Adrian Hernandez, MD, from Duke University in Durham, North Carolina, and colleagues examined the impact of empagliflozin on first and recurrent heart failure events in patients after myocardial infarction in a double-blind, randomized trial. The study included 6522 patients hospitalized for acute myocardial infarction at risk for heart failure based on newly developed left ventricular ejection fraction of <45% and/or signs or symptoms of congestion.

The researchers found that the risk for first heart failure hospitalization and total heart failure hospitalizations was significantly lower in the empagliflozin group vs the placebo group during a median follow-up of 17.9 months (hazard ratio, 0.77 for first heart failure hospitalization; rate ratio, 0.67 for total heart failure hospitalizations).

For first and total heart failure hospitalizations, the benefit of empagliflozin was consistent across clinically relevant patient subgroups. Patients randomly assigned to empagliflozin had less postdischarge need for new use of diuretics, renin-angiotensin modulators, and mineralocorticoid receptor antagonists.

“These data suggest the potential role for empagliflozin in high-risk post-myocardial infarction patients in preventing heart failure hospitalizations,” the authors write.

Several authors disclosed ties to biopharmaceutical companies, including Boehringer Ingelheim and Eli Lilly, which manufacture empagliflozin and funded the study.

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Javed Butler, MD, MPH, from the Baylor Scott and White Research Institute in Dallas, and colleagues randomly assigned patients hospitalized for acute myocardial infarction who were at risk for heart failure to empagliflozin 10mg daily or placebo in addition to standard care within 14 days after admission (3260 and 3262 patients, respectively).

The researchers found that a first hospitalization for heart failure or death from any cause occurred in 8.2 and 9.1% of patients in the empagliflozin and placebo groups, respectively, during a median follow-up of 17.9 months (incidence rates, 5.9 and 6.6 events, respectively, per 100 patient-years; hazard ratio, 0.90; 95% CI, 0.76 to 1.06; P =.21). A first hospitalization for heart failure occurred in 3.6 and 4.7% of patients in the empagliflozin and placebo groups, respectively (hazard ratio, 0.77; 95% CI, 0.60 to 0.98), and death from any cause occurred in 5.2 and 5.5%, respectively (hazard ratio, 0.96; 95% CI, 0.78 to 1.19). Adverse events were consistent with the known safety profile for empagliflozin.

“Empagliflozin did not reduce the risk of the composite primary end point event, a first hospitalization for heart failure or death from any cause, in patients with acute myocardial infarction who were at increased risk for heart failure,” the authors write.

Several authors disclosed ties to pharmaceutical companies, including Boehringer Ingelheim and Eli Lilly, which manufacture empagliflozin and funded the study.

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HealthDay News — A low dietary sodium diet, including intake below the standard recommended maximum of 2.3g per day, is associated with an increased risk for in-hospital mortality among patients with heart failure, according to a study presented at the annual meeting of the American College of Cardiology, held from March 4 to 6 in New Orleans.

Anirudh Palicherla, MD, from the Creighton University School of Medicine in Omaha, Nebraska, and colleagues conducted a meta-analysis of randomized clinical trials to compare low dietary sodium to usual care in heart failure. Data were included from 9 studies with 3499 patients.

The researchers found that the low dietary sodium group showed a significant increase in in-hospital mortality compared with usual care (risk ratio, 1.84 [95% CI, 1.46 to 2.31; P <.001] for intake <2.5g/day vs ≥2.5g/day). No significant difference was seen between the groups in hospitalization (risk ratio, 1.45; 95% CI, 0.99 to 2.11; P =.05).

“Our findings showed that restricting dietary sodium to less than the usual recommendation was counterproductive in the management of heart failure,” Palicherla said in a statement. “This study shows that the focus should be on establishing a safe level of sodium consumption instead of overly restricting sodium.”

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Mikhail N. Kosiborod, MD, from Saint Luke’s Mid America Heart Institute in Kansas City, Missouri, and colleagues randomly assigned 616 patients who had heart failure with preserved ejection fraction, a body mass index of 30 kg/m² or more, and type 2 diabetes to receive semaglutide or placebo once a week for 52 weeks. The change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and change in body weight were the primary endpoints.

