Effects of semaglutide on MACE irrespective of HF status

A pre-specified post-hoc analysis of the SELECT trial compared the efficacy and safety of semaglutide in patients with or without heart failure (HF). The results showed that semaglutide reduces major adverse cardiovascular events (MACE), HF-related events, and all-cause mortality consistently irrespective of HF status or HF subtype.

SELECT (NCT03574597) was a multicentre, double-blind, placebo-controlled, event-driven, superiority phase 3 trial evaluating the effect on MACE of semaglutide [1]. The 17,604 randomised participants with cardiovascular disease (CVD) and a BMI ≥27 kg/m², but no diabetes, were randomised to subcutaneous semaglutide 2 mg or 4 mg once a week or placebo. After a mean follow-up of 40 months, semaglutide reduced the relative risk of MACE by 20%. A pre-specified analysis of this study looked at time to first MACE (HF hospitalisation, urgent HF visit, or CV death), CV mortality, and total mortality in participants with HF (n=4,286) and without HF (n=13,314) [2].

The results were presented by Prof. John Deanfield (University College London, UK). The effect of semaglutide on the incidence of MACE did not differ between participants with HF (HR 0.72; 95% CI 0.60–0.87) and those without HF (HR 0.84; 95% CI 0.74–0.97; P_interaction=0.1934). The positive effect of semaglutide on the incidence of MACE was consistent in subgroups stratified by gender, age, and baseline characteristics such as BMI, NYHA class, and HbA1c level.

A consistent benefit was also observed after stratification by HF subtype: HR 0.65 (95% CI 0.49–0.87) for participants with HF with reduced ejection fraction (HfrEF; n=1,347) and 0.69 (95% CI 0.51–0.91) for those with preserved ejection fraction (HFpEF; n=2,273) (P_interaction=0.82). There was no significant interaction between HF status at baseline and treatment efficacy for the composite of HF hospitalisation, urgent visit for HF, or cardiovascular death: semaglutide was beneficial in patients with HF (HR 0.79; 95% CI 0.64–0.98), and in patients without HF (HR 0.85; 95% CI 0.68–1.06; P_interaction=0.64). The benefit for the composite of HF hospitalisation, urgent visits for HF, or cardiovascular death was consistent between HF subtypes. In addition, the effect for all-cause mortality was consistent between participants with HF (HR 0.81; 95% CI 0.66–1.00) and those without HF (HR 0.81; 95% CI 0.67–0.97; P_interaction=0.9797) nor between participants with HFrEF compared with HFpEF. The safety profile of semaglutide was similar in participants with or without HF and between HF subtypes.

“The efficacy data combined with a reassuring safety profile support the use of semaglutide to improve CV outcomes in a broad population of patients with atherosclerotic CVD and overweight or obesity, regardless of history of HF or HF subtype,” concluded Prof. Deanfield.

1. 
   
   1. Lincoff AM, et al. N Engl J Med 2023;389:2221–32.
   2. Deanfield J, et al. Semaglutide and cardiovascular outcomes in patients with overweight or obesity and heart failure: A pre-specified analysis from the SELECT trial. Late breaking clinical trials II, Heart Failure 2024, 11–14 May, Lisbon, Portugal.

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Posted on 16 July 2024