CAD & Atherosclerosis

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.

Kirby Hamilton/iStockphoto

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.

Kirby Hamilton/iStockphoto

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.

Kirby Hamilton/iStockphoto

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.

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.

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.

S_Bachstroem/Getty Images

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.

S_Bachstroem/Getty Images

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.

S_Bachstroem/Getty Images

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 sudden drop in blood pressure when standing is a common and concerning problem in elderly hypertensive people. Now, research suggests a large BP swing in the opposite direction on standing may be equally concerning in younger hypertensive people.

Young and middle-aged adults with a systolic BP response to standing greater than 6.5 mm Hg had almost double the risk of major adverse cardiovascular events (MACE) during follow-up, compared with other participants.

An exaggerated BP response remained an independent predictor of MACE, even after adjusting for traditional risk factors, including 24-hour BP (hazard ratio, 1.94; 95% confidence interval, 1.10 to 3.44), the study showed.

“The clinical implication is important, because now doctors measure blood pressure in young people in the upright posture, but what we say is it must be measured also while standing,” said Paolo Palatini, MD, a professor of internal medicine at the University of Padova, Italy, who led the study.

Previous studies have found that an exaggerated BP response to standing is a predictor of future hypertension, CV events, and mortality, particularly in older patients, but few prognostic data exist in those who are young to middle age, he noted.

The study, published in Hypertension, included 1,207 participants ages 18-45 years with untreated stage 1 hypertension (systolic BP 140-159 mm Hg or diastolic BP 90-100 mm Hg) in the prospective multicenter HARVEST study that began in Italy in 1990. The average age at enrollment was 33 years.

BP was measured at two visits 2 weeks apart, with each visit including three supine measurements taken after the patient had lain down for a minimum of 5 minutes, followed by three standing measurements taken 1 minute apart.

Based on the average of standing-lying BP differences during the two visits, participants were then classified as having a normal or exaggerated (top decile, lower limit > 6.5 mm Hg) systolic BP response to standing.

The 120 participants classified as “hyper-reactors” averaged an 11.4 mm Hg systolic BP increase upon standing, whereas the rest of the participants averaged a 3.8 mm Hg fall in systolic BP upon standing.

At their initial visit, hyper-reactors were more likely to be smokers (32.1% vs. 19.9%) and coffee drinkers (81.7% vs. 73%) and to have ambulatory hypertension (90.8% vs. 76.4%).

They were, however, no more likely to have a family history of cardiovascular events and had a lower supine systolic BP (140.5 mm Hg vs. 146.0 mm Hg), lower total cholesterol (4.93 mmol/L vs. 5.13 mmol/L), and higher HDL cholesterol (1.42 mmol/L vs. 1.35 mmol/L).

Age, sex, and body mass index were similar between the two groups, as was BP variability, nocturnal BP dip, and the frequency of extreme dippers. Participants with a normal systolic BP response were more likely to be treated for hypertension during follow-up (81.7% vs. 69.7%; P = .003).

In 630 participants who had catecholamines measured from 24-hour urine samples, the epinephrine/creatinine ratio was higher in hyper-reactors than normal responders (118.4 nmol/mol vs. 77.0 nmol/mol; P = .005).

During a median follow-up of 17.3 years, there were 105 major cardiovascular events, broadly defined to include acute coronary syndromes (48), any stroke (13), heart failure requiring hospitalization (3), aortic aneurysms (3), peripheral vascular disease (6), chronic kidney disease (12), and permanent atrial fibrillation (20).

The near doubling of MACE risk among hyper-reactors remained when atrial fibrillation was excluded and when 24-hour ambulatory systolic BP was included in the model, the author reported.

The results are in line with previous studies, indicating that hyper-reactors to standing have normal sympathetic activity at rest but an increased sympathetic response to stressors, observed Dr. Palatini and colleagues. This neurohumoral overshoot seems to be peculiar to young adults, whereas vascular stiffness seems to be the driving mechanism of orthostatic hypertension in older adults.

If a young person’s BP spikes upon standing, “then you have to treat them according to the average of the lying and the standing pressure,” Dr. Palatini said. “In these people, blood pressure should be treated earlier than in the past.”

“The study is important because it identified a new marker for hypertension that is easily evaluated in clinical practice,” Nieca Goldberg, MD, medical director of the Atria Institute, New York, and an associate professor of medicine at New York University Grossman School of Medicine, commented via email.

She noted that standing blood pressures are usually not taken as part of a medical visit and, in fact, seated blood pressures are often taken incorrectly while the patient is seated on the exam table rather than with their feet on the floor and using the proper cuff size.

“By incorporating standing BP, we will improve our diagnosis for hypertension, and with interventions such as diet and exercise, salt reduction, and medication when indicated, lower risk for heart attack, stroke, heart failure, [and] kidney and eye disease,” said Dr. Goldberg, who is also a spokesperson for the American Heart Association.

“The biggest barrier is that office visits are limited to 15 minutes, and not enough time is spent on the vital signs,” she noted. “We need changes to the health care system that value our ability to diagnose BP and take the time to counsel patients and explain treatment options.”

Limitations of the present study are that 72.7% of participants were men and all were White, Dr. Palatini said. Future work is also needed to create a uniform definition of BP hyper-reactivity to standing, possibly based on risk estimates, for inclusion in future hypertension guidelines.

The study was funded by the Association 18 Maggio 1370 in Italy. The authors have disclosed no relevant financial relationships. Dr. Goldberg reported being a spokesperson for the American Heart Association.

A version of this article first appeared on Medscape.com.

A sudden drop in blood pressure when standing is a common and concerning problem in elderly hypertensive people. Now, research suggests a large BP swing in the opposite direction on standing may be equally concerning in younger hypertensive people.

Young and middle-aged adults with a systolic BP response to standing greater than 6.5 mm Hg had almost double the risk of major adverse cardiovascular events (MACE) during follow-up, compared with other participants.

An exaggerated BP response remained an independent predictor of MACE, even after adjusting for traditional risk factors, including 24-hour BP (hazard ratio, 1.94; 95% confidence interval, 1.10 to 3.44), the study showed.

“The clinical implication is important, because now doctors measure blood pressure in young people in the upright posture, but what we say is it must be measured also while standing,” said Paolo Palatini, MD, a professor of internal medicine at the University of Padova, Italy, who led the study.

Previous studies have found that an exaggerated BP response to standing is a predictor of future hypertension, CV events, and mortality, particularly in older patients, but few prognostic data exist in those who are young to middle age, he noted.

The study, published in Hypertension, included 1,207 participants ages 18-45 years with untreated stage 1 hypertension (systolic BP 140-159 mm Hg or diastolic BP 90-100 mm Hg) in the prospective multicenter HARVEST study that began in Italy in 1990. The average age at enrollment was 33 years.

BP was measured at two visits 2 weeks apart, with each visit including three supine measurements taken after the patient had lain down for a minimum of 5 minutes, followed by three standing measurements taken 1 minute apart.

Based on the average of standing-lying BP differences during the two visits, participants were then classified as having a normal or exaggerated (top decile, lower limit > 6.5 mm Hg) systolic BP response to standing.

The 120 participants classified as “hyper-reactors” averaged an 11.4 mm Hg systolic BP increase upon standing, whereas the rest of the participants averaged a 3.8 mm Hg fall in systolic BP upon standing.

At their initial visit, hyper-reactors were more likely to be smokers (32.1% vs. 19.9%) and coffee drinkers (81.7% vs. 73%) and to have ambulatory hypertension (90.8% vs. 76.4%).

They were, however, no more likely to have a family history of cardiovascular events and had a lower supine systolic BP (140.5 mm Hg vs. 146.0 mm Hg), lower total cholesterol (4.93 mmol/L vs. 5.13 mmol/L), and higher HDL cholesterol (1.42 mmol/L vs. 1.35 mmol/L).

Age, sex, and body mass index were similar between the two groups, as was BP variability, nocturnal BP dip, and the frequency of extreme dippers. Participants with a normal systolic BP response were more likely to be treated for hypertension during follow-up (81.7% vs. 69.7%; P = .003).

In 630 participants who had catecholamines measured from 24-hour urine samples, the epinephrine/creatinine ratio was higher in hyper-reactors than normal responders (118.4 nmol/mol vs. 77.0 nmol/mol; P = .005).

During a median follow-up of 17.3 years, there were 105 major cardiovascular events, broadly defined to include acute coronary syndromes (48), any stroke (13), heart failure requiring hospitalization (3), aortic aneurysms (3), peripheral vascular disease (6), chronic kidney disease (12), and permanent atrial fibrillation (20).

The near doubling of MACE risk among hyper-reactors remained when atrial fibrillation was excluded and when 24-hour ambulatory systolic BP was included in the model, the author reported.

The results are in line with previous studies, indicating that hyper-reactors to standing have normal sympathetic activity at rest but an increased sympathetic response to stressors, observed Dr. Palatini and colleagues. This neurohumoral overshoot seems to be peculiar to young adults, whereas vascular stiffness seems to be the driving mechanism of orthostatic hypertension in older adults.

If a young person’s BP spikes upon standing, “then you have to treat them according to the average of the lying and the standing pressure,” Dr. Palatini said. “In these people, blood pressure should be treated earlier than in the past.”

“The study is important because it identified a new marker for hypertension that is easily evaluated in clinical practice,” Nieca Goldberg, MD, medical director of the Atria Institute, New York, and an associate professor of medicine at New York University Grossman School of Medicine, commented via email.

She noted that standing blood pressures are usually not taken as part of a medical visit and, in fact, seated blood pressures are often taken incorrectly while the patient is seated on the exam table rather than with their feet on the floor and using the proper cuff size.

“By incorporating standing BP, we will improve our diagnosis for hypertension, and with interventions such as diet and exercise, salt reduction, and medication when indicated, lower risk for heart attack, stroke, heart failure, [and] kidney and eye disease,” said Dr. Goldberg, who is also a spokesperson for the American Heart Association.