The researchers found that the mean change in KCCQ-CSS was 13.7 and 6.4 points with semaglutide and placebo, respectively, and the corresponding mean percentage changes in body weight were −9.8% and −3.4%. For the confirmatory secondary endpoints, including the estimated between-group difference in change in 6-minute walk distance and estimated treatment ratio for change in C-reactive protein level, the results favored semaglutide over placebo. Serious adverse events were reported in 17.7% and 28.8% of those in the semaglutide and placebo groups, respectively.

“Once-weekly semaglutide at a dose of 2.4 mg led to larger reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo at 52 weeks,” the authors write.

Several authors disclosed ties to biopharmaceutical companies, including Novo Nordisk, which manufactures semaglutide and funded the study.

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Kim L. Feingold, PhD, from Northwestern University Feinberg School of Medicine in Chicago, and colleagues randomly assigned (1:1) patients undergoing primary valve surgery via sternotomy to acupuncture (51 individuals) or standard care (49 individuals). Daily inpatient acupuncture sessions started on postoperative day 1.

The researchers found that an average of 3.8 acupuncture sessions were delivered per patient during a mean hospital stay of 4.6 days. Acupuncture was associated with lower pain, nausea, stress, and anxiety after each session and across admission vs standard care. Additionally, acupuncture was associated with a lower incidence of postoperative atrial fibrillation (acupuncture, 13.7%; standard care, 32.7%), fewer discharges on amiodarone (acupuncture, 9.8%; standard care, 26.5%), and fewer hours in the intensive care unit (acupuncture, 30.3; standard care, 37.0).

“We learned that acupuncture after open heart surgery is feasible in this fast-paced environment, even in the intensive care unit the day after surgery, and was well tolerated by patients with no adverse effects,” Feingold said in a statement. “The majority of patients had no prior history with acupuncture, demonstrating their openness to receive integrative therapies after surgery. Overall, patients reported that it was a pleasant and positive aspect of their cardiovascular surgery recovery.”

Several authors disclosed ties to the medical technology industry.

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HealthDay News — Bempedoic acid is associated with a reduction in major adverse cardiovascular events among statin-intolerant primary prevention patients, according to a study published online June 24 in the Journal of the American Medical Association to coincide with the annual meeting of the American Diabetes Association, held from June 23 to 26 in San Diego.

Steven E. Nissen, MD, from the Cleveland Clinic, and colleagues conducted a masked, randomized trial involving 13,970 statin-intolerant patients, including 4206 primary prevention patients to determine the effects of bempedoic acid on cardiovascular outcomes. Participants were randomly assigned to oral bempedoic acid or matching placebo (2100 and 2106 patients, respectively).

The researchers found that bempedoic acid reduced low-density lipoprotein cholesterol levels by 30.2mg/dL and high-sensitivity C-reactive protein levels by 0.56mg/L compared with placebo (reductions of 21.3 and 21.5%, respectively). A significant risk reduction was seen in the primary end point of first occurrence of any component of a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization (111 vs 161 events [5.3 vs 7.6%; adjusted hazard ratio, 0.70]) during follow-up for a median of 39.9 months. Significant risk reductions were also seen in key secondary end points, including the composite of cardiovascular death, MI, or stroke; MI; cardiovascular death; and all-cause mortality (hazard ratios, 0.64, 0.61, 0.61, and 0.73, respectively).

“Administration of bempedoic acid in patients unable or unwilling to take guideline recommended doses of a statin was associated with a significant reduction in the primary end point, four-component major adverse cardiovascular events,” the authors write.

Several authors disclosed ties to pharmaceutical companies, including Esperion Therapeutics, which manufactures bempedoic acid and funded the study.

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HealthDay News — For individuals with diabetes without preexisting cardiovascular disease, the addition of glucagon-like peptide 1 receptor agonists (GLP1-RA) is associated with a lower risk for major adverse cardiac events (MACE) and heart failure, according to a study published online May 9 in the Annals of Internal Medicine.

