Semaglutide Shows Potential for Significant CVD Prevention in Analysis of Real-World Data

Analysis of Danish heart registry data suggest that treatment with semaglutide (Wegovy; Novo Nordisk) of adults with obesity, with a first myocardial infarction (MI), and without diabetes could reduce 1 major adverse cardiovascular event (MACE) for every 49 individuals treated and that the 5-year risk of MACE in this population would be 10.7%.

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The estimates are based on analysis of more than 34 000 participants in the Western Denmark Heart Registry of which 31% met eligibility criteria for the SELECT (Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes) clinical trial and so for treatment with the incretin mimetic.

Findings from the analysis of real-world data could prove valuable for clinicians and regulators regarding patient selection for and the preventive potential of the injectable glucagon-like peptide-1 (GLP-1) receptor agonist, Michael Maeng, MD, PhD, clinical professor in the department of cardiological medicine at Aarhus University Hospital, Denmark, and colleagues wrote in a research letter in the Journal of the American College of Cardiology.

The SELECT trial results were presented at the 2023 American Heart Association Scientific Sessions in November and showed that treatment with semaglutide reduced the risk of MACE (ie, CV death, nonfatal MI or nonfatal stroke) by 20% compared with placebo (HR 0.8; 95% CI, 0.72-0.9) in participants with overweight or obesity, existing CVD, and without diabetes. Maeng and colleagues set out to estimate, based on a real-world population in a “low-risk European country,” the prevalence of individuals meeting the eligibility criteria for the SELECT trial, the 5-year MACE incidence, and the corresponding number needed to treat (NNT) to reduce one MACE.

The research team culled data from the Western Denmark Heart Registry for 34 405 participants aged 45 years and older with a first-time MI and coronary artery disease from 2010 to 2021 and then applied SELECT trial inclusion criteria to the cohort: age as indicated, without diabetes and with a body mass index (BMI) of 27 kg/m2 or higher. Of the original cohort, 31% were “SELECT-eligible to treatment with semaglutide,” the authors wrote.

Among the group of 10 769 SELECT-eligible participants, mean BMI was 29 kg/m2; median age was 64 years; 32% were smokers and 53% had hypertension. The researchers estimated 5-year cumulative incidence proportions controlling for the competing risk for non-CV death. The estimate of the potential of semaglutide to prevent a single MACE over 5 years (NNT) was based on observed cumulative incidence and assumed treatment efficacy similar to that observed in the SELECT trial.

During the median 5-year follow-up, researchers observed 972 MACE events among the SELECT-eligible patients and 544 recurrent MIs, 174 ischemic strokes and 338 CV deaths. The 5-year MACE incidence was 10.7% (95% CI, 10-11.3) among the SELECT-eligible patients. The estimated NNT to prevent one MACE event was 49 patients (95% CI, 35-98).

“These results are of paramount importance to regulatory authorities and clinicians when implementing semaglutide in clinical practice,” Maeng and colleagues concluded.

Source: Hansen MK, Olesen KKW, Gyldenkerne C, et al. Eligibility for and preventive potential of semaglutide in overweight and obese patients with myocardial infarction. [research letter] J Am Coll Cardiol. 2024;83(9):956-958. https://www.jacc.org/doi/10.1016/j.jacc.2023.12.029