“The biggest barrier is that office visits are limited to 15 minutes, and not enough time is spent on the vital signs,” she noted. “We need changes to the health care system that value our ability to diagnose BP and take the time to counsel patients and explain treatment options.”

Limitations of the present study are that 72.7% of participants were men and all were White, Dr. Palatini said. Future work is also needed to create a uniform definition of BP hyper-reactivity to standing, possibly based on risk estimates, for inclusion in future hypertension guidelines.

The study was funded by the Association 18 Maggio 1370 in Italy. The authors have disclosed no relevant financial relationships. Dr. Goldberg reported being a spokesperson for the American Heart Association.

A version of this article first appeared on Medscape.com.

A sudden drop in blood pressure when standing is a common and concerning problem in elderly hypertensive people. Now, research suggests a large BP swing in the opposite direction on standing may be equally concerning in younger hypertensive people.

Young and middle-aged adults with a systolic BP response to standing greater than 6.5 mm Hg had almost double the risk of major adverse cardiovascular events (MACE) during follow-up, compared with other participants.

An exaggerated BP response remained an independent predictor of MACE, even after adjusting for traditional risk factors, including 24-hour BP (hazard ratio, 1.94; 95% confidence interval, 1.10 to 3.44), the study showed.

“The clinical implication is important, because now doctors measure blood pressure in young people in the upright posture, but what we say is it must be measured also while standing,” said Paolo Palatini, MD, a professor of internal medicine at the University of Padova, Italy, who led the study.

Previous studies have found that an exaggerated BP response to standing is a predictor of future hypertension, CV events, and mortality, particularly in older patients, but few prognostic data exist in those who are young to middle age, he noted.

The study, published in Hypertension, included 1,207 participants ages 18-45 years with untreated stage 1 hypertension (systolic BP 140-159 mm Hg or diastolic BP 90-100 mm Hg) in the prospective multicenter HARVEST study that began in Italy in 1990. The average age at enrollment was 33 years.

BP was measured at two visits 2 weeks apart, with each visit including three supine measurements taken after the patient had lain down for a minimum of 5 minutes, followed by three standing measurements taken 1 minute apart.

Based on the average of standing-lying BP differences during the two visits, participants were then classified as having a normal or exaggerated (top decile, lower limit > 6.5 mm Hg) systolic BP response to standing.

The 120 participants classified as “hyper-reactors” averaged an 11.4 mm Hg systolic BP increase upon standing, whereas the rest of the participants averaged a 3.8 mm Hg fall in systolic BP upon standing.

At their initial visit, hyper-reactors were more likely to be smokers (32.1% vs. 19.9%) and coffee drinkers (81.7% vs. 73%) and to have ambulatory hypertension (90.8% vs. 76.4%).

They were, however, no more likely to have a family history of cardiovascular events and had a lower supine systolic BP (140.5 mm Hg vs. 146.0 mm Hg), lower total cholesterol (4.93 mmol/L vs. 5.13 mmol/L), and higher HDL cholesterol (1.42 mmol/L vs. 1.35 mmol/L).

Age, sex, and body mass index were similar between the two groups, as was BP variability, nocturnal BP dip, and the frequency of extreme dippers. Participants with a normal systolic BP response were more likely to be treated for hypertension during follow-up (81.7% vs. 69.7%; P = .003).

In 630 participants who had catecholamines measured from 24-hour urine samples, the epinephrine/creatinine ratio was higher in hyper-reactors than normal responders (118.4 nmol/mol vs. 77.0 nmol/mol; P = .005).

During a median follow-up of 17.3 years, there were 105 major cardiovascular events, broadly defined to include acute coronary syndromes (48), any stroke (13), heart failure requiring hospitalization (3), aortic aneurysms (3), peripheral vascular disease (6), chronic kidney disease (12), and permanent atrial fibrillation (20).

The near doubling of MACE risk among hyper-reactors remained when atrial fibrillation was excluded and when 24-hour ambulatory systolic BP was included in the model, the author reported.

The results are in line with previous studies, indicating that hyper-reactors to standing have normal sympathetic activity at rest but an increased sympathetic response to stressors, observed Dr. Palatini and colleagues. This neurohumoral overshoot seems to be peculiar to young adults, whereas vascular stiffness seems to be the driving mechanism of orthostatic hypertension in older adults.

If a young person’s BP spikes upon standing, “then you have to treat them according to the average of the lying and the standing pressure,” Dr. Palatini said. “In these people, blood pressure should be treated earlier than in the past.”

“The study is important because it identified a new marker for hypertension that is easily evaluated in clinical practice,” Nieca Goldberg, MD, medical director of the Atria Institute, New York, and an associate professor of medicine at New York University Grossman School of Medicine, commented via email.

She noted that standing blood pressures are usually not taken as part of a medical visit and, in fact, seated blood pressures are often taken incorrectly while the patient is seated on the exam table rather than with their feet on the floor and using the proper cuff size.

“By incorporating standing BP, we will improve our diagnosis for hypertension, and with interventions such as diet and exercise, salt reduction, and medication when indicated, lower risk for heart attack, stroke, heart failure, [and] kidney and eye disease,” said Dr. Goldberg, who is also a spokesperson for the American Heart Association.

“The biggest barrier is that office visits are limited to 15 minutes, and not enough time is spent on the vital signs,” she noted. “We need changes to the health care system that value our ability to diagnose BP and take the time to counsel patients and explain treatment options.”

Limitations of the present study are that 72.7% of participants were men and all were White, Dr. Palatini said. Future work is also needed to create a uniform definition of BP hyper-reactivity to standing, possibly based on risk estimates, for inclusion in future hypertension guidelines.

The study was funded by the Association 18 Maggio 1370 in Italy. The authors have disclosed no relevant financial relationships. Dr. Goldberg reported being a spokesperson for the American Heart Association.

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.

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.

A new study has drawn attention to inaccurate measurement of LDL-cholesterol levels in some patients with current assays, which could lead to incorrect therapeutic approaches.

The patient groups most affected are those with high levels of the lipoprotein Lp(a), in whom LDL-cholesterol levels are being overestimated in current laboratory tests, the authors say.

“Current laboratory assays all have the limitation that they cannot measure or report LDL cholesterol accurately. They are actually measuring the combination of LDL and Lp(a),” senior study author Sotirios Tsimikas, MD, University of California, San Diego, explained to this news organization.

“Lp(a) can be lowered a little with niacin and PCSK9 inhibitors, but both have a quite a weak effect, and statins increase Lp(a). However, there are now multiple RNA-based therapeutics specifically targeting Lp(a) in clinical development,” he said.

At present, Lp(a) cholesterol has to be mathematically estimated, most commonly with the Dahlén formula, because of the lack of a validated, quantitative method to measure Lp(a) cholesterol, Dr. Tsimikas says.  

For the current study, the researchers used a novel, quantitative, sensitive method to directly measure Lp(a) cholesterol, then applied this method to data from a recent study with the one of the new Lp(a)-lowering drugs in development – pelacarsen – which was conducted in patients with elevated Lp(a) levels.

Results showed that direct Lp(a)-cholesterol assessment, and subtracting this value from the laboratory LDL-cholesterol value, provides a more accurate reflection of the baseline and change in LDL cholesterol, the authors report. In the current study, corrected LDL cholesterol was 13 to 16 mg/dL lower than laboratory-reported LDL cholesterol.

Using the corrected LDL-cholesterol results, the study showed that pelacarsen significantly decreases Lp(a) cholesterol, with neutral to modest effects on LDL.

The study also suggests that the current method of calculating Lp(a) cholesterol, and then deriving a corrected LDL cholesterol – the Dahlén formula – is not accurate. 

“The Dahlén formula relies on the assumption that Lp(a) cholesterol is universally a fixed 30% of Lp(a) mass, but this usually isn’t the case. The Dahlén formula needs to be discontinued. It can be highly inaccurate,” Dr. Tsimikas said.  

Important implications

In an accompanying editorial, Guillaume Paré, MD, Michael Chong, PhD student, and Pedrum Mohammadi-Shemirani, BSc, all of McMaster University, Hamilton, Ont., say the current findings have three important clinical implications.

“First, they provide further proof that in individuals with elevated Lp(a), the contribution of Lp(a)-cholesterol to LDL-cholesterol is non-negligible using standard assays, with 13-16 mg/dL lower LDL-cholesterol post-correction.”

Secondly, the editorialists point out that these new findings confirm that the effect of Lp(a) inhibitors is likely to be mostly confined to Lp(a), “as would be expected.”

Finally, “and perhaps more importantly, the authors highlight the need to improve clinical reporting of lipid fractions to properly treat LDL-cholesterol and Lp(a) in high-risk patients,” they note.

“The report paves the way for future studies investigating the clinical utility of these additional measurements to initiate and monitor lipid-lowering therapy,” they conclude.

The clinical trial was funded by Ionis Pharmaceuticals, and the direct Lp(a)-cholesterol measurements were funded by Novartis through a research grant to the University of California, San Diego. Dr. Tsimikas is an employee of Ionis Pharmaceuticals and of the University of California, San Diego, and he is a cofounder of Covicept Therapeutics. He is also a coinventor and receives royalties from patents owned by UCSD on oxidation-specific antibodies and on biomarkers related to oxidized lipoproteins, as well as a cofounder and has equity interest in Oxitope and Kleanthi Diagnostics.

A version of this article first appeared on Medscape.com.

A new study has drawn attention to inaccurate measurement of LDL-cholesterol levels in some patients with current assays, which could lead to incorrect therapeutic approaches.

The patient groups most affected are those with high levels of the lipoprotein Lp(a), in whom LDL-cholesterol levels are being overestimated in current laboratory tests, the authors say.

