalence and hazards of hypertension, coronary artery disease, myocardial infarction, stroke, heart failure, and atrial fibrillation.
However, individuals in the light and moderate consumption group had healthier lifestyle behaviors than abstainers, self-reporting better overall health and exhibiting lower rates of smoking, lower body mass index, higher physical activity, and higher vegetable intake.
Adjustment for these lifestyle factors attenuated the cardioprotective associations with modest alcohol intake. For example, in baseline models, moderate intake was associated with significantly lower risk of hypertension and coronary artery disease, but adjustment for just six lifestyle factors rendered these results insignificant.
“Adjustments for yet unmeasured or unknown factors may further attenuate, if not eliminate, the residual, cardioprotective associations observed among light drinkers,” the researchers suggest.
They also conducted genetic analyses to examine the effect of alcohol and cardiovascular disease.
Dr. Aragam explained that previous work has shown good evidence, in individuals who choose to drink, that several relevant genetic variants predict levels of alcohol consumption quite accurately.
“Mendelian randomization using these gene variants allows for stronger inferences about potential causality than do observational studies, as they are less affected by confounding factors,” he noted.
Newer techniques in Mendelian randomization in which data on several gene variants linked to alcohol consumption are combined into a score allow for a greater understanding of the risk linked to different amount of alcohol intake, he added.
In these Mendelian randomization analyses, a 1-standard deviation increase in genetically predicted alcohol consumption was associated with 1.3-fold higher risk of hypertension (P < .001) and 1.4-fold higher risk of coronary artery disease (P = .006).
Further analyses suggested nonlinear associations between alcohol consumption and both hypertension and coronary artery disease; light alcohol intake was associated with minimal increases in cardiovascular risk, whereas heavier consumption was associated with exponential increases in risk of both clinical and subclinical cardiovascular disease.
These results were replicated in a second database of 30,716 individuals from the Mass General Brigham Biobank.
“The findings of this study suggest that the observed cardioprotective effects of light to moderate alcohol intake may be largely mediated by confounding lifestyle factors,” the researchers conclude. “Genetic analyses suggest causal associations between alcohol intake and cardiovascular disease but with unequal and exponential increases in risk at greater levels of intake, which should be accounted for in health recommendations around the habitual consumption of alcohol.”
What is an acceptable level?
“Specifically, our results suggest that consuming as many as 7 drinks per week is associated with relatively modest increases in cardiovascular risk,” they write.
But they point out that there are unequal increases in cardiovascular risk when progressing from 0 to 7 versus 7 to 14 drinks per week in both men and women.
“Although risk thresholds are inherently somewhat subjective, these findings again bring into question whether an average consumption of 2 drinks per day (14 drinks per week) should be designated a low-risk behavior,” they say.
“Furthermore, as several-fold increases in risk were observed for those consuming 21 or more drinks per week, our results emphasize the importance of aggressive efforts to reduce alcohol intake among heavy drinkers,” they add.
Dr. Aragam elaborated: “Our data suggest that reducing alcohol intake will reduce cardiovascular risk in all individuals, but the extent of the relative risk reduction is quite different depending on the current levels of consumption. For the same absolute reduction in alcohol intake, the gains in terms of reduction in cardiovascular risk will be more pronounced in those who drink heavily and will be more modest in those who drink at a light level.”
The results also suggest that while all levels of alcohol intake increase cardiovascular risk, there are low levels of alcohol consumption that do not carry major elevations in risk, but these are probably lower than those currently recommended, Dr. Aragam pointed out.
“This doesn’t mean that everyone has to give up drinking alcohol completely, just that you shouldn’t consume with the goal of improving cardiovascular health. In fact, our analyses suggest that in an otherwise healthy person, up to 1 drink per day may not pose outsized risks,” he said. “And, even in a less healthy person who might be smoking, eating poorly, and drinking up to 1 drink per day, it may be a higher priority to focus on smoking cessation and diet than cutting back further on alcohol.”
