Semaglutide eligibility in chronic coronary syndrome: are patients without prior myocardial infarction at comparable risk to the SELECT trial population?

Background European guidelines on chronic coronary syndrome (CCS) recommend considering semaglutide in patients with a body mass index (BMI) ≥27 kg/m² without diabetes to reduce the risk of major adverse cardiovascular events (MACE). This recommendation is largely based on the SELECT trial (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity), which exclusively enrolled patients with established atherosclerotic cardiovascular disease, defined as prior myocardial infarction (MI), stroke, or peripheral artery disease. Patients presenting with stable coronary artery disease without prior MI were not eligible, limiting the generalisability of these findings to the broader CCS population. Purpose To examine the five-year MACE risk among patients with CCS and BMI ≥27 kg/m² according to whether their index presentation was stable angina or MI. Methods This semi nationwide cohort study included 20,990 patients without diabetes from the Western Denmark Heart Registry who underwent first-time coronary angiography (CAG) between 2010 and 2021, with documented coronary artery disease and a procedural indication of stable angina (n=10,221) or MI (n=10,769). Follow-up began 60 days after the index CAG, at which point all patients were classified as having CCS. The primary outcome was MACE, defined as a composite of MI, ischaemic stroke, and cardiovascular death. Five-year cumulative incidence proportions were computed accounting for the competing risk of non-cardiovascular death. Cause-specific hazard ratios (HRs) were computed from Cox proportional hazards regression models adjusted for age, sex, hypertension, prior ischaemic stroke, peripheral artery disease, extent of coronary artery disease, and smoking status. Results Median follow-up was 5.0 years (Q1-Q3: 3.2-5.0), and median BMI was 29 kg/m² (Q1-Q3: 28-32) in both groups. Patients without prior MI were older than those with prior MI (median age 67 vs. 64 years). The five-year MACE risk was 7.7% (95% CI: 7.2–8.3) in patients with CCS without prior MI and 10.6% (95% CI: 10.0–11.3) in those with prior MI (Figure). After multivariable adjustment, the absence of prior MI was independently associated with a significantly lower rate of MACE (HR 0.73, 95% CI: 0.65–0.81). Conclusion Among patients with CCS and BMI ≥27 kg/m² without diabetes, those without prior MI had a substantially lower five-year MACE risk than those with prior MI. As the cardiovascular benefit of semaglutide has been established exclusively in the latter, higher-risk population, the current guideline recommendation to consider semaglutide across the broader CCS population may warrant re-evaluation. These findings highlight the need for dedicated evidence in those without prior MI before this recommendation can be uniformly extended.