In a recent study published in The Lancet, researchers investigated whether semaglutide is beneficial in persons with atherosclerotic cardiovascular disease and a history of heart failure.
Study: Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial. Image Credit: MillaF/Shutterstock.com
Introduction
The global surge in obesity prevalence has led to a rapid increase in diabetes and cardiovascular disease. Semaglutide is a glucagon-like peptide-1 receptor agonist that causes weight loss and reduces major adverse cardiovascular events (MACEs) in diabetes patients.
Further, one trial observed that semaglutide reduced MACEs by 20% in non-diabetic patients with obesity/overweight and atherosclerotic cardiovascular disease.
The rise in 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 is likely causally related to the pathological outcomes of obesity.
While heart failure subtypes (preserved and reduced ejection fractions) share multiple clinical features, their cause and treatment response vary.
About the study
The present study examined the benefits of semaglutide in persons with heart failure and obesity. This was a prespecified analysis of the Semaglutide Effects on Heart Disease and Stroke in Patients with Obesity and Overweight (SELECT) trial.
Eligible subjects were adults aged ≥ 45 with a body mass index (BMI) ≥ 27 kg/m2 and an established cardiovascular disease (prior myocardial infarction, symptomatic peripheral artery disease, or hemorrhagic/ischemic stroke).
Subjects were randomized to receive a placebo or increasing doses of once-weekly semaglutide for 16 weeks.
The primary outcomes were time to the first occurrence of MACE, heart failure composite, cardiovascular mortality, and all-cause mortality. Heart failure composite was defined as an urgent hospital visit or hospitalization for heart failure or cardiovascular death.
MACE was defined as a composite of non-fatal stroke, non-fatal myocardial infarction, or cardiovascular death.
Time to an outcome was assessed using a Cox proportional hazards model. Safety was assessed as the nature and number of serious adverse events or those leading to discontinuation of the trial product.
Findings
Overall, 17,604 patients were randomized to semaglutide or placebo groups between October 31, 2018, and March 31, 2021. Their mean age and BMI were 61.6 years and 33.4 kg/m2, respectively.
Most participants (72.3%) were male, and 4,286 individuals had a history of heart failure at enrolment. Of these, 666 had an unclassified heart failure, 1,347 had heart failure with reduced ejection fraction, and 2,273 had heart failure with preserved ejection fraction.
Further, the clinical characteristics were well balanced between patients with and without (a history of) heart failure. There were more females among those with heart failure with preserved ejection fraction compared to those with heart failure with reduced ejection fraction.
Moreover, there were more patients with prior myocardial infarction in the heart failure with reduced ejection fraction group.
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 those with heart failure with preserved ejection fraction.
Besides, a higher proportion of patients with heart failure with reduced ejection fraction received aldosterone antagonists and loop diuretics.
None used an SGLT2 inhibitor at enrolment; however, 545 patients started using it during the study period. There were minor differences among patients by heart failure subtype.
For instance, those with an unclassified heart failure were older, more likely to be female, and had higher levels of high-sensitivity C-reactive protein. Besides, fewer patients with unclassified heart failure received β blockers at baseline than those in the other heart failure subtype groups.
Placebo subjects with heart failure at baseline had elevated rates of all outcomes relative to those without heart failure. Semaglutide improved all outcome measures in patients with heart failure.
Differences in event rates between semaglutide and placebo recipients emerged within six months, which increased over the follow-up. Notably, semaglutide similarly improved all-cause death and MACEs in patients without a history of heart failure.
Serious adverse events were less frequent in semaglutide recipients compared to placebo recipients, regardless of heart failure.
The most frequent serious adverse events were cardiac disorders. Among semaglutide recipients, treatment discontinuation due to adverse events was mainly driven by gastrointestinal disorders.
The discontinuation rate in semaglutide recipients was the lowest among those with heart failure with preserved ejection fraction.
Conclusions
Together, the findings indicate that semaglutide treatment decreased MACE and a heart failure composite endpoint in non-diabetic patients with atherosclerotic cardiovascular disease and obesity/overweight who had a history of heart failure at baseline.
The improved outcomes were evident soon after treatment initiation and sustained over the study period. Semaglutide benefits did not differ between patients with heart failure subtypes.
In addition, the clinical benefits of semaglutide were independent of sex, age, clinical status, and baseline BMI.
Overall, these efficacy results, along with an acceptable safety profile, support the use of semaglutide in addition to usual care to alleviate the risk of MACEs in a population with obesity/overweight and atherosclerotic cardiovascular disease, independent of the heart failure subtype.
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