Tadarro L. Richardson Jr., MD, from the VA Tennessee Valley Healthcare System Geriatric Research Education Clinical Center in Nashville, and colleagues examined whether MACE incidence is lower with the addition of GLP1-RA or sodium-glucose cotransporter 2 inhibitors (SGLT2i) vs dipeptidyl peptidase-4 inhibitors (DPP4i) onto metformin, sulfonylurea, or insulin treatment alone or in combination. A total of 28,759 GLP1-RA versus 28,628 DPP4i weighted pairs and 21,200 SGLT2i vs 21,170 DPP4i weighted pairs were included in the study.

The researchers found lower MACE and heart failure risk in association with GLP1-RA vs DPP4i (adjusted hazard ratio, 0.82; 95% CI, 0.72 to 0.94), for an adjusted risk difference of 3.2 events per 1000 person-years. There was no association observed for SGLT2i versus DPP4i with MACE and heart failure (adjusted hazard ratio, 0.91; 95% CI, 0.78 to 1.08).

“These findings are hypothesis generating, and further evaluation of these medications as part of primary [cardiovascular disease] prevention strategy is needed,” the authors write.

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HealthDay News — For women, adherence to a Mediterranean diet is associated with a reduced risk for cardiovascular disease (CVD) and mortality, according to a review published online March 14 in Heart.

Anushriya Pant, from the University of Sydney, and colleagues examined the association between higher vs lower adherence to a Mediterranean diet and incident CVD and total mortality among women in a systematic review and meta-analysis. The meta-analysis included 16 prospective cohort studies with 722,495 female participants.

The researchers found that higher adherence to a Mediterranean diet was associated with lower CVD incidence, total mortality, and coronary heart disease (hazard ratios [95% CI], 0.76 [0.72 to 0.81], 0.77 [0.74 to 0.80], and 0.75 [0.65 to 0.87], respectively). Women with higher Mediterranean diet adherence had lower stroke incidence, but the reduction was not statistically significant (hazard ratio, 0.87; 95% CI, 0.76 to 1.01).

“Future research might consider adding more studies that look at the dietary impact on stroke, and subgroup analyses that address female specific cardiovascular risk factors, menopausal status and ethnicity, as well as individual participant data meta-analyses,” the authors write.

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Aficamten is an investigational oral, selective, small molecule cardiac myosin inhibitor designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle, thereby suppressing the myocardial hypercontractility associated with hypertrophic cardiomyopathy.

The multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT05186818) included 282 adults with symptomatic HCM and left ventricular outflow tract obstruction. Study participants were randomly assigned to receive oral tablets of aficamten 5mg, 10mg, 15mg, and 20mg or placebo for up to 24 weeks. The primary endpoint was the change in peak oxygen uptake (pVO₂) by cardiopulmonary exercise testing.

Findings demonstrated that treatment with aficamten was associated with a significant increase in pVO₂ at week 24 compared with placebo (least-square mean difference of 1.74mL/kg/min [95% CI, 1.04-2.44]; P =.000002); this treatment effect was consistent across all prespecified subgroups including patients receiving or not receiving background beta-blocker therapy. 

Additionally, the trial met all 10 prespecified secondary endpoints (all P <.0001). This included the change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score at weeks 12 and 24, the proportion of patients with at least a 1 class improvement in New York Heart Association functional class at weeks 12 and 24, change in provoked left ventricular outflow tract gradient and the proportion of patients with post-Valsalva gradient less than 30mmHg at weeks 12 and 24, along with exercise workload and guideline-eligibility for septal reduction therapy.

As for safety, aficamten was well tolerated with an adverse event profile comparable to placebo. There were no reports of worsening heart failure or treatment interruptions due to low left ventricular ejection fraction. 

Full trial data will be presented at an upcoming medical conference. The Food and Drug Administration previously granted Breakthrough Therapy designation to aficamten for this indication.