“Current laboratory assays all have the limitation that they cannot measure or report LDL cholesterol accurately. They are actually measuring the combination of LDL and Lp(a),” senior study author Sotirios Tsimikas, MD, University of California, San Diego, explained to this news organization.

“Lp(a) can be lowered a little with niacin and PCSK9 inhibitors, but both have a quite a weak effect, and statins increase Lp(a). However, there are now multiple RNA-based therapeutics specifically targeting Lp(a) in clinical development,” he said.

At present, Lp(a) cholesterol has to be mathematically estimated, most commonly with the Dahlén formula, because of the lack of a validated, quantitative method to measure Lp(a) cholesterol, Dr. Tsimikas says.  

For the current study, the researchers used a novel, quantitative, sensitive method to directly measure Lp(a) cholesterol, then applied this method to data from a recent study with the one of the new Lp(a)-lowering drugs in development – pelacarsen – which was conducted in patients with elevated Lp(a) levels.

Results showed that direct Lp(a)-cholesterol assessment, and subtracting this value from the laboratory LDL-cholesterol value, provides a more accurate reflection of the baseline and change in LDL cholesterol, the authors report. In the current study, corrected LDL cholesterol was 13 to 16 mg/dL lower than laboratory-reported LDL cholesterol.

Using the corrected LDL-cholesterol results, the study showed that pelacarsen significantly decreases Lp(a) cholesterol, with neutral to modest effects on LDL.

The study also suggests that the current method of calculating Lp(a) cholesterol, and then deriving a corrected LDL cholesterol – the Dahlén formula – is not accurate. 

“The Dahlén formula relies on the assumption that Lp(a) cholesterol is universally a fixed 30% of Lp(a) mass, but this usually isn’t the case. The Dahlén formula needs to be discontinued. It can be highly inaccurate,” Dr. Tsimikas said.  

Important implications

In an accompanying editorial, Guillaume Paré, MD, Michael Chong, PhD student, and Pedrum Mohammadi-Shemirani, BSc, all of McMaster University, Hamilton, Ont., say the current findings have three important clinical implications.

“First, they provide further proof that in individuals with elevated Lp(a), the contribution of Lp(a)-cholesterol to LDL-cholesterol is non-negligible using standard assays, with 13-16 mg/dL lower LDL-cholesterol post-correction.”

Secondly, the editorialists point out that these new findings confirm that the effect of Lp(a) inhibitors is likely to be mostly confined to Lp(a), “as would be expected.”

Finally, “and perhaps more importantly, the authors highlight the need to improve clinical reporting of lipid fractions to properly treat LDL-cholesterol and Lp(a) in high-risk patients,” they note.

“The report paves the way for future studies investigating the clinical utility of these additional measurements to initiate and monitor lipid-lowering therapy,” they conclude.

The clinical trial was funded by Ionis Pharmaceuticals, and the direct Lp(a)-cholesterol measurements were funded by Novartis through a research grant to the University of California, San Diego. Dr. Tsimikas is an employee of Ionis Pharmaceuticals and of the University of California, San Diego, and he is a cofounder of Covicept Therapeutics. He is also a coinventor and receives royalties from patents owned by UCSD on oxidation-specific antibodies and on biomarkers related to oxidized lipoproteins, as well as a cofounder and has equity interest in Oxitope and Kleanthi Diagnostics.

A version of this article first appeared on Medscape.com.

A new study has drawn attention to inaccurate measurement of LDL-cholesterol levels in some patients with current assays, which could lead to incorrect therapeutic approaches.

The patient groups most affected are those with high levels of the lipoprotein Lp(a), in whom LDL-cholesterol levels are being overestimated in current laboratory tests, the authors say.

“Current laboratory assays all have the limitation that they cannot measure or report LDL cholesterol accurately. They are actually measuring the combination of LDL and Lp(a),” senior study author Sotirios Tsimikas, MD, University of California, San Diego, explained to this news organization.

“Lp(a) can be lowered a little with niacin and PCSK9 inhibitors, but both have a quite a weak effect, and statins increase Lp(a). However, there are now multiple RNA-based therapeutics specifically targeting Lp(a) in clinical development,” he said.

At present, Lp(a) cholesterol has to be mathematically estimated, most commonly with the Dahlén formula, because of the lack of a validated, quantitative method to measure Lp(a) cholesterol, Dr. Tsimikas says.  

For the current study, the researchers used a novel, quantitative, sensitive method to directly measure Lp(a) cholesterol, then applied this method to data from a recent study with the one of the new Lp(a)-lowering drugs in development – pelacarsen – which was conducted in patients with elevated Lp(a) levels.

Results showed that direct Lp(a)-cholesterol assessment, and subtracting this value from the laboratory LDL-cholesterol value, provides a more accurate reflection of the baseline and change in LDL cholesterol, the authors report. In the current study, corrected LDL cholesterol was 13 to 16 mg/dL lower than laboratory-reported LDL cholesterol.

Using the corrected LDL-cholesterol results, the study showed that pelacarsen significantly decreases Lp(a) cholesterol, with neutral to modest effects on LDL.

The study also suggests that the current method of calculating Lp(a) cholesterol, and then deriving a corrected LDL cholesterol – the Dahlén formula – is not accurate. 

“The Dahlén formula relies on the assumption that Lp(a) cholesterol is universally a fixed 30% of Lp(a) mass, but this usually isn’t the case. The Dahlén formula needs to be discontinued. It can be highly inaccurate,” Dr. Tsimikas said.  

Important implications

In an accompanying editorial, Guillaume Paré, MD, Michael Chong, PhD student, and Pedrum Mohammadi-Shemirani, BSc, all of McMaster University, Hamilton, Ont., say the current findings have three important clinical implications.

“First, they provide further proof that in individuals with elevated Lp(a), the contribution of Lp(a)-cholesterol to LDL-cholesterol is non-negligible using standard assays, with 13-16 mg/dL lower LDL-cholesterol post-correction.”

Secondly, the editorialists point out that these new findings confirm that the effect of Lp(a) inhibitors is likely to be mostly confined to Lp(a), “as would be expected.”

Finally, “and perhaps more importantly, the authors highlight the need to improve clinical reporting of lipid fractions to properly treat LDL-cholesterol and Lp(a) in high-risk patients,” they note.

“The report paves the way for future studies investigating the clinical utility of these additional measurements to initiate and monitor lipid-lowering therapy,” they conclude.

The clinical trial was funded by Ionis Pharmaceuticals, and the direct Lp(a)-cholesterol measurements were funded by Novartis through a research grant to the University of California, San Diego. Dr. Tsimikas is an employee of Ionis Pharmaceuticals and of the University of California, San Diego, and he is a cofounder of Covicept Therapeutics. He is also a coinventor and receives royalties from patents owned by UCSD on oxidation-specific antibodies and on biomarkers related to oxidized lipoproteins, as well as a cofounder and has equity interest in Oxitope and Kleanthi Diagnostics.

A version of this article first appeared on Medscape.com.

Doctors’ opinions about whether to treat women with osteoporosis with hormone therapy vary. Guidelines by medical societies including those of the American College of Physicians, on the other hand, generally do not recommend it as a first line therapy for the disease, at least in part due to the risks associated with taking it.

This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.

According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.

Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
 

Women’s Health Initiative findings

The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.

The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.

Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.

“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
 

Hormone therapy’s complex history

HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.

While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.

Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.

“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”

Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.

It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
 

Today’s use of HT in women with osteoporosis

Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.

“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.

“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.

“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.

Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.

“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.

According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.

“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
 

Additional scenarios when doctors may advise HT

“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.

“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”

Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.

“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”

“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.

“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”

Dr. Roberts added that HT would be more of a niche drug.

“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”

Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other  experts interviewed for this piece reported no conflicts.

Doctors’ opinions about whether to treat women with osteoporosis with hormone therapy vary. Guidelines by medical societies including those of the American College of Physicians, on the other hand, generally do not recommend it as a first line therapy for the disease, at least in part due to the risks associated with taking it.

This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.

According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.

Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
 

Women’s Health Initiative findings

The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.

The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.

Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.

“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
 

Hormone therapy’s complex history

HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.

While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.

Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.

“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”

Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.

It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
 

Today’s use of HT in women with osteoporosis

Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.

“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.

“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.

“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.

Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.

“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.

According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.

“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
 

Additional scenarios when doctors may advise HT

“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.

“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”

Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.

“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”

“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.

“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”

Dr. Roberts added that HT would be more of a niche drug.

“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”

Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other  experts interviewed for this piece reported no conflicts.

Doctors’ opinions about whether to treat women with osteoporosis with hormone therapy vary. Guidelines by medical societies including those of the American College of Physicians, on the other hand, generally do not recommend it as a first line therapy for the disease, at least in part due to the risks associated with taking it.

This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.

According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.

Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
 

Women’s Health Initiative findings

The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.

The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.

Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.

“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
 

Hormone therapy’s complex history

HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.

While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.

Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.

“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”

Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.

It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
 

Today’s use of HT in women with osteoporosis

Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.

“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.

“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.

“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.

Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.

“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.

According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.

“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
 

Additional scenarios when doctors may advise HT

“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.

“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”

Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.

“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”

“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.

“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”

Dr. Roberts added that HT would be more of a niche drug.

“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”

Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other  experts interviewed for this piece reported no conflicts.

The American College of Cardiology has issued an expert consensus clinical guidance document for the evaluation and management of adults with key cardiovascular consequences of COVID-19.

The document makes recommendations on how to evaluate and manage COVID-associated myocarditis and long COVID and gives advice on resumption of exercise following COVID-19 infection.

The clinical guidance was published online March 16 in the Journal of the American College of Cardiology.