“Beyond that amount, though, the jury is still out. Our models suggested marked increases in risk even between 1 and 2 drinks per day, and of course even greater risk increases beyond that. So, it’s probably worth revisiting what one might consider a ‘safe’ amount within the moderate drinking categories. The conservative move for now might be to advise a limit of 1 drink per day,” he said.
Dr. Aragam is supported by grants from the National Institutes of Health and the American Heart Association. He reports receiving speaking fees from the Novartis Institute for Biomedical Research.
A version of this article first appeared on Medscape.com.
Be aware of gallbladder, biliary disease with newer obesity drugs
Treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with a 37% increase in the relative risk of gallbladder or biliary disease, compared with controls – especially when used at high doses, for a longer time, and for weight loss rather than type 2 diabetes – a new meta-analysis has found.
The results “indicate that physicians and patients should be concerned about the risks of gallbladder or biliary diseases with using GLP-1 agonists,” study authors Liyun He and colleagues from Peking Union Medical College, Beijing, summarize.
However, “the overall absolute risk increase for gallbladder and biliary disease with use of GLP-1 receptor agonists was small (an additional 27 cases per 10,000 persons treated per year),” they note.
“This absolute risk increase should be weighed against the benefits of treatment with GLP-1 agonists,” which include glucose control, decreased cardiovascular risk, and weight loss, they add.
The findings are from a meta-analysis of 76 randomized controlled trials of GLP-1 agonists published online March 28 in JAMA Internal Medicine.
In an accompanying editorial, Shanzay Haider, MD, and Kasia J. Lipska, MD, also characterize the absolute risk of these complications as “modest.”
“The highest risk for these complications,” they add, “occurred among individuals in the weight loss, compared with the type 2 diabetes studies (119 vs. 13 more events per 10,000 persons per year).”
“Ultimately, the decision to start, continue, or change the dose of a GLP-1 agonist should be reached through a collaborative and individualized discussion between a clinician and a patient,” Dr. Haider and Dr. Lipska, from Yale School of Medicine, New Haven, Conn., summarize.
The study authors also note that few of the trials reported biliary-related events.
“Future trials [of drugs in this class] should prespecify gallbladder and biliary diseases as potential adverse events, and fully test for and report on these outcomes,” they urge.
Certain drugs in this class are now approved by the U.S. Food and Drug Administration for weight loss at higher doses than for type 2 diabetes – subcutaneous liraglutide (3.0 mg) and subcutaneous semaglutide (2.4 mg) – “suggesting that GLP-1 agonist drugs will increasingly be used at high doses for weight control,” the authors note.
Controversial link
The association between GLP-1 agonists and gallbladder or biliary disease is controversial, the authors write.
Several randomized controlled trials reported higher rates of gallbladder disorders in patients who received a GLP-1 agonist versus placebo, but it is not clear if this is a class effect.
Liraglutide “has drawn the most attention” about this risk, and a post-hoc analysis of the LEADER trial found a significantly increased risk of acute biliary obstruction with liraglutide versus placebo.
To investigate this, the researchers identified 76 randomized controlled trials of GLP-1 agonists in 103,371 patients that had data for the following safety outcomes: cholelithiasis (gallstones, 61 trials), cholecystitis (inflamed gallbladder, 53 trials), biliary disease (21 trials), cholecystectomy (surgical removal of the gallbladder, seven trials), and biliary cancer (12 trials).
Sixty trials were for type 2 diabetes, 13 were for weight loss, and three were for nonalcoholic steatohepatitis, polycystic ovary syndrome, and schizophrenia. They were classed as short or long (≤ 26 weeks or > 26 weeks).
The GLP-1 agonists were liraglutide (21 trials), subcutaneous semaglutide (14), dulaglutide (11), exenatide (9), albiglutide (8), oral semaglutide (8), and lixisenatide (6).
Participants were a mean age of 58 years and 41% were women. They had a mean BMI of 31.6 kg/m2 and 36.9 kg/m2 in trials of GLP-1 agonists for type 2 diabetes and weight loss, respectively.