“Cardiac myosin inhibition represents an exciting new therapy option for patients with symptomatic obstructive HCM and I am pleased to see these impressive results from SEQUOIA-HCM,” said Martin Maron, MD, Director, Hypertrophic Cardiomyopathy Center, Lahey Hospital and Medical Center, Burlington, MA; Tufts University School of Medicine, and National Principal Investigator of SEQUOIA-HCM. “A therapy like aficamten that improves exercise capacity in a clinically meaningful manner, absent low LVEF events that interrupt treatment, should be a welcome addition for HCM patients as well as the clinicians who treat them.”

HealthDay News — The Predicting Risk of Cardiovascular Disease (CVD) Events (PREVENT) risk calculator estimates the risk for CVD, including heart failure, according to a methods paper and accompanying scientific statement published online November 10 in Circulation to coincide with the American Heart Association Scientific Sessions 2023, held from November 11 to 13 in Philadelphia.

Sadiya S. Khan, MD, from the Northwestern University Feinberg School of Medicine in Chicago, and colleagues developed and validated the PREVENT equations among US adults aged 30 to 79 years without known CVD. The derivation sample included individual-level participant data from 25 datasets with 3,281,919 participants; external validation was performed in 3,330,085 participants from 21 additional datasets. Predictors included traditional risk factors and estimated glomerular filtration rate (eGFR). The researchers identified 211,515 incident total CVD events during a mean follow-up of 4.8 years. In external validation for CVD, the median C-statistics were 0.794 and 0.757 in female and male participants, respectively. For men and women, the calibration curves were 1.03 and 0.94, respectively. Similar estimates for discrimination and calibration were seen for atherosclerotic CVD- and heart failure-specific models.

In a scientific statement, Khan and colleagues discuss the clinical implications of the PREVENT equations. The authors note that use of the equations allows 10- and 30-year risk estimates for total CVD (composite of atherosclerotic CVD and heart failure). The sex-specific risk equations include eGFR as a predictor and remove race from risk prediction estimates.

“The PREVENT equations are a critical first step toward including cardiovascular-kidney-metabolic health and social factors in risk prediction for CVD,” Khan said in a statement.

Several authors disclosed ties to the biopharmaceutical industry.

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A. Michael Lincoff, MD, from the Cleveland Clinic, and colleagues assessed whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes. The analysis included 17,604 patients (aged 45 years and older) with preexisting cardiovascular disease and a body mass index 27kg/m² or greater who were randomly assigned to once-weekly subcutaneous semaglutide at a dose of 2.4mg or placebo.

The researchers found that during a mean duration of exposure to semaglutide or placebo of 34.2 months and a mean follow-up of 39.8 months, a primary cardiovascular end-point event (death or nonfatal heart attack or stroke) occurred in 6.5% of the semaglutide group and in 8.0 percent of the placebo group (hazard ratio, 0.80). Discontinuation due to adverse events occurred in 16.6 percent of participants in the semaglutide group and among 8.2% in the placebo group.

“The magnitude of the effect of semaglutide in the current trial was similar to that among patients with diabetes in previous studies (within the constraints of between-trial comparisons), which suggests that treatment with semaglutide could be applied more broadly for secondary prevention of cardiovascular events in the expanding population of patients with overweight and obesity and atherosclerotic vascular disease,” the authors write.

The study was funded by Novo Nordisk, the manufacturer of semaglutide.

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Acute kidney injury (AKI) and chronic kidney disease (CKD) progression are less likely with direct oral anticoagulants (DOACs) vs vitamin K antagonists for atrial fibrillation, investigators reported at the American Society of Nephrology’s Kidney Week 2022 conference in Orlando, Florida.

Ane Emilie Friis Vestergaard, MD, of Aarhus Universitet Klinisk Epidemiologisk Afdeling in Aarhus, Denmark, and colleagues conducted an active comparative study that included 33,670 patients with atrial fibrillation initiating anticoagulant therapy. Of these, 77% started therapy with DOACs. Patients had a mean age of 75 years, 48% were women, and 25% had an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m². The median follow-up was 2.3 years.