AlexLMX/Getty Images

“The best means to diagnose and treat myocarditis and long COVID following SARS-CoV-2 infection continues to evolve,” said Ty Gluckman, MD, MHA, cochair of the expert consensus decision pathway. “This document attempts to provide key recommendations for how to evaluate and manage adults with these conditions, including guidance for safe return to play for both competitive and noncompetitive athletes.”

The authors of the guidance note that COVID-19 can be associated with various abnormalities in cardiac testing and a wide range of cardiovascular complications. For some patients, cardiac symptoms such as chest pain, shortness of breath, fatigue, and palpitations persist, lasting months after the initial illness, and evidence of myocardial injury has also been observed in both symptomatic and asymptomatic individuals, as well as after receipt of the COVID-19 mRNA vaccine. 

“For clinicians treating these individuals, a growing number of questions exist related to evaluation and management of these conditions, as well as safe resumption of physical activity,” they say. This report is intended to provide practical guidance on these issues.
 

Myocarditis

The report states that myocarditis has been recognized as a rare but serious complication of SARS-CoV-2 infection as well as COVID-19 mRNA vaccination.

It defines myocarditis as: 1.cardiac symptoms such as chest pain, dyspnea, palpitations, or syncope; 2. elevated cardiac troponin; and 3. abnormal electrocardiographic, echocardiographic, cardiac MRI, and/or histopathologic findings on biopsy.

The document makes the following recommendations in regard to COVID-related myocarditis:

When there is increased suspicion for cardiac involvement with COVID-19, initial testing should consist of an ECG, measurement of cardiac troponin, and an echocardiogram. Cardiology consultation is recommended for those with a rising cardiac troponin and/or echocardiographic abnormalities. Cardiac MRI is recommended in hemodynamically stable patients with suspected myocarditis.

Hospitalization is recommended for patients with definite myocarditis, ideally at an advanced heart failure center. Patients with fulminant myocarditis should be managed at centers with an expertise in advanced heart failure, mechanical circulatory support, and other advanced therapies.

Patients with myocarditis and COVID-19 pneumonia (with an ongoing need for supplemental oxygen) should be treated with corticosteroids. For patients with suspected pericardial involvement, treatment with NSAIDs, colchicine, and/or prednisone is reasonable. Intravenous corticosteroids may be considered in those with suspected or confirmed COVID-19 myocarditis with hemodynamic compromise or MIS-A (multisystem inflammatory syndrome in adults). Empiric use of corticosteroids may also be considered in those with biopsy evidence of severe myocardial infiltrates or fulminant myocarditis, balanced against infection risk.

As appropriate, guideline-directed medical therapy for heart failure should be initiated and continued after discharge.

The document notes that myocarditis following COVID-19 mRNA vaccination is rare, with highest rates seen in young males after the second vaccine dose. As of May 22, 2021, the U.S. Vaccine Adverse Event Reporting System noted rates of 40.6 cases per million after the second vaccine dose among male individuals aged 12-29 years and 2.4 cases per million among male individuals aged 30 and older. Corresponding rates in female individuals were 4.2 and 1 cases per million, respectively.

But the report says that COVID-19 vaccination is associated with “a very favorable benefit-to-risk ratio” for all age and sex groups evaluated thus far.

In general, vaccine-associated myocarditis should be diagnosed, categorized, and treated in a manner analogous to myocarditis following SARS-CoV-2 infection, the guidance advises.
 

Long COVID

The document refers to long COVID as postacute sequelae of SARS-CoV-2 infection (PASC), and reports that this condition is experienced by up to 10%-30% of infected individuals. It is defined by a constellation of new, returning, or persistent health problems experienced by individuals 4 or more weeks after COVID-19 infection.

Although individuals with this condition may experience wide-ranging symptoms, the symptoms that draw increased attention to the cardiovascular system include tachycardia, exercise intolerance, chest pain, and shortness of breath.

Nicole Bhave, MD, cochair of the expert consensus decision pathway, says: “There appears to be a ‘downward spiral’ for long-COVID patients. Fatigue and decreased exercise capacity lead to diminished activity and bed rest, in turn leading to worsening symptoms and decreased quality of life.” She adds that “the writing committee recommends a basic cardiopulmonary evaluation performed up front to determine if further specialty care and formalized medical therapy is needed for these patients.”

The authors propose two terms to better understand potential etiologies for those with cardiovascular symptoms:

PASC-CVD, or PASC-cardiovascular disease, refers to a broad group of cardiovascular conditions (including myocarditis) that manifest at least 4 weeks after COVID-19 infection.

PASC-CVS, or PASC-cardiovascular syndrome, includes a wide range of cardiovascular symptoms without objective evidence of cardiovascular disease following standard diagnostic testing.

The document makes the following recommendations for the management of PASC-CVD and PASC-CVS.

For patients with cardiovascular symptoms and suspected PASC, the authors suggest that a reasonable initial testing approach includes basic laboratory testing, including cardiac troponin, an ECG, an echocardiogram, an ambulatory rhythm monitor, chest imaging, and/or pulmonary function tests.

Cardiology consultation is recommended for patients with PASC who have abnormal cardiac test results, known cardiovascular disease with new or worsening symptoms, documented cardiac complications during SARS-CoV-2 infection, and/or persistent cardiopulmonary symptoms that are not otherwise explained.

Recumbent or semirecumbent exercise (for example, rowing, swimming, or cycling) is recommended initially for PASC-CVS patients with tachycardia, exercise/orthostatic intolerance, and/or deconditioning, with transition to upright exercise as orthostatic intolerance improves. Exercise duration should also be short (5-10 minutes/day) initially, with gradual increases as functional capacity improves.

Salt and fluid loading represent nonpharmacologic interventions that may provide symptomatic relief for patients with tachycardia, palpitations, and/or orthostatic hypotension.

Beta-blockers, nondihydropyridine calcium-channel blockers, ivabradine, fludrocortisone, and midodrine may be used empirically as well.
 

Return to play for athletes

The authors note that concerns about possible cardiac injury after COVID-19 fueled early apprehension regarding the safety of competitive sports for athletes recovering from the infection.

But they say that subsequent data from large registries have demonstrated an overall low prevalence of clinical myocarditis, without a rise in the rate of adverse cardiac events. Based on this, updated guidance is provided with a practical, evidence-based framework to guide resumption of athletics and intense exercise training.

They make the following recommendations:

• For athletes recovering from COVID-19 with ongoing cardiopulmonary symptoms (chest pain, shortness of breath, palpitations, lightheadedness) or those requiring hospitalization with increased suspicion for cardiac involvement, further evaluation with triad testing – an ECG, measurement of cardiac troponin, and an echocardiogram – should be performed.
• For those with abnormal test results, further evaluation with cardiac MRI should be considered. Individuals diagnosed with clinical myocarditis should abstain from exercise for 3-6 months.
• Cardiac testing is not recommended for asymptomatic individuals following COVID-19 infection. Individuals should abstain from training for 3 days to ensure that symptoms do not develop.
• For those with mild or moderate noncardiopulmonary symptoms (fever, lethargy, muscle aches), training may resume after symptom resolution.
• For those with remote infection (≥3 months) without ongoing cardiopulmonary symptoms, a gradual increase in exercise is recommended without the need for cardiac testing.

Based on the low prevalence of myocarditis observed in competitive athletes with COVID-19, the authors note that these recommendations can be reasonably applied to high-school athletes (aged 14 and older) along with adult recreational exercise enthusiasts.

Future study is needed, however, to better understand how long cardiac abnormalities persist following COVID-19 infection and the role of exercise training in long COVID.

The authors conclude that the current guidance is intended to help clinicians understand not only when testing may be warranted, but also when it is not.

“Given that it reflects the current state of knowledge through early 2022, it is anticipated that recommendations will change over time as our understanding evolves,” they say.

The 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19: Myocarditis, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and Return to Play will be discussed in a session at the American College of Cardiology’s annual scientific session meeting in Washington in April.

A version of this article first appeared on Medscape.com.

The American College of Cardiology has issued an expert consensus clinical guidance document for the evaluation and management of adults with key cardiovascular consequences of COVID-19.

The document makes recommendations on how to evaluate and manage COVID-associated myocarditis and long COVID and gives advice on resumption of exercise following COVID-19 infection.

The clinical guidance was published online March 16 in the Journal of the American College of Cardiology.

AlexLMX/Getty Images

“The best means to diagnose and treat myocarditis and long COVID following SARS-CoV-2 infection continues to evolve,” said Ty Gluckman, MD, MHA, cochair of the expert consensus decision pathway. “This document attempts to provide key recommendations for how to evaluate and manage adults with these conditions, including guidance for safe return to play for both competitive and noncompetitive athletes.”

The authors of the guidance note that COVID-19 can be associated with various abnormalities in cardiac testing and a wide range of cardiovascular complications. For some patients, cardiac symptoms such as chest pain, shortness of breath, fatigue, and palpitations persist, lasting months after the initial illness, and evidence of myocardial injury has also been observed in both symptomatic and asymptomatic individuals, as well as after receipt of the COVID-19 mRNA vaccine. 

“For clinicians treating these individuals, a growing number of questions exist related to evaluation and management of these conditions, as well as safe resumption of physical activity,” they say. This report is intended to provide practical guidance on these issues.
 

Myocarditis

The report states that myocarditis has been recognized as a rare but serious complication of SARS-CoV-2 infection as well as COVID-19 mRNA vaccination.

It defines myocarditis as: 1.cardiac symptoms such as chest pain, dyspnea, palpitations, or syncope; 2. elevated cardiac troponin; and 3. abnormal electrocardiographic, echocardiographic, cardiac MRI, and/or histopathologic findings on biopsy.

The document makes the following recommendations in regard to COVID-related myocarditis:

When there is increased suspicion for cardiac involvement with COVID-19, initial testing should consist of an ECG, measurement of cardiac troponin, and an echocardiogram. Cardiology consultation is recommended for those with a rising cardiac troponin and/or echocardiographic abnormalities. Cardiac MRI is recommended in hemodynamically stable patients with suspected myocarditis.