Patients who received a GLP-1 agonist versus controls had significantly increased rates of cholelithiasis (RR, 1.27; P = .001), cholecystitis (RR, 1.36; P < .001), biliary disease (RR, 1.55; P = .02), and cholecystectomy (RR, 1.70; P < .001) but a nonsignificant increased rate of biliary cancer (RR, 1.43; P = .22).
Use of GLP-1 agonists was associated with a greater increased risk of gallbladder or biliary diseases in trials for weight loss (RR, 2.29) than in trials for type 2 diabetes or other diseases (RR, 1.27; P < .001 for interaction).
Use of these drugs was also associated with higher risks of these complications at higher doses and when given for a longer duration.
Limitations of the meta-analysis include that the individual studies were not designed to evaluate the risk of gallbladder or biliary diseases associated with GLP-1 agonists.
Also, biliary-related events may have been under-reported, because this was not a predefined safety outcome in most of the trials. The meta-analysis lacked patient-level data, and it may have been underpowered for subgroup analyses.
The work was supported by grants from the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences, the CAMS Innovation Fund for Medical Sciences, and the Training Program for Excellent Talents in Dongcheng District. The researchers have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with a 37% increase in the relative risk of gallbladder or biliary disease, compared with controls – especially when used at high doses, for a longer time, and for weight loss rather than type 2 diabetes – a new meta-analysis has found.
The results “indicate that physicians and patients should be concerned about the risks of gallbladder or biliary diseases with using GLP-1 agonists,” study authors Liyun He and colleagues from Peking Union Medical College, Beijing, summarize.
However, “the overall absolute risk increase for gallbladder and biliary disease with use of GLP-1 receptor agonists was small (an additional 27 cases per 10,000 persons treated per year),” they note.
“This absolute risk increase should be weighed against the benefits of treatment with GLP-1 agonists,” which include glucose control, decreased cardiovascular risk, and weight loss, they add.
The findings are from a meta-analysis of 76 randomized controlled trials of GLP-1 agonists published online March 28 in JAMA Internal Medicine.
In an accompanying editorial, Shanzay Haider, MD, and Kasia J. Lipska, MD, also characterize the absolute risk of these complications as “modest.”
“The highest risk for these complications,” they add, “occurred among individuals in the weight loss, compared with the type 2 diabetes studies (119 vs. 13 more events per 10,000 persons per year).”
“Ultimately, the decision to start, continue, or change the dose of a GLP-1 agonist should be reached through a collaborative and individualized discussion between a clinician and a patient,” Dr. Haider and Dr. Lipska, from Yale School of Medicine, New Haven, Conn., summarize.
The study authors also note that few of the trials reported biliary-related events.
“Future trials [of drugs in this class] should prespecify gallbladder and biliary diseases as potential adverse events, and fully test for and report on these outcomes,” they urge.
Certain drugs in this class are now approved by the U.S. Food and Drug Administration for weight loss at higher doses than for type 2 diabetes – subcutaneous liraglutide (3.0 mg) and subcutaneous semaglutide (2.4 mg) – “suggesting that GLP-1 agonist drugs will increasingly be used at high doses for weight control,” the authors note.
Controversial link
The association between GLP-1 agonists and gallbladder or biliary disease is controversial, the authors write.
Several randomized controlled trials reported higher rates of gallbladder disorders in patients who received a GLP-1 agonist versus placebo, but it is not clear if this is a class effect.
Liraglutide “has drawn the most attention” about this risk, and a post-hoc analysis of the LEADER trial found a significantly increased risk of acute biliary obstruction with liraglutide versus placebo.
To investigate this, the researchers identified 76 randomized controlled trials of GLP-1 agonists in 103,371 patients that had data for the following safety outcomes: cholelithiasis (gallstones, 61 trials), cholecystitis (inflamed gallbladder, 53 trials), biliary disease (21 trials), cholecystectomy (surgical removal of the gallbladder, seven trials), and biliary cancer (12 trials).
Sixty trials were for type 2 diabetes, 13 were for weight loss, and three were for nonalcoholic steatohepatitis, polycystic ovary syndrome, and schizophrenia. They were classed as short or long (≤ 26 weeks or > 26 weeks).
