ASSOCIATION OF CORONARY ARTERY DISEASE WITH CARDIOVASCULAR OUTCOMES IN OBESITY WITHOUT DIABETES: IMPLICATIONS FOR THE USE OF CORONARY CTA TO IDENTIFY SELECT TRIAL-LIKE POPULATION

Abstract

Therapeutic Area: Obesity Background: The SELECT trial demonstrated GLP1RA's significant reduction in cardiovascular (CV) events in individuals with preexisting cardiovascular disease (CVD) and overweight/obesity but without diabetes. Coronary CT angiography (CCTA) identifies presence and severity of coronary artery disease (CAD). We hypothesized that patients with significant CAD detected by CCTA, but no prior CVD, meeting other SELECT trial inclusion criteria, may have similar risk as those with established CVD in the trial. We aimed to evaluate the association between CAD by CCTA and CV outcomes among patients without known coronary heart disease who otherwise resemble the SELECT trial population. Methods: We included individuals aged ≥45, body mass index (BMI) ≥27, undergoing clinically indicated CCTA (2006-2021) at 2 large academic centers. Exclusion criteria comprised prior myocardial infarction (MI), coronary revascularization, end-stage chronic kidney disease, and life-limiting cancer. To mirror the SELECT trial population, patients diagnosed with diabetes at baseline were excluded. CAD severity was categorized based on the Coronary Artery Disease Reporting and Data System 2.0 (CAD-RADS) as absent (CAD-RADS 0), non-obstructive (1-49% stenosis, CAD-RADS 1-2) or obstructive (≥ 50%, CAD-RADS 3-5). Cox hazard modeling assessed the association between CAD severity and the primary composite outcome (same as SELECT trial) of CV death, MI, or stroke. Results: A total of 4,065 patients were included, median age 59 years (IQR 52-67); 53.7% males. Hypertension and dyslipidemia were present in 71.6% and 66.1%, respectively, and 8.5% had a BMI ≥ 40. CAD was absent in 30.3%, while 46.8% had nonobstructive CAD and 22.9% had obstructive CAD. Overweight/obese patients with nonobstructive and obstructive CAD had significantly higher risk of the primary composite outcome than those without CAD (Logrank p < 0.001) (Figure 1). The event rate over a mean 3.3-year follow-up was 2.9% for non-obstructive CAD and 7.1% for obstructive CAD (comparable to SELECT's control arm rate of 8.0%). Conclusions: The presence of obstructive CAD on CCTA may help identify overweight/obese individuals at elevated risk for adverse cardiovascular outcomes who could potentially benefit from GLP1RA therapy.