Hospitalization is recommended for patients with definite myocarditis, ideally at an advanced heart failure center. Patients with fulminant myocarditis should be managed at centers with an expertise in advanced heart failure, mechanical circulatory support, and other advanced therapies.

Patients with myocarditis and COVID-19 pneumonia (with an ongoing need for supplemental oxygen) should be treated with corticosteroids. For patients with suspected pericardial involvement, treatment with NSAIDs, colchicine, and/or prednisone is reasonable. Intravenous corticosteroids may be considered in those with suspected or confirmed COVID-19 myocarditis with hemodynamic compromise or MIS-A (multisystem inflammatory syndrome in adults). Empiric use of corticosteroids may also be considered in those with biopsy evidence of severe myocardial infiltrates or fulminant myocarditis, balanced against infection risk.

As appropriate, guideline-directed medical therapy for heart failure should be initiated and continued after discharge.

The document notes that myocarditis following COVID-19 mRNA vaccination is rare, with highest rates seen in young males after the second vaccine dose. As of May 22, 2021, the U.S. Vaccine Adverse Event Reporting System noted rates of 40.6 cases per million after the second vaccine dose among male individuals aged 12-29 years and 2.4 cases per million among male individuals aged 30 and older. Corresponding rates in female individuals were 4.2 and 1 cases per million, respectively.

But the report says that COVID-19 vaccination is associated with “a very favorable benefit-to-risk ratio” for all age and sex groups evaluated thus far.

In general, vaccine-associated myocarditis should be diagnosed, categorized, and treated in a manner analogous to myocarditis following SARS-CoV-2 infection, the guidance advises.
 

Long COVID

The document refers to long COVID as postacute sequelae of SARS-CoV-2 infection (PASC), and reports that this condition is experienced by up to 10%-30% of infected individuals. It is defined by a constellation of new, returning, or persistent health problems experienced by individuals 4 or more weeks after COVID-19 infection.

Although individuals with this condition may experience wide-ranging symptoms, the symptoms that draw increased attention to the cardiovascular system include tachycardia, exercise intolerance, chest pain, and shortness of breath.

Nicole Bhave, MD, cochair of the expert consensus decision pathway, says: “There appears to be a ‘downward spiral’ for long-COVID patients. Fatigue and decreased exercise capacity lead to diminished activity and bed rest, in turn leading to worsening symptoms and decreased quality of life.” She adds that “the writing committee recommends a basic cardiopulmonary evaluation performed up front to determine if further specialty care and formalized medical therapy is needed for these patients.”

The authors propose two terms to better understand potential etiologies for those with cardiovascular symptoms:

PASC-CVD, or PASC-cardiovascular disease, refers to a broad group of cardiovascular conditions (including myocarditis) that manifest at least 4 weeks after COVID-19 infection.

PASC-CVS, or PASC-cardiovascular syndrome, includes a wide range of cardiovascular symptoms without objective evidence of cardiovascular disease following standard diagnostic testing.

The document makes the following recommendations for the management of PASC-CVD and PASC-CVS.

For patients with cardiovascular symptoms and suspected PASC, the authors suggest that a reasonable initial testing approach includes basic laboratory testing, including cardiac troponin, an ECG, an echocardiogram, an ambulatory rhythm monitor, chest imaging, and/or pulmonary function tests.

Cardiology consultation is recommended for patients with PASC who have abnormal cardiac test results, known cardiovascular disease with new or worsening symptoms, documented cardiac complications during SARS-CoV-2 infection, and/or persistent cardiopulmonary symptoms that are not otherwise explained.

Recumbent or semirecumbent exercise (for example, rowing, swimming, or cycling) is recommended initially for PASC-CVS patients with tachycardia, exercise/orthostatic intolerance, and/or deconditioning, with transition to upright exercise as orthostatic intolerance improves. Exercise duration should also be short (5-10 minutes/day) initially, with gradual increases as functional capacity improves.

Salt and fluid loading represent nonpharmacologic interventions that may provide symptomatic relief for patients with tachycardia, palpitations, and/or orthostatic hypotension.

Beta-blockers, nondihydropyridine calcium-channel blockers, ivabradine, fludrocortisone, and midodrine may be used empirically as well.
 

Return to play for athletes

The authors note that concerns about possible cardiac injury after COVID-19 fueled early apprehension regarding the safety of competitive sports for athletes recovering from the infection.

But they say that subsequent data from large registries have demonstrated an overall low prevalence of clinical myocarditis, without a rise in the rate of adverse cardiac events. Based on this, updated guidance is provided with a practical, evidence-based framework to guide resumption of athletics and intense exercise training.

They make the following recommendations:

• For athletes recovering from COVID-19 with ongoing cardiopulmonary symptoms (chest pain, shortness of breath, palpitations, lightheadedness) or those requiring hospitalization with increased suspicion for cardiac involvement, further evaluation with triad testing – an ECG, measurement of cardiac troponin, and an echocardiogram – should be performed.
• For those with abnormal test results, further evaluation with cardiac MRI should be considered. Individuals diagnosed with clinical myocarditis should abstain from exercise for 3-6 months.
• Cardiac testing is not recommended for asymptomatic individuals following COVID-19 infection. Individuals should abstain from training for 3 days to ensure that symptoms do not develop.
• For those with mild or moderate noncardiopulmonary symptoms (fever, lethargy, muscle aches), training may resume after symptom resolution.
• For those with remote infection (≥3 months) without ongoing cardiopulmonary symptoms, a gradual increase in exercise is recommended without the need for cardiac testing.

Based on the low prevalence of myocarditis observed in competitive athletes with COVID-19, the authors note that these recommendations can be reasonably applied to high-school athletes (aged 14 and older) along with adult recreational exercise enthusiasts.

Future study is needed, however, to better understand how long cardiac abnormalities persist following COVID-19 infection and the role of exercise training in long COVID.

The authors conclude that the current guidance is intended to help clinicians understand not only when testing may be warranted, but also when it is not.

“Given that it reflects the current state of knowledge through early 2022, it is anticipated that recommendations will change over time as our understanding evolves,” they say.

The 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19: Myocarditis, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and Return to Play will be discussed in a session at the American College of Cardiology’s annual scientific session meeting in Washington in April.

A version of this article first appeared on Medscape.com.

The American College of Cardiology has issued an expert consensus clinical guidance document for the evaluation and management of adults with key cardiovascular consequences of COVID-19.

The document makes recommendations on how to evaluate and manage COVID-associated myocarditis and long COVID and gives advice on resumption of exercise following COVID-19 infection.

The clinical guidance was published online March 16 in the Journal of the American College of Cardiology.

AlexLMX/Getty Images

“The best means to diagnose and treat myocarditis and long COVID following SARS-CoV-2 infection continues to evolve,” said Ty Gluckman, MD, MHA, cochair of the expert consensus decision pathway. “This document attempts to provide key recommendations for how to evaluate and manage adults with these conditions, including guidance for safe return to play for both competitive and noncompetitive athletes.”

The authors of the guidance note that COVID-19 can be associated with various abnormalities in cardiac testing and a wide range of cardiovascular complications. For some patients, cardiac symptoms such as chest pain, shortness of breath, fatigue, and palpitations persist, lasting months after the initial illness, and evidence of myocardial injury has also been observed in both symptomatic and asymptomatic individuals, as well as after receipt of the COVID-19 mRNA vaccine. 

“For clinicians treating these individuals, a growing number of questions exist related to evaluation and management of these conditions, as well as safe resumption of physical activity,” they say. This report is intended to provide practical guidance on these issues.
 

Myocarditis

The report states that myocarditis has been recognized as a rare but serious complication of SARS-CoV-2 infection as well as COVID-19 mRNA vaccination.

It defines myocarditis as: 1.cardiac symptoms such as chest pain, dyspnea, palpitations, or syncope; 2. elevated cardiac troponin; and 3. abnormal electrocardiographic, echocardiographic, cardiac MRI, and/or histopathologic findings on biopsy.

The document makes the following recommendations in regard to COVID-related myocarditis:

When there is increased suspicion for cardiac involvement with COVID-19, initial testing should consist of an ECG, measurement of cardiac troponin, and an echocardiogram. Cardiology consultation is recommended for those with a rising cardiac troponin and/or echocardiographic abnormalities. Cardiac MRI is recommended in hemodynamically stable patients with suspected myocarditis.

Hospitalization is recommended for patients with definite myocarditis, ideally at an advanced heart failure center. Patients with fulminant myocarditis should be managed at centers with an expertise in advanced heart failure, mechanical circulatory support, and other advanced therapies.

Patients with myocarditis and COVID-19 pneumonia (with an ongoing need for supplemental oxygen) should be treated with corticosteroids. For patients with suspected pericardial involvement, treatment with NSAIDs, colchicine, and/or prednisone is reasonable. Intravenous corticosteroids may be considered in those with suspected or confirmed COVID-19 myocarditis with hemodynamic compromise or MIS-A (multisystem inflammatory syndrome in adults). Empiric use of corticosteroids may also be considered in those with biopsy evidence of severe myocardial infiltrates or fulminant myocarditis, balanced against infection risk.

As appropriate, guideline-directed medical therapy for heart failure should be initiated and continued after discharge.

The document notes that myocarditis following COVID-19 mRNA vaccination is rare, with highest rates seen in young males after the second vaccine dose. As of May 22, 2021, the U.S. Vaccine Adverse Event Reporting System noted rates of 40.6 cases per million after the second vaccine dose among male individuals aged 12-29 years and 2.4 cases per million among male individuals aged 30 and older. Corresponding rates in female individuals were 4.2 and 1 cases per million, respectively.

But the report says that COVID-19 vaccination is associated with “a very favorable benefit-to-risk ratio” for all age and sex groups evaluated thus far.