The GLP-1 agonists were liraglutide (21 trials), subcutaneous semaglutide (14), dulaglutide (11), exenatide (9), albiglutide (8), oral semaglutide (8), and lixisenatide (6).
Participants were a mean age of 58 years and 41% were women. They had a mean BMI of 31.6 kg/m2 and 36.9 kg/m2 in trials of GLP-1 agonists for type 2 diabetes and weight loss, respectively.
Patients who received a GLP-1 agonist versus controls had significantly increased rates of cholelithiasis (RR, 1.27; P = .001), cholecystitis (RR, 1.36; P < .001), biliary disease (RR, 1.55; P = .02), and cholecystectomy (RR, 1.70; P < .001) but a nonsignificant increased rate of biliary cancer (RR, 1.43; P = .22).
Use of GLP-1 agonists was associated with a greater increased risk of gallbladder or biliary diseases in trials for weight loss (RR, 2.29) than in trials for type 2 diabetes or other diseases (RR, 1.27; P < .001 for interaction).
Use of these drugs was also associated with higher risks of these complications at higher doses and when given for a longer duration.
Limitations of the meta-analysis include that the individual studies were not designed to evaluate the risk of gallbladder or biliary diseases associated with GLP-1 agonists.
Also, biliary-related events may have been under-reported, because this was not a predefined safety outcome in most of the trials. The meta-analysis lacked patient-level data, and it may have been underpowered for subgroup analyses.
The work was supported by grants from the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences, the CAMS Innovation Fund for Medical Sciences, and the Training Program for Excellent Talents in Dongcheng District. The researchers have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with a 37% increase in the relative risk of gallbladder or biliary disease, compared with controls – especially when used at high doses, for a longer time, and for weight loss rather than type 2 diabetes – a new meta-analysis has found.
The results “indicate that physicians and patients should be concerned about the risks of gallbladder or biliary diseases with using GLP-1 agonists,” study authors Liyun He and colleagues from Peking Union Medical College, Beijing, summarize.
However, “the overall absolute risk increase for gallbladder and biliary disease with use of GLP-1 receptor agonists was small (an additional 27 cases per 10,000 persons treated per year),” they note.
“This absolute risk increase should be weighed against the benefits of treatment with GLP-1 agonists,” which include glucose control, decreased cardiovascular risk, and weight loss, they add.
The findings are from a meta-analysis of 76 randomized controlled trials of GLP-1 agonists published online March 28 in JAMA Internal Medicine.
In an accompanying editorial, Shanzay Haider, MD, and Kasia J. Lipska, MD, also characterize the absolute risk of these complications as “modest.”
“The highest risk for these complications,” they add, “occurred among individuals in the weight loss, compared with the type 2 diabetes studies (119 vs. 13 more events per 10,000 persons per year).”
“Ultimately, the decision to start, continue, or change the dose of a GLP-1 agonist should be reached through a collaborative and individualized discussion between a clinician and a patient,” Dr. Haider and Dr. Lipska, from Yale School of Medicine, New Haven, Conn., summarize.
The study authors also note that few of the trials reported biliary-related events.
“Future trials [of drugs in this class] should prespecify gallbladder and biliary diseases as potential adverse events, and fully test for and report on these outcomes,” they urge.
Certain drugs in this class are now approved by the U.S. Food and Drug Administration for weight loss at higher doses than for type 2 diabetes – subcutaneous liraglutide (3.0 mg) and subcutaneous semaglutide (2.4 mg) – “suggesting that GLP-1 agonist drugs will increasingly be used at high doses for weight control,” the authors note.
Controversial link
The association between GLP-1 agonists and gallbladder or biliary disease is controversial, the authors write.
Several randomized controlled trials reported higher rates of gallbladder disorders in patients who received a GLP-1 agonist versus placebo, but it is not clear if this is a class effect.
Liraglutide “has drawn the most attention” about this risk, and a post-hoc analysis of the LEADER trial found a significantly increased risk of acute biliary obstruction with liraglutide versus placebo.
