In a study recently published in The Lancet, researchers investigated whether semaglutide could benefit patients with a history of atherosclerotic cardiovascular disease and heart failure.
study: Semaglutide and cardiovascular outcomes in patients with obesity and heart failure: a prespecified analysis from the SELECT trialImage credit: MillaF/Shutterstock.com
introduction
The global obesity epidemic is increasing, driving a rapid increase in diabetes and cardiovascular disease. Semaglutide is a glucagon-like peptide-1 receptor agonist that promotes weight loss and reduces major adverse cardiovascular events (MACE) in patients with diabetes.
Additionally, one study observed that semaglutide reduced MACE by 20% in non-diabetic patients with obesity/overweight and atherosclerotic cardiovascular disease.
Increasing obesity is also associated with an increased prevalence of heart failure. Most patients with obesity and heart failure have heart failure with preserved ejection fraction, which may be causally related to the pathological consequences of obesity.
Although the subtypes of heart failure (preserved and reduced ejection fraction) share several clinical features, their causes and treatment responses differ.
About the Research
The study investigated the benefits of semaglutide in patients with heart failure and obesity. This was a pre-specified analysis of the Semaglutide Effect on Heart Disease and Stroke in Obese and Overweight Patients (SELECT) trial.
The subjects were adults aged 45 years or older and with a BMI of 27 kg/m or more.2 and established cardiovascular disease (history of myocardial infarction, symptomatic peripheral arterial disease, or hemorrhagic/ischemic stroke).
Participants were randomized to receive either placebo or increasing doses of semaglutide once weekly for 16 weeks.
Primary outcomes were time to first MACE, composite heart failure, cardiovascular mortality, and all-cause mortality. Composite heart failure was defined as urgent hospital visit or hospitalization for heart failure or cardiovascular death.
MACE was defined as a composite of nonfatal stroke, nonfatal myocardial infarction, or cardiovascular death.
Time to outcome was assessed using Cox proportional hazards models.Safety was assessed as the nature and number of serious adverse events or adverse events leading to discontinuation of the study product.
Survey results
Overall, 17,604 patients were randomized to receive semaglutide or placebo between 31 October 2018 and 31 March 2021. Mean age and BMI were 61.6 years and 33.4 kg/m.2respectively.
The majority of participants (72.3%) were men, and 4,286 had a history of heart failure at enrollment: 666 with unclassifiable heart failure, 1,347 with reduced ejection fraction, and 2,273 with preserved ejection fraction.
Furthermore, clinical characteristics were well balanced between patients with and without heart failure: patients with heart failure with preserved ejection fraction were more likely to be female than those with reduced ejection fraction.
Furthermore, more patients in the heart failure with reduced ejection fraction group had suffered a previous myocardial infarction.
The incidence of heart failure with preserved ejection fraction was associated with higher baseline BMI. Patients with heart failure with reduced ejection fraction had lower mean systolic blood pressure than patients with heart failure with preserved ejection fraction.
Furthermore, patients with heart failure and reduced ejection fraction were more likely to receive aldosterone antagonists and loop diuretics.
No patients were using SGLT2 inhibitors at enrollment, but 545 patients initiated use during the study period. There were small differences between patients by heart failure subtype.
For example, patients with unclassifiable heart failure were older, more likely to be female, and had higher levels of high-sensitivity C-reactive protein. Furthermore, patients with unclassifiable heart failure were less likely to receive beta-blockers at baseline than patients in the other heart failure subtype groups.
Placebo subjects with heart failure at baseline had increased rates of all outcomes compared with subjects without heart failure.Semaglutide improved all outcome measures in patients with heart failure.
The difference in event rates between semaglutide and placebo groups emerged within 6 months and widened over the follow-up period. Of note, semaglutide similarly improved all-cause mortality and MACE in patients without a history of heart failure.
Regardless of the presence or absence of heart failure, patients receiving semaglutide experienced a lower incidence of serious adverse events than those receiving placebo.
The most frequent serious adverse events were cardiac events. Among patients receiving semaglutide, discontinuation due to adverse events was mainly due to gastrointestinal events.
The discontinuation rate in patients treated with semaglutide was lowest among patients with heart failure with preserved ejection fraction.
Conclusion
Taken together, these results indicate that semaglutide treatment reduced MACE and the composite heart failure endpoint in non-diabetic patients with atherosclerotic cardiovascular disease and obese/overweight with a history of heart failure at baseline.
Improvements were seen soon after starting treatment and sustained throughout the study. The benefit of semaglutide did not differ between patients with any of the heart failure subtypes.
Furthermore, the clinical benefit of semaglutide was independent of sex, age, clinical status, or baseline BMI.
Overall, these efficacy results, together with a tolerable safety profile, support the use of semaglutide in addition to usual care to reduce the risk of MACE in patient populations with obesity/overweight and atherosclerotic cardiovascular disease, regardless of heart failure subtype.