In general, vaccine-associated myocarditis should be diagnosed, categorized, and treated in a manner analogous to myocarditis following SARS-CoV-2 infection, the guidance advises.
 

Long COVID

The document refers to long COVID as postacute sequelae of SARS-CoV-2 infection (PASC), and reports that this condition is experienced by up to 10%-30% of infected individuals. It is defined by a constellation of new, returning, or persistent health problems experienced by individuals 4 or more weeks after COVID-19 infection.

Although individuals with this condition may experience wide-ranging symptoms, the symptoms that draw increased attention to the cardiovascular system include tachycardia, exercise intolerance, chest pain, and shortness of breath.

Nicole Bhave, MD, cochair of the expert consensus decision pathway, says: “There appears to be a ‘downward spiral’ for long-COVID patients. Fatigue and decreased exercise capacity lead to diminished activity and bed rest, in turn leading to worsening symptoms and decreased quality of life.” She adds that “the writing committee recommends a basic cardiopulmonary evaluation performed up front to determine if further specialty care and formalized medical therapy is needed for these patients.”

The authors propose two terms to better understand potential etiologies for those with cardiovascular symptoms:

PASC-CVD, or PASC-cardiovascular disease, refers to a broad group of cardiovascular conditions (including myocarditis) that manifest at least 4 weeks after COVID-19 infection.

PASC-CVS, or PASC-cardiovascular syndrome, includes a wide range of cardiovascular symptoms without objective evidence of cardiovascular disease following standard diagnostic testing.

The document makes the following recommendations for the management of PASC-CVD and PASC-CVS.

For patients with cardiovascular symptoms and suspected PASC, the authors suggest that a reasonable initial testing approach includes basic laboratory testing, including cardiac troponin, an ECG, an echocardiogram, an ambulatory rhythm monitor, chest imaging, and/or pulmonary function tests.

Cardiology consultation is recommended for patients with PASC who have abnormal cardiac test results, known cardiovascular disease with new or worsening symptoms, documented cardiac complications during SARS-CoV-2 infection, and/or persistent cardiopulmonary symptoms that are not otherwise explained.

Recumbent or semirecumbent exercise (for example, rowing, swimming, or cycling) is recommended initially for PASC-CVS patients with tachycardia, exercise/orthostatic intolerance, and/or deconditioning, with transition to upright exercise as orthostatic intolerance improves. Exercise duration should also be short (5-10 minutes/day) initially, with gradual increases as functional capacity improves.

Salt and fluid loading represent nonpharmacologic interventions that may provide symptomatic relief for patients with tachycardia, palpitations, and/or orthostatic hypotension.

Beta-blockers, nondihydropyridine calcium-channel blockers, ivabradine, fludrocortisone, and midodrine may be used empirically as well.
 

Return to play for athletes

The authors note that concerns about possible cardiac injury after COVID-19 fueled early apprehension regarding the safety of competitive sports for athletes recovering from the infection.

But they say that subsequent data from large registries have demonstrated an overall low prevalence of clinical myocarditis, without a rise in the rate of adverse cardiac events. Based on this, updated guidance is provided with a practical, evidence-based framework to guide resumption of athletics and intense exercise training.

They make the following recommendations:

• For athletes recovering from COVID-19 with ongoing cardiopulmonary symptoms (chest pain, shortness of breath, palpitations, lightheadedness) or those requiring hospitalization with increased suspicion for cardiac involvement, further evaluation with triad testing – an ECG, measurement of cardiac troponin, and an echocardiogram – should be performed.
• For those with abnormal test results, further evaluation with cardiac MRI should be considered. Individuals diagnosed with clinical myocarditis should abstain from exercise for 3-6 months.
• Cardiac testing is not recommended for asymptomatic individuals following COVID-19 infection. Individuals should abstain from training for 3 days to ensure that symptoms do not develop.
• For those with mild or moderate noncardiopulmonary symptoms (fever, lethargy, muscle aches), training may resume after symptom resolution.
• For those with remote infection (≥3 months) without ongoing cardiopulmonary symptoms, a gradual increase in exercise is recommended without the need for cardiac testing.

Based on the low prevalence of myocarditis observed in competitive athletes with COVID-19, the authors note that these recommendations can be reasonably applied to high-school athletes (aged 14 and older) along with adult recreational exercise enthusiasts.

Future study is needed, however, to better understand how long cardiac abnormalities persist following COVID-19 infection and the role of exercise training in long COVID.

The authors conclude that the current guidance is intended to help clinicians understand not only when testing may be warranted, but also when it is not.

“Given that it reflects the current state of knowledge through early 2022, it is anticipated that recommendations will change over time as our understanding evolves,” they say.

The 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19: Myocarditis, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and Return to Play will be discussed in a session at the American College of Cardiology’s annual scientific session meeting in Washington in April.

A version of this article first appeared on Medscape.com.

Cancer significantly raises a patient’s risk for cardiovascular morbidity and mortality, particularly within the first year after diagnosis and irrespective of cancer type, according to a population-based study.

The retrospective analysis, which included data from more than 200,000 patients with cancer, found that a new cancer diagnosis significantly increased the risk of cardiovascular (CV) death (hazard ratio [HR], 1.33) as well as other CV events, including stroke (HR, 1.44), heart failure (HR, 1.62) and pulmonary embolism (HR, 3.43).

From the results, the researchers concluded that a “new cancer diagnosis is independently associated with a significantly increased risk for cardiovascular death and nonfatal morbidity regardless of cancer site.”

The findings were published in the Journal of the American College of Cardiology: CardioOncology (2022 Mar;4[1]:85-94).

Patients with cancer and cancer survivors are known to have an increased risk for heart failure, but evidence on the risk for other CV outcomes remains less clear. In addition, the authors noted, many cancer therapies – including chest irradiation and chemotherapy – can increase a person’s risk of incident CV disease during treatment and after, but data on the long-term CV risk among cancer survivors conflict.

D. Ian Paterson, MD, of the University of Alberta, Edmonton, and coauthors wanted to clarify how a new cancer diagnosis at various sites and stages might affect a person’s risk for fatal and nonfatal CV events over the long term.

The current analysis included data from 224,016 patients with a new cancer diagnosis identified from an administrative database of more than 4.5 million adults residing in Alberta. The researcher identified 73,360 CV deaths and 470,481 nonfatal CV events between April 2007 and December 2018.

Comparing CV events in those with and in those without cancer, the authors found that patients with cancer had a 33% increased risk for CV mortality over the 12-year study follow-up, after adjusting for sociodemographic data and comorbidities (HR, 1.33; 95% confidence interval [CI], 1.29-1.37). Patients with cancer also had an increased risk for stroke (HR, 1.44), heart failure (HR, 1.62) and pulmonary embolism (HR, 3.43), though not myocardial infarction (HR, 1.01; 95% CI, 0.97 – 1.05), compared to those without cancer.

The extent of the risk varied somewhat by cancer stage, time from diagnosis, and cancer type.

A new cancer diagnosis put patients at a significantly higher risk of CV mortality, heart failure, stroke, or pulmonary embolism, regardless of the cancer site, but the risk of CV events was highest for patients with genitourinary, gastrointestinal, thoracic, nervous system, and hematologic malignancies. These patients accounted for more than half of the cancer cohort and more than 70% of the incident CV burden.

Patients with more advanced cancer were at the highest risk for poor CV outcomes, but even those with very early-stage disease faced an elevated risk.

The risk for CV events was greatest in the first year following a cancer diagnosis for all outcomes (HRs, 1.24-8.36) but remained significantly elevated for CV death, heart failure, and pulmonary embolism a decade later.

Overall, the authors concluded that “patients with cancer constitute a high-risk population for CV disease” over the long term and suggested that those with cancer “may benefit from comanagement that includes cardiologists as well as stroke and thrombosis specialists.”

In an accompanying editorial, Hiroshi Ohtsu of Juntendo University in Tokyo, and colleagues concluded that the work “has remarkable strengths” and important clinical implications. However, they said that additional steps may be warranted before translating these findings to clinical practice.

For example, the study is limited by its retrospective population-based design and the lack of data on cancer therapy as well as on several patient factors, including ethnicity, smoking, and physical activity.

The study authors agreed, noting that future work should evaluate how cancer therapies and other potential contributors to poor CV outcomes influence patients’ risk.

“Such work would potentially lead to better prediction of CV risk for patients with cancer and survivors and improved prevention and treatment strategies,” they wrote.

The study was supported by a foundation grant from the Canadian Institutes of Health Research. The authors have disclosed no relevant financial relationships. The editorial was supported in part by funding to individual authors from the Japan Society for the Promotion of Science/Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare, and the Agency for Medical Research and Development.

A version of this article first appeared on Medscape.com.

Cancer significantly raises a patient’s risk for cardiovascular morbidity and mortality, particularly within the first year after diagnosis and irrespective of cancer type, according to a population-based study.

The retrospective analysis, which included data from more than 200,000 patients with cancer, found that a new cancer diagnosis significantly increased the risk of cardiovascular (CV) death (hazard ratio [HR], 1.33) as well as other CV events, including stroke (HR, 1.44), heart failure (HR, 1.62) and pulmonary embolism (HR, 3.43).

From the results, the researchers concluded that a “new cancer diagnosis is independently associated with a significantly increased risk for cardiovascular death and nonfatal morbidity regardless of cancer site.”

The findings were published in the Journal of the American College of Cardiology: CardioOncology (2022 Mar;4[1]:85-94).

Patients with cancer and cancer survivors are known to have an increased risk for heart failure, but evidence on the risk for other CV outcomes remains less clear. In addition, the authors noted, many cancer therapies – including chest irradiation and chemotherapy – can increase a person’s risk of incident CV disease during treatment and after, but data on the long-term CV risk among cancer survivors conflict.

