Semaglutide cuts risk for worsening heart failure, CV death among adults with HFpEF
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Key takeaways:
- Semaglutide lowered the risk for worsening heart failure or CV death by 31% compared with placebo.
- The risk for a worsening heart failure event was 41% lower in the semaglutide group vs. placebo.
Semaglutide cut the risk for worsening heart failure and CV death for adults with HF with preserved ejection fraction, according to data presented at the European Society of Cardiology Congress and simultaneously published in The Lancet.
As Healio previously reported from the STEP-HFpEF trial, semaglutide (Ozempic/Wegovy, Novo Nordisk) was associated with improvements in HF symptom burden among adults with HFpEF and obesity. In a pooled analysis of data from STEP-HFpEF, STEP-HFpEF DM, FLOW and SELECT, all funded by Novo Nordisk, researchers observed semaglutide 1 mg or 2.4 mg reduced risk for worsening HF events and CV death compared with placebo.
“In this pooled analysis of patients with heart failure and preserved ejection fraction across the SELECT, FLOW, STEP-HFpEF and STEP-HFpEF diabetes trials, semaglutide significantly reduced the risk of cardiovascular death or worsening heart failure as compared with placebo, as well as worsening heart failure events alone, but the effects on cardiovascular death were not significant,” Mikhail Kosiborod, MD, FACC, FAHA, cardiologist at Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri-Kansas City School of Medicine, said during a presentation.
Kosiborod and colleagues conducted a post hoc pooled analysis of the four trials in which participants were randomly assigned to 1 mg or 2.4 mg semaglutide or placebo. The analysis included 3,743 adults with a history of HFpEF at baseline (median age, 64 years; 38.1% women; 90.4% white). The primary endpoint was a composite of time to worsening HF event or CV death. Worsening HF was defined as hospitalization or an urgent visit for HF.
Semaglutide cuts risk for worsening HF
Adults receiving semaglutide had a lower risk for CV death or worsening HF than those receiving placebo (5.4% vs. 7.5%; HR = 0.69; 95% CI, 0.53-0.89; P = .0045). The number needed to treat to prevent a primary endpoint event was 97 over 1 year and 28 over 4 years.
When the endpoint events were assessed individually, semaglutide was associated with a reduction in risk for worsening HF compared with placebo (2.8% vs. 4.7%; HR = 0.59; 95% CI, 0.41-0.82; P = .0019). The number needed to treat to prevent a worsening HF event was 95 over 1 year and 30 over 4 years.
There was no difference in risk for CV death between the semaglutide and placebo groups (semaglutide, 3.1%; placebo, 3.7%; P = .25). The researchers attributed the lack of risk reduction to there being only 126 events of CV death and the analysis not being adequately powered for the outcome.
“These effects of semaglutide were highly consistent across various subgroups of patients, including by ejection fraction — in those with mildly reduced as well as preserved ejection fraction — as well as in people who did or did not receive SGLT2 inhibitors or [mineralocorticoid receptor antagonists],” Kosiborod said during the presentation. “The effects were more pronounced in patients with higher BMI, and attenuated in those with lower BMI.”
The associations observed in the main analysis were similar in sensitivity analyses restricting urgent HF visits in the FLOW trial to adults requiring IV therapy and when investigator-reported events of hospitalization and urgent visits due to HF were used instead of adjudicated events.
The safety profile among the study population was similar to what was observed in the four trials. Serious adverse events were reported by a lower percentage of the semaglutide group compared with placebo (29.9% vs. 38.7%). The study medication was discontinued by 9.6% of the placebo group and 7.4% of those receiving semaglutide. The semaglutide group had a higher proportion of participants experiencing gastrointestinal events leading to drug discontinuation than placebo (11.1% vs. 2.7%).
“Collectively, these data certainly support semaglutide as an efficacious treatment option in people with heart failure and preserved ejection fraction, not just in terms of improvements in symptoms and physical limitations, as we showed previously in the STEP-HFpEF program, but also now for reducing clinical events such as cardiovascular death and worsening heart failure,” Kosiborod said during the presentation.
Semaglutide benefits beyond weight loss
In a related editorial published in The Lancet, Camilla Hage, PhD, associate professor in the division of cardiology, department of medicine at Karolinska Institutet in Stockholm, said more research is needed to determine whether semaglutide and GLP-1 receptor agonists lower the risk for worsening HF among adults without overweight or obesity, as the risk reduction in the pooled analysis may be due to weight loss. She also said more studies are needed to explore the efficacy of GLP-1s on worsening HF among adults with HF with reduced ejection fraction. However, Hage concluded the data from the pooled analysis support a “more compelling use” for semaglutide beyond treating obesity.
“Patients and clinicians must consider trial results, but also aggregate data interpretation in guidelines regulatory labeling, payer reimbursement and, as exemplified by GLP-1 receptor agonists, drug availability,” Hage wrote. “Ultimately, implementation will also be determined by published data on, and stakeholder perceptions of, cost-effectiveness, unmet needs, clinically meaningful risk reductions and side effects, and general familiarity across medical disciplines.”
References:
- Hage C, et al. Lancet. 2024;doi:10.1016/S0140-6736(24)01763-X.
- Kosiborod MN, et al. Lancet. 2024;doi:10.1016/S0140-6736(24)01643-X.
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Kosiborod MN, et al. Clinical trial updates on the GLP-1 receptor agonist, semaglutide. Presented at: European Society of Cardiology Congress; Aug. 30-Sept. 2, 2024; London (hybrid meeting).
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