During the first year of treatment, the cumulative risk for AKI was 13.9% in the DOAC group and 15.5% in the vitamin K antagonist group. The 5-year risk for CKD progression was 14.0% in the DOAC group and 15.4% among vitamin K antagonist users.

Compared with vitamin K antagonist users, those in the DOAC group had significant 15% and 16% lower risks for AKI and CKD progression, respectively, Dr Vestergaard’s team reported. Results were similar across subgroups of sex, age, diabetes, and baseline eGFR.

The investigators defined AKI according to KDIGO criteria and CKD progression as a composite of a greater than 30% decrease in eGFR or kidney failure.

Reference

Vestergaard AEF, Jensen SK, Heide-Jørgensen U, et al. Oral anticoagulant therapy and risk of kidney disease: A nationwide cohort study. Presented at: Kidney Week 2022; November 3-6, Orlando, Florida. Abstract TH-OR04.

The Food and Drug Administration (FDA) has granted Fast Track designation to asundexian for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

Asundexian is an investigational oral Factor XIa (FXIa) inhibitor. According to Bayer, asundexian acts selectively on the coagulation cascade, thereby offering the potential to prevent events without the increased bleeding risk.

The Company is currently enrolling patients in the phase 3 OCEANIC-AF study (ClinicalTrials.gov Identifier: NCT05643573). In OCEANIC-AF, the safety and efficacy of asundexian will be compared with apixaban in patients with atrial fibrillation at risk for stroke.

“This designation provides an opportunity to accelerate the development of asundexian and quickly address current patient needs,” said Christian Rommel, Member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Head of Research and Development. “Asundexian is currently investigated as a candidate in an entirely new class of antithrombotic treatment options aiming to selectively modulate coagulation, address patients with concerns of bleeding, and focus on indications where current anticoagulation is not used.”

The FDA’s Fast Track designation helps to accelerate the development and review of products for serious and life-threatening conditions where no treatment exists or where the investigational therapy is likely to provide an advantage over currently available treatments.

Asundexian was previously fast tracked for secondary prevention in patients after a noncardioembolic ischemic stroke. The phase 3 OCEANIC-STROKE study (ClinicalTrials.gov Identifier: NCT05686070) will investigate the efficacy and safety of asundexian for prevention of ischemic stroke compared with placebo on top of standard of care antiplatelet therapy in patients after a noncardioembolic ischemic stroke or high-risk transient ischemic attack.

(HealthDay News) — For 6 cardiovascular diseases (CVDs) examined, coverage of evidence-based medications varies by low-cost generic program (LCGP), drug, and condition, according to a study published online Sept. 5 in the Annals of Internal Medicine.

Ivy T. Ton, PharmD, from the Western University of Health Sciences in Pomona, California, and colleagues examined LCGPs’ coverage of evidence-based CVD medications in a cross-sectional study of 19 publicly available LCGPs in March and April 2023 in the United States. The proportion of LCGPs that offered evidence-based CVD medicines for 6 CVDs was examined according to 4 metrics (breadth, choice, high-quality evidence, and titratability).

The researchers found variation in the availability of CVD medication by program, drug, and CVD condition. Some of the programs had greater breadth and choice of coverage for most CVDs, while many had more focused coverage, and limited offerings were provided by others.

Angiotensin-converting enzyme inhibitors, β-blockers, thiazides, and moderate-intensity statins were offered by nearly all LCGPs, while lower availability was seen for higher-cost or lower-use generics, including antiplatelets and antiarrhythmics. For atrial fibrillation and heart failure, core pharmacotherapy coverage and choices were limited, while for hypertension and hyperlipidemia, they were widely available.

“Medication coverage in LCGPs varies widely for core, evidence-based CVD medications in all CVD conditions investigated, with differences in medication coverage options and strengths by program and condition,” the authors write. “Health care professionals should consider medication availability and LCGP-specific characteristics when recommending their use.”

One author disclosed ties to the pharmaceutical industry and one to the medical device industry.

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