D. Ian Paterson, MD, of the University of Alberta, Edmonton, and coauthors wanted to clarify how a new cancer diagnosis at various sites and stages might affect a person’s risk for fatal and nonfatal CV events over the long term.

The current analysis included data from 224,016 patients with a new cancer diagnosis identified from an administrative database of more than 4.5 million adults residing in Alberta. The researcher identified 73,360 CV deaths and 470,481 nonfatal CV events between April 2007 and December 2018.

Comparing CV events in those with and in those without cancer, the authors found that patients with cancer had a 33% increased risk for CV mortality over the 12-year study follow-up, after adjusting for sociodemographic data and comorbidities (HR, 1.33; 95% confidence interval [CI], 1.29-1.37). Patients with cancer also had an increased risk for stroke (HR, 1.44), heart failure (HR, 1.62) and pulmonary embolism (HR, 3.43), though not myocardial infarction (HR, 1.01; 95% CI, 0.97 – 1.05), compared to those without cancer.

The extent of the risk varied somewhat by cancer stage, time from diagnosis, and cancer type.

A new cancer diagnosis put patients at a significantly higher risk of CV mortality, heart failure, stroke, or pulmonary embolism, regardless of the cancer site, but the risk of CV events was highest for patients with genitourinary, gastrointestinal, thoracic, nervous system, and hematologic malignancies. These patients accounted for more than half of the cancer cohort and more than 70% of the incident CV burden.

Patients with more advanced cancer were at the highest risk for poor CV outcomes, but even those with very early-stage disease faced an elevated risk.

The risk for CV events was greatest in the first year following a cancer diagnosis for all outcomes (HRs, 1.24-8.36) but remained significantly elevated for CV death, heart failure, and pulmonary embolism a decade later.

Overall, the authors concluded that “patients with cancer constitute a high-risk population for CV disease” over the long term and suggested that those with cancer “may benefit from comanagement that includes cardiologists as well as stroke and thrombosis specialists.”

In an accompanying editorial, Hiroshi Ohtsu of Juntendo University in Tokyo, and colleagues concluded that the work “has remarkable strengths” and important clinical implications. However, they said that additional steps may be warranted before translating these findings to clinical practice.

For example, the study is limited by its retrospective population-based design and the lack of data on cancer therapy as well as on several patient factors, including ethnicity, smoking, and physical activity.

The study authors agreed, noting that future work should evaluate how cancer therapies and other potential contributors to poor CV outcomes influence patients’ risk.

“Such work would potentially lead to better prediction of CV risk for patients with cancer and survivors and improved prevention and treatment strategies,” they wrote.

The study was supported by a foundation grant from the Canadian Institutes of Health Research. The authors have disclosed no relevant financial relationships. The editorial was supported in part by funding to individual authors from the Japan Society for the Promotion of Science/Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare, and the Agency for Medical Research and Development.

A version of this article first appeared on Medscape.com.

Cancer significantly raises a patient’s risk for cardiovascular morbidity and mortality, particularly within the first year after diagnosis and irrespective of cancer type, according to a population-based study.

The retrospective analysis, which included data from more than 200,000 patients with cancer, found that a new cancer diagnosis significantly increased the risk of cardiovascular (CV) death (hazard ratio [HR], 1.33) as well as other CV events, including stroke (HR, 1.44), heart failure (HR, 1.62) and pulmonary embolism (HR, 3.43).

From the results, the researchers concluded that a “new cancer diagnosis is independently associated with a significantly increased risk for cardiovascular death and nonfatal morbidity regardless of cancer site.”

The findings were published in the Journal of the American College of Cardiology: CardioOncology (2022 Mar;4[1]:85-94).

Patients with cancer and cancer survivors are known to have an increased risk for heart failure, but evidence on the risk for other CV outcomes remains less clear. In addition, the authors noted, many cancer therapies – including chest irradiation and chemotherapy – can increase a person’s risk of incident CV disease during treatment and after, but data on the long-term CV risk among cancer survivors conflict.

D. Ian Paterson, MD, of the University of Alberta, Edmonton, and coauthors wanted to clarify how a new cancer diagnosis at various sites and stages might affect a person’s risk for fatal and nonfatal CV events over the long term.

The current analysis included data from 224,016 patients with a new cancer diagnosis identified from an administrative database of more than 4.5 million adults residing in Alberta. The researcher identified 73,360 CV deaths and 470,481 nonfatal CV events between April 2007 and December 2018.

Comparing CV events in those with and in those without cancer, the authors found that patients with cancer had a 33% increased risk for CV mortality over the 12-year study follow-up, after adjusting for sociodemographic data and comorbidities (HR, 1.33; 95% confidence interval [CI], 1.29-1.37). Patients with cancer also had an increased risk for stroke (HR, 1.44), heart failure (HR, 1.62) and pulmonary embolism (HR, 3.43), though not myocardial infarction (HR, 1.01; 95% CI, 0.97 – 1.05), compared to those without cancer.

The extent of the risk varied somewhat by cancer stage, time from diagnosis, and cancer type.

A new cancer diagnosis put patients at a significantly higher risk of CV mortality, heart failure, stroke, or pulmonary embolism, regardless of the cancer site, but the risk of CV events was highest for patients with genitourinary, gastrointestinal, thoracic, nervous system, and hematologic malignancies. These patients accounted for more than half of the cancer cohort and more than 70% of the incident CV burden.

Patients with more advanced cancer were at the highest risk for poor CV outcomes, but even those with very early-stage disease faced an elevated risk.

The risk for CV events was greatest in the first year following a cancer diagnosis for all outcomes (HRs, 1.24-8.36) but remained significantly elevated for CV death, heart failure, and pulmonary embolism a decade later.

Overall, the authors concluded that “patients with cancer constitute a high-risk population for CV disease” over the long term and suggested that those with cancer “may benefit from comanagement that includes cardiologists as well as stroke and thrombosis specialists.”

In an accompanying editorial, Hiroshi Ohtsu of Juntendo University in Tokyo, and colleagues concluded that the work “has remarkable strengths” and important clinical implications. However, they said that additional steps may be warranted before translating these findings to clinical practice.

For example, the study is limited by its retrospective population-based design and the lack of data on cancer therapy as well as on several patient factors, including ethnicity, smoking, and physical activity.

The study authors agreed, noting that future work should evaluate how cancer therapies and other potential contributors to poor CV outcomes influence patients’ risk.

“Such work would potentially lead to better prediction of CV risk for patients with cancer and survivors and improved prevention and treatment strategies,” they wrote.

The study was supported by a foundation grant from the Canadian Institutes of Health Research. The authors have disclosed no relevant financial relationships. The editorial was supported in part by funding to individual authors from the Japan Society for the Promotion of Science/Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare, and the Agency for Medical Research and Development.

A version of this article first appeared on Medscape.com.

More than 18 months after the Watchman FLX device was licensed by the Food and Drug Administration for closure of the left atrial appendage (LAA), a prospective analysis of registry data presented at CRT 2022, sponsored by MedStar Heart & Vascular Institute, supports its safely outside of the clinical trial setting.

The data, drawn from the LAA occlusion registry of the National Cardiovascular Data Registry, showed a mortality rate at 45 days of under 1.0%, which was consistent with the acceptably low rate of other adverse events, according to Samir R. Kapadia, MD, chair of cardiovascular medicine at the Cleveland Clinic.

Only 0.5% had a pericardial effusion within 45 days of LAA closure that required intervention. Of those without effusion, 95% had a leak of less than 3 mm and 82% had no leak at all, according to Dr. Kapadia.

Patients enrolled in this analysis, called SURPASS (Surveillance Post Approval Analysis Plan), had undergone left atrial closure with the device from August 2020 to September 2022. There were no exclusion criteria. Ultimately, 2 years of follow-up is planned.

With more than 16,000 patients enrolled, the data on 14,363 patients in this initial 45-day analysis represents “the largest number of Watchman FLX patients evaluated to date,” Dr. Kapadia reported.
 

Device implantation success 97.5%

The Watchman FLX, which is delivered to the left atrial appendage by a transcatheter approach, was deployed successfully in 97.5% of all 16,048 patients enrolled in the registry. In the 398 cases without successful deployment, the anatomy was not conducive in nearly 70%. Other reasons included failure to meet device-release criteria and change in patient condition.

The outcomes of interest at 45 days were ischemic strokes, systemic emboli, device-related thrombi, device embolization, and bleeding. The primary endpoints at 2 years will be strokes and thrombotic events.

For stroke, the incidence within 45 days was 0.39%. About 25% of the strokes were hemorrhagic and the remainder were ischemic. There was 1 systemic embolism (0.01%), 5 device embolizations (0.03%), and 30 device-related thrombotic events (0.24%). Major bleeding occurred in 508 patients (3.55%).

For context, Dr. Kapadia compared these results to those observed in the PINNACLE FLX trial, which was a nonrandomized but prospective study of the Watchman FLX published about 1 year ago. In PINNACLE FLX, the enrollment was open to patients indicated for oral anticoagulation but who had an appropriate rationale for seeking a nonpharmacological alternative.

Taken from different studies, the outcomes at 45 days should not be construed as a direct comparison, but the similarity of the results can be considered reassuring, according to Dr. Kapadia.

For the composite safety endpoint of all-cause death, ischemic stroke, systemic embolism, or implantation-related events requiring intervention, the rates in SURPASS (0.4%) and PINNACLE FLX (0.5%) were nearly identical. Device leak rates (82.0% vs. 82.8%), stroke rates (0.4% vs. 0.7%), and all-cause death rates (0.9% vs. 0.5%) were also similar.

The similarity of the SURPASS and PINNACLE FLX data provides another level of reassurance.

“The SURPASS registry confirms the safety of the Watchman Flex in the real-world experience when the device is being used by many different operators in a large patient population,” Dr. Kapadia said in an interview.

