Identifying High-Risk Obese Individuals Without Diabetes for GLP-1RA Therapy Using Coronary CTA.

BACKGROUND: The SELECT trial demonstrated that semaglutide reduced major adverse cardiovascular events among individuals with cardiovascular disease (CVD) and overweight/obesity without diabetes. We hypothesized that coronary artery disease (CAD) detected by coronary computed tomography angiography (CCTA) identifies individuals with similar cardiovascular risk. OBJECTIVES: The aim of the study was to evaluate the association between CAD severity by CCTA and cardiovascular outcomes among individuals resembling The SELECT (Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes) trial population but without known CVD. METHODS: We included individuals aged ≥45 years with body mass index ≥27 kg/mundergoing CCTA at 2 centers. EXCLUSIONS: prior myocardial infarction, revascularization, stroke, diabetes, end-stage kidney disease, or malignancy. CAD severity was categorized as absent (0%), nonobstructive (1%-49%), or obstructive (≥50%). Extensive nonobstructive CAD was defined as plaque in all coronary arteries. Cox modeling assessed the association between CAD and the composite outcome of cardiovascular death, myocardial infarction, or stroke. RESULTS: Among 5,173 individuals, 53% were male, and 68% and 62% had hypertension and dyslipidemia, respectively. Individuals with obstructive CAD had a 71% higher risk of events (adjusted HR: 1.71; 95% CI: 1.21-2.42; P = 0.002) vs those with no CAD. At 4 years, event risks were 7.8% for obstructive CAD and 7.7% for extensive nonobstructive CAD, comparable to SELECT's control arm (9.7%). Applying SELECT's relative rate reduction of 20%, the number needed to treat was 66 for obstructive and 67 for extensive nonobstructive CAD, comparable to SELECT's 56. CONCLUSIONS: Obstructive or extensive nonobstructive CAD by CCTA identifies overweight/obese individuals without diabetes and no prior CVD as being at elevated cardiovascular risk, suggesting potential benefit from glucagon-like peptide-1 receptor agonist therapy.