To investigate this, the researchers identified 76 randomized controlled trials of GLP-1 agonists in 103,371 patients that had data for the following safety outcomes: cholelithiasis (gallstones, 61 trials), cholecystitis (inflamed gallbladder, 53 trials), biliary disease (21 trials), cholecystectomy (surgical removal of the gallbladder, seven trials), and biliary cancer (12 trials).
Sixty trials were for type 2 diabetes, 13 were for weight loss, and three were for nonalcoholic steatohepatitis, polycystic ovary syndrome, and schizophrenia. They were classed as short or long (≤ 26 weeks or > 26 weeks).
The GLP-1 agonists were liraglutide (21 trials), subcutaneous semaglutide (14), dulaglutide (11), exenatide (9), albiglutide (8), oral semaglutide (8), and lixisenatide (6).
Participants were a mean age of 58 years and 41% were women. They had a mean BMI of 31.6 kg/m2 and 36.9 kg/m2 in trials of GLP-1 agonists for type 2 diabetes and weight loss, respectively.
Patients who received a GLP-1 agonist versus controls had significantly increased rates of cholelithiasis (RR, 1.27; P = .001), cholecystitis (RR, 1.36; P < .001), biliary disease (RR, 1.55; P = .02), and cholecystectomy (RR, 1.70; P < .001) but a nonsignificant increased rate of biliary cancer (RR, 1.43; P = .22).
Use of GLP-1 agonists was associated with a greater increased risk of gallbladder or biliary diseases in trials for weight loss (RR, 2.29) than in trials for type 2 diabetes or other diseases (RR, 1.27; P < .001 for interaction).
Use of these drugs was also associated with higher risks of these complications at higher doses and when given for a longer duration.
Limitations of the meta-analysis include that the individual studies were not designed to evaluate the risk of gallbladder or biliary diseases associated with GLP-1 agonists.
Also, biliary-related events may have been under-reported, because this was not a predefined safety outcome in most of the trials. The meta-analysis lacked patient-level data, and it may have been underpowered for subgroup analyses.
The work was supported by grants from the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences, the CAMS Innovation Fund for Medical Sciences, and the Training Program for Excellent Talents in Dongcheng District. The researchers have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Hybrid ACC 2022 resurrects the live scientific session
Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.
They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.
That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.
Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.
They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.
Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.
On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)
Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.
The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.
Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.
The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.
SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.
In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.
CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.
The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A
This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.
REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.
They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.
The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)
The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.
“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”
SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.
In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.
Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70; the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).
The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)
The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO2.
The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.
This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.
Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.
Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D
The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.
Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.
Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV
This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).
Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”
Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
Monday, April 4, 11:00–12:15 p.m. LBCT V
This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.
Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,
Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.
The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A
The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.
There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.
A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”
The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.
A version of this article first appeared on Medscape.com.
Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.
They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.
That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.
Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.
They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.
Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.
On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)
Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.
The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.
Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.
The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.
SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.
In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.
CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.
The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A
This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.
REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.
They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.
The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)
The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.
“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”
SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.
In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.
Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70; the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).
The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)
The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO2.
The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.
This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.
Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.
Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D
The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.
Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.
Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV
This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).
Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”
Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
Monday, April 4, 11:00–12:15 p.m. LBCT V
This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.
Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,
Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.
The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A
The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.
There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.
A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”
The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.
A version of this article first appeared on Medscape.com.
Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.
They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.
That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.
Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.
They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.
Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.
On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)
Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.
The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.
Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.
The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.
SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.
In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.
CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.
The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A
This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.
REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.
They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.
The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)
The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.
“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”
SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.
In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.
Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70; the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).
The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)
The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO2.
The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.
This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.
Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.
Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D
The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.
Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.
Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV
This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).
Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”
Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
Monday, April 4, 11:00–12:15 p.m. LBCT V
This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.
Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,
Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.
The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A
The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.
There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.
A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”
The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.
A version of this article first appeared on Medscape.com.
Sleep deprivation sends fat to the belly
A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.
Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.
“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.
“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”
The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm2 increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm2; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.
