PLAINSBORO, N.J- Recently, The Lancet published a new pooled, participant-level analysis of patients with heart failure with mildly reduced ejection fraction or heart failure with preserved ejection fraction (HFpEF) from the SELECT, FLOW, STEP-HFpEF and STEP-HFpEF DM randomized, placebo-controlled trials.

According to the analysis, semaglutide led to a 31% reduced risk of combined cardiovascular (CV) death or worsening heart failure (HF) events, based on an incidence of 5.4% in patients assigned to semaglutide versus 7.5% in those assigned to placebo (HR 0.69; 95% CI 0.53-0.89; P=0.0045). Semaglutide also led to a 41% lower risk of worsening HF (2.8% versus 4.7% with placebo; HR 0.59 (95% CI 0.41-0.82), P=0.0019). There was no significant effect on the incidence of CV death (3.1% with semaglutide versus 3.7% with placebo); HR 0.82 (95% CI 0.57-1.16), P=0.25). The study did not adjust statistical analyses for multiplicity, so hazard ratios should not be used to infer definitive treatment effects. The US has not approved semaglutide for reducing heart failure outcomes.

The study was a pooled, post hoc participant-level analysis of 3,743 patients with a history of HFpEF from four randomized trials to examine the effects of once-weekly semaglutide (2.4 mg in SELECT, STEP-HFpEF, STEP-HFpEF DM; 1.0 mg in FLOW) on HF events.

The STEP-HFpEF Program enrolled participants with obesity-related HFpEF, while investigators reported the HFpEF classification for participants with atherosclerotic cardiovascular disease and overweight/obesity in SELECT and for those with type 2 diabetes and chronic kidney disease in FLOW. The main endpoint for this pooled analysis was a composite of time to first CV death or worsening HF event (hospitalizations or urgent visits due to HF). Additional endpoints included components of the composite: time to first HF event and time to CV death.

Experts consider obesity a key driver in the development of HFpEF, with approximately 80% of people with HFpEF living with overweight or obesity. Additionally, type 2 diabetes is highly prevalent among people with HFpEF and contributes to a greater symptom burden, worse functional capacity, and a more severely impaired quality of life.

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“Due in part to the obesity epidemic, HFpEF has emerged as the most common type of heart failure. Patients with obesity-related HFpEF are at high risk for serious complications including hospitalizations and death, and have limited treatment options, Collectively, this new analysis is the most comprehensive evaluation of semaglutide to date that assesses clinically relevant HF events, such as CV death and hospitalization.” said Dr. Mikhail Kosiborod, lead study author and cardiologist at Saint Luke’s Mid America Heart Institute.

“Combining the HFpEF participant populations across the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM trials allowed us to take a closer look at how semaglutide impacted patients living with this debilitating and often progressive condition, It is encouraging to have this additional analysis that examines the effect of semaglutide in this vulnerable patient population.” said Michelle Skinner, PharmD, Vice President Medical Affairs, Novo Nordisk.

Adverse events leading to treatment discontinuation occurred in 21% of patients in the semaglutide group and 13.9% of patients in the placebo group. Gastrointestinal disorders leading to treatment discontinuation occurred in 11.1% of patients in the semaglutide group and 2.7% of patients in the placebo group. Fewer semaglutide versus placebo-treated patients experienced serious adverse events across the four trial populations.