Lancet study shows semaglutide lowers risk of CV death or heart failure

A new analysis published in The Lancet has revealed significant findings related to heart failure with mildly reduced ejection fraction or heart failure with preserved ejection fraction (HFpEF). The pooled participant-level analysis involved 3,743 patients from the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomized, placebo-controlled trials.

The analysis showed that semaglutide, a medication, significantly reduced the risk of combined cardiovascular (CV) death or worsening heart failure (HF) events by 31%. This reduction was based on an incidence of 5.4% in patients treated with semaglutide compared to 7.5% in those given a placebo. Additionally, semaglutide led to a 41% lower risk of worsening HF events. However, there was no significant effect on the incidence of CV death itself. 

This study was a post hoc analysis pooling data from four trials to examine the effects of once-weekly semaglutide (2.4 mg in SELECT, STEP-HFpEF, STEP-HFpEF DM; 1.0 mg in FLOW). Participants in the STEP-HFpEF Program had obesity-related HFpEF, while in SELECT and FLOW, HFpEF classification was investigator-reported. The primary endpoint was a composite of time to first CV death or worsening HF event. Secondary endpoints included the time to first HF event and time to CV death.

Obesity is identified as a crucial factor in the development of HFpEF, with nearly 80% of HFpEF patients being overweight or obese. Additionally, type 2 diabetes is prevalent among HFpEF patients, further exacerbating symptoms and reducing quality of life.

Due to the obesity epidemic, HFpEF has become the most common type of heart failure. Dr. Mikhail Kosiborod, the lead study author and cardiologist at Saint Luke's Mid America Heart Institute, emphasized the high risk of serious complications in patients with obesity-related HFpEF, including hospitalizations and death. He noted the limited treatment options available for these patients, highlighting the significance of this new analysis in evaluating semaglutide's impact on clinically relevant HF events.

Adverse events led to treatment discontinuation in 21% of the semaglutide group and 13.9% of the placebo group. Gastrointestinal disorders were the primary reason for discontinuation, affecting 11.1% of the semaglutide group compared to 2.7% in the placebo group. However, fewer semaglutide-treated patients experienced serious adverse events across the trials.

Michelle Skinner, PharmD, Vice President of Medical Affairs at Novo Nordisk, expressed encouragement from the additional analysis, which examines semaglutide's effect on this vulnerable patient population.

Heart failure with preserved ejection fraction (HFpEF) occurs when the heart's ability to fill properly is impaired despite a normal ejection fraction. It accounts for approximately 50% of all heart failure cases. Despite advances in treating HFpEF, significant unmet needs remain. 

Obesity, a rapidly increasing condition, affects about 40% of US adults and is a key driver of HFpEF. Approximately 80% of HFpEF patients are overweight or obese, and 40-50% have diabetes.

The SELECT trial evaluated the efficacy of semaglutide 2.4 mg versus placebo in reducing major adverse cardiovascular events in people with established cardiovascular disease (CVD) and overweight or obesity. The STEP-HFpEF trials focused on semaglutide's effects on symptoms, physical function, and body weight in patients with HFpEF and obesity, with or without type 2 diabetes. The FLOW trial assessed semaglutide's impact on kidney outcomes in people with type 2 diabetes and chronic kidney disease (CKD).

These trials collectively provide comprehensive data on semaglutide's potential benefits in reducing heart failure outcomes, offering hope for improved treatment options for patients with HFpEF.

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