VAT findings post recovery
After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm2 by day 21.
The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”
The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.
Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.
“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”
In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.
“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.
“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.
The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.
A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.
Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.
“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.
“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”
The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm2 increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm2; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.
VAT findings post recovery
After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm2 by day 21.
The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”
The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.
Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.
“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”
In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.
“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.
“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.
The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.
A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.
Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.
“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.
“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”
The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm2 increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm2; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.
VAT findings post recovery
After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm2 by day 21.
The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”
The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.
Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.
“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”
In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.
“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.
“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.
The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Coffee drinking may cut heart disease risk, prolong survival
A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.
People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.
In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.
In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.
Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”
Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.
UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.
“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.
The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.
The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.
“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”
But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”
Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”
Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
Benefits with or without known heart disease
The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.
Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).
The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).
A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).
Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).
In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.
The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).
Potential mechanisms, study limitations
“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”
Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.
However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.
They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.
A version of this article first appeared on Medscape.com.
A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.
People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.
In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.
In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.
Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”
Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.
UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.
“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.
The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.
The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.
“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”
But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”
Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”
Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
Benefits with or without known heart disease
The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.
Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).
The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).
A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).
Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).
In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.
The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).
Potential mechanisms, study limitations
“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”
Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.
However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.
They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.
A version of this article first appeared on Medscape.com.
A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.
People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.
In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.
In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.
Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”
Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.
UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.
“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.
The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.
The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.
“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”
But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”
Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”
Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
Benefits with or without known heart disease
The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.
Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).
The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).
A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).
Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).
In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.
The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).
Potential mechanisms, study limitations
“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”
Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.
However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.
They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.
A version of this article first appeared on Medscape.com.
FROM ACC 2022
Pfizer recalls BP drugs because of potential carcinogen
Pfizer is voluntarily recalling some antihypertensive medications because of unacceptable levels of a potential carcinogen, the company announced.
The affected products are quinapril HCI/hydrochlorothiazide (Accuretic) tablets that Pfizer distributes, and two authorized generics, quinapril plus hydrochlorothiazide and quinapril HCI/hydrochlorothiazide, distributed by Greenstone. The drugs have been withdrawn because of the presence of nitrosamine, N-nitroso-quinapril.
“Although long-term ingestion of N-nitroso-quinapril may be associated with a potential increased cancer risk in humans, there is no immediate risk to patients taking this medication,” Pfizer said in a news release.
The tablets are indicated for the treatment of hypertension. Patients currently taking the products are asked to consult with their doctor about alternative treatment options.
To date, there have been no reports of adverse events related to the recall, the company said.
In all, Pfizer is recalling six lots of Accuretic tablets (two at 10 mg/12.5 mg, three at 20 mg/12.5 mg, and one at 20 mg/25 mg), one lot of quinapril plus hydrochlorothiazide 20-mg/25-mg tablets, and four lots of quinapril HCl/ hydrochlorothiazide tablets (three at 20 mg/12.5 mg and one at 20 mg/25 mg)
The recalled tablets were sold in 90-count bottles distributed in the United States and Puerto Rico between November 2019 and March 2022. Product codes and lot numbers of the recalled medications are listed on the Pfizer website.
Patients who are taking this product should consult with their health care provider or pharmacy to determine if they have the affected product. Those with the affected tablets should contact claims management firm Sedgwick by phone at 888-843-0247 Monday through Friday from 8 a.m. to 5 p.m. ET for instructions on how to return their product and obtain reimbursement.
Health care providers with medical questions regarding the recall can contact Pfizer by telephone at 800-438-1985, option 3, Monday through Friday 8 a.m. to 9 p.m. ET.
Providers should report adverse reactions or quality problems they experience using these tablets to Pfizer either by telephone at 800-438-1985, option 1, by regular mail or by fax, or to the Food and Drug Administration’s MedWatch program.
A version of this article first appeared on Medscape.com.
Pfizer is voluntarily recalling some antihypertensive medications because of unacceptable levels of a potential carcinogen, the company announced.