In “appropriately selected patients,” the SURPASS data confirm that the Watchman FLX device “provides a safe and effective treatment option,” he added.

Relative to the PINNACLE FLX study, which enrolled 400 patients, it is noteworthy that the median age in SURPASS was older (76 vs. 73.8 years), a potential disadvantage in demonstrating comparable safety. The proportion of non-White patients was similar (6.7% vs. 6.3%). SURPASS had a higher proportion of women (40% vs. 35.5%).

Mitchel L. Zoler/MDedge News

The SURPASS data are credible, according to Vivek Y. Reddy, MD, director of cardiac arrhythmia services, Mount Sinai Health System, New York.

“While there are certainly limitations to registry data, I do feel pretty confident that these procedural complication and success rates [in SURPASS] do indeed reflect reality,” said Dr. Reddy, who was a coauthor of the PINNACLE FLX trial. In general, the SURPASS data “mirror most of our clinical experiences in routine clinical practice.”

With these registry data backing up multiple clinical studies, Dr. Reddy concluded, “I do believe that it is fair to say that Watchman-FLX implantation is a quite safe procedure.”

Dr. Kapadia reported no potential conflicts of interest. Dr. Reddy reported a financial relationship with Boston Scientific.

More than 18 months after the Watchman FLX device was licensed by the Food and Drug Administration for closure of the left atrial appendage (LAA), a prospective analysis of registry data presented at CRT 2022, sponsored by MedStar Heart & Vascular Institute, supports its safely outside of the clinical trial setting.

The data, drawn from the LAA occlusion registry of the National Cardiovascular Data Registry, showed a mortality rate at 45 days of under 1.0%, which was consistent with the acceptably low rate of other adverse events, according to Samir R. Kapadia, MD, chair of cardiovascular medicine at the Cleveland Clinic.

Only 0.5% had a pericardial effusion within 45 days of LAA closure that required intervention. Of those without effusion, 95% had a leak of less than 3 mm and 82% had no leak at all, according to Dr. Kapadia.

Patients enrolled in this analysis, called SURPASS (Surveillance Post Approval Analysis Plan), had undergone left atrial closure with the device from August 2020 to September 2022. There were no exclusion criteria. Ultimately, 2 years of follow-up is planned.

With more than 16,000 patients enrolled, the data on 14,363 patients in this initial 45-day analysis represents “the largest number of Watchman FLX patients evaluated to date,” Dr. Kapadia reported.
 

Device implantation success 97.5%

The Watchman FLX, which is delivered to the left atrial appendage by a transcatheter approach, was deployed successfully in 97.5% of all 16,048 patients enrolled in the registry. In the 398 cases without successful deployment, the anatomy was not conducive in nearly 70%. Other reasons included failure to meet device-release criteria and change in patient condition.

The outcomes of interest at 45 days were ischemic strokes, systemic emboli, device-related thrombi, device embolization, and bleeding. The primary endpoints at 2 years will be strokes and thrombotic events.

For stroke, the incidence within 45 days was 0.39%. About 25% of the strokes were hemorrhagic and the remainder were ischemic. There was 1 systemic embolism (0.01%), 5 device embolizations (0.03%), and 30 device-related thrombotic events (0.24%). Major bleeding occurred in 508 patients (3.55%).

For context, Dr. Kapadia compared these results to those observed in the PINNACLE FLX trial, which was a nonrandomized but prospective study of the Watchman FLX published about 1 year ago. In PINNACLE FLX, the enrollment was open to patients indicated for oral anticoagulation but who had an appropriate rationale for seeking a nonpharmacological alternative.

Taken from different studies, the outcomes at 45 days should not be construed as a direct comparison, but the similarity of the results can be considered reassuring, according to Dr. Kapadia.

For the composite safety endpoint of all-cause death, ischemic stroke, systemic embolism, or implantation-related events requiring intervention, the rates in SURPASS (0.4%) and PINNACLE FLX (0.5%) were nearly identical. Device leak rates (82.0% vs. 82.8%), stroke rates (0.4% vs. 0.7%), and all-cause death rates (0.9% vs. 0.5%) were also similar.

The similarity of the SURPASS and PINNACLE FLX data provides another level of reassurance.

“The SURPASS registry confirms the safety of the Watchman Flex in the real-world experience when the device is being used by many different operators in a large patient population,” Dr. Kapadia said in an interview.

In “appropriately selected patients,” the SURPASS data confirm that the Watchman FLX device “provides a safe and effective treatment option,” he added.

Relative to the PINNACLE FLX study, which enrolled 400 patients, it is noteworthy that the median age in SURPASS was older (76 vs. 73.8 years), a potential disadvantage in demonstrating comparable safety. The proportion of non-White patients was similar (6.7% vs. 6.3%). SURPASS had a higher proportion of women (40% vs. 35.5%).

Mitchel L. Zoler/MDedge News

The SURPASS data are credible, according to Vivek Y. Reddy, MD, director of cardiac arrhythmia services, Mount Sinai Health System, New York.

“While there are certainly limitations to registry data, I do feel pretty confident that these procedural complication and success rates [in SURPASS] do indeed reflect reality,” said Dr. Reddy, who was a coauthor of the PINNACLE FLX trial. In general, the SURPASS data “mirror most of our clinical experiences in routine clinical practice.”

With these registry data backing up multiple clinical studies, Dr. Reddy concluded, “I do believe that it is fair to say that Watchman-FLX implantation is a quite safe procedure.”

Dr. Kapadia reported no potential conflicts of interest. Dr. Reddy reported a financial relationship with Boston Scientific.

More than 18 months after the Watchman FLX device was licensed by the Food and Drug Administration for closure of the left atrial appendage (LAA), a prospective analysis of registry data presented at CRT 2022, sponsored by MedStar Heart & Vascular Institute, supports its safely outside of the clinical trial setting.

The data, drawn from the LAA occlusion registry of the National Cardiovascular Data Registry, showed a mortality rate at 45 days of under 1.0%, which was consistent with the acceptably low rate of other adverse events, according to Samir R. Kapadia, MD, chair of cardiovascular medicine at the Cleveland Clinic.

Only 0.5% had a pericardial effusion within 45 days of LAA closure that required intervention. Of those without effusion, 95% had a leak of less than 3 mm and 82% had no leak at all, according to Dr. Kapadia.

Patients enrolled in this analysis, called SURPASS (Surveillance Post Approval Analysis Plan), had undergone left atrial closure with the device from August 2020 to September 2022. There were no exclusion criteria. Ultimately, 2 years of follow-up is planned.

With more than 16,000 patients enrolled, the data on 14,363 patients in this initial 45-day analysis represents “the largest number of Watchman FLX patients evaluated to date,” Dr. Kapadia reported.
 

Device implantation success 97.5%

The Watchman FLX, which is delivered to the left atrial appendage by a transcatheter approach, was deployed successfully in 97.5% of all 16,048 patients enrolled in the registry. In the 398 cases without successful deployment, the anatomy was not conducive in nearly 70%. Other reasons included failure to meet device-release criteria and change in patient condition.

The outcomes of interest at 45 days were ischemic strokes, systemic emboli, device-related thrombi, device embolization, and bleeding. The primary endpoints at 2 years will be strokes and thrombotic events.

For stroke, the incidence within 45 days was 0.39%. About 25% of the strokes were hemorrhagic and the remainder were ischemic. There was 1 systemic embolism (0.01%), 5 device embolizations (0.03%), and 30 device-related thrombotic events (0.24%). Major bleeding occurred in 508 patients (3.55%).

For context, Dr. Kapadia compared these results to those observed in the PINNACLE FLX trial, which was a nonrandomized but prospective study of the Watchman FLX published about 1 year ago. In PINNACLE FLX, the enrollment was open to patients indicated for oral anticoagulation but who had an appropriate rationale for seeking a nonpharmacological alternative.

Taken from different studies, the outcomes at 45 days should not be construed as a direct comparison, but the similarity of the results can be considered reassuring, according to Dr. Kapadia.

For the composite safety endpoint of all-cause death, ischemic stroke, systemic embolism, or implantation-related events requiring intervention, the rates in SURPASS (0.4%) and PINNACLE FLX (0.5%) were nearly identical. Device leak rates (82.0% vs. 82.8%), stroke rates (0.4% vs. 0.7%), and all-cause death rates (0.9% vs. 0.5%) were also similar.

The similarity of the SURPASS and PINNACLE FLX data provides another level of reassurance.

“The SURPASS registry confirms the safety of the Watchman Flex in the real-world experience when the device is being used by many different operators in a large patient population,” Dr. Kapadia said in an interview.

In “appropriately selected patients,” the SURPASS data confirm that the Watchman FLX device “provides a safe and effective treatment option,” he added.

Relative to the PINNACLE FLX study, which enrolled 400 patients, it is noteworthy that the median age in SURPASS was older (76 vs. 73.8 years), a potential disadvantage in demonstrating comparable safety. The proportion of non-White patients was similar (6.7% vs. 6.3%). SURPASS had a higher proportion of women (40% vs. 35.5%).

Mitchel L. Zoler/MDedge News

The SURPASS data are credible, according to Vivek Y. Reddy, MD, director of cardiac arrhythmia services, Mount Sinai Health System, New York.

“While there are certainly limitations to registry data, I do feel pretty confident that these procedural complication and success rates [in SURPASS] do indeed reflect reality,” said Dr. Reddy, who was a coauthor of the PINNACLE FLX trial. In general, the SURPASS data “mirror most of our clinical experiences in routine clinical practice.”

With these registry data backing up multiple clinical studies, Dr. Reddy concluded, “I do believe that it is fair to say that Watchman-FLX implantation is a quite safe procedure.”

Dr. Kapadia reported no potential conflicts of interest. Dr. Reddy reported a financial relationship with Boston Scientific.