The affected products are quinapril HCI/hydrochlorothiazide (Accuretic) tablets that Pfizer distributes, and two authorized generics, quinapril plus hydrochlorothiazide and quinapril HCI/hydrochlorothiazide, distributed by Greenstone. The drugs have been withdrawn because of the presence of nitrosamine, N-nitroso-quinapril.
“Although long-term ingestion of N-nitroso-quinapril may be associated with a potential increased cancer risk in humans, there is no immediate risk to patients taking this medication,” Pfizer said in a news release.
The tablets are indicated for the treatment of hypertension. Patients currently taking the products are asked to consult with their doctor about alternative treatment options.
To date, there have been no reports of adverse events related to the recall, the company said.
In all, Pfizer is recalling six lots of Accuretic tablets (two at 10 mg/12.5 mg, three at 20 mg/12.5 mg, and one at 20 mg/25 mg), one lot of quinapril plus hydrochlorothiazide 20-mg/25-mg tablets, and four lots of quinapril HCl/ hydrochlorothiazide tablets (three at 20 mg/12.5 mg and one at 20 mg/25 mg)
The recalled tablets were sold in 90-count bottles distributed in the United States and Puerto Rico between November 2019 and March 2022. Product codes and lot numbers of the recalled medications are listed on the Pfizer website.
Patients who are taking this product should consult with their health care provider or pharmacy to determine if they have the affected product. Those with the affected tablets should contact claims management firm Sedgwick by phone at 888-843-0247 Monday through Friday from 8 a.m. to 5 p.m. ET for instructions on how to return their product and obtain reimbursement.
Health care providers with medical questions regarding the recall can contact Pfizer by telephone at 800-438-1985, option 3, Monday through Friday 8 a.m. to 9 p.m. ET.
Providers should report adverse reactions or quality problems they experience using these tablets to Pfizer either by telephone at 800-438-1985, option 1, by regular mail or by fax, or to the Food and Drug Administration’s MedWatch program.
A version of this article first appeared on Medscape.com.
Pfizer is voluntarily recalling some antihypertensive medications because of unacceptable levels of a potential carcinogen, the company announced.
The affected products are quinapril HCI/hydrochlorothiazide (Accuretic) tablets that Pfizer distributes, and two authorized generics, quinapril plus hydrochlorothiazide and quinapril HCI/hydrochlorothiazide, distributed by Greenstone. The drugs have been withdrawn because of the presence of nitrosamine, N-nitroso-quinapril.
“Although long-term ingestion of N-nitroso-quinapril may be associated with a potential increased cancer risk in humans, there is no immediate risk to patients taking this medication,” Pfizer said in a news release.
The tablets are indicated for the treatment of hypertension. Patients currently taking the products are asked to consult with their doctor about alternative treatment options.
To date, there have been no reports of adverse events related to the recall, the company said.
In all, Pfizer is recalling six lots of Accuretic tablets (two at 10 mg/12.5 mg, three at 20 mg/12.5 mg, and one at 20 mg/25 mg), one lot of quinapril plus hydrochlorothiazide 20-mg/25-mg tablets, and four lots of quinapril HCl/ hydrochlorothiazide tablets (three at 20 mg/12.5 mg and one at 20 mg/25 mg)
The recalled tablets were sold in 90-count bottles distributed in the United States and Puerto Rico between November 2019 and March 2022. Product codes and lot numbers of the recalled medications are listed on the Pfizer website.
Patients who are taking this product should consult with their health care provider or pharmacy to determine if they have the affected product. Those with the affected tablets should contact claims management firm Sedgwick by phone at 888-843-0247 Monday through Friday from 8 a.m. to 5 p.m. ET for instructions on how to return their product and obtain reimbursement.
Health care providers with medical questions regarding the recall can contact Pfizer by telephone at 800-438-1985, option 3, Monday through Friday 8 a.m. to 9 p.m. ET.
Providers should report adverse reactions or quality problems they experience using these tablets to Pfizer either by telephone at 800-438-1985, option 1, by regular mail or by fax, or to the Food and Drug Administration’s MedWatch program.
A version of this article first appeared on Medscape.com.