The protective effect of obesity on mortality in acute coronary syndromes (ACS) patients remains debated. We aimed at evaluating the impact of obesity on ischemic and bleeding events as possible explanations to the obesity paradox in ACS patients. For the purpose of this substudy, patients enrolled in the START-ANTIPLATELET registry were stratified according to body mass index (BMI) into 3 groups: normal, BMI <25 kg/m2; overweight, BMI: 25 to 29.9 kg/m2; obese, BMI ≥30 kg/m2. The primary end point was net adverse clinical end points (NACE), defined as a composite of all-cause death, myocardial infarction, stroke, and major bleeding. In n = 1,209 patients, n = 410 (33.9%) were normal, n = 538 (44.5%) were overweight and n = 261 (21.6%) were obese. Compared to the normal weight group, obese and overweight patients had a higher prevalence of cardiovascular risk factors but were younger, with a better left ventricular ejection fraction and lower PRECISE-DAPT score. At 1-year follow-up net adverse clinical endpoints was more frequently observed in normal than in overweight and obese patients (15.1%, 8.6%, and9.6%, respectively; p = 0.004), driven by a significantly higher rate of all-cause death (6.3%, 2.6%, and 3.8%, respectively; p = 0.008), whereas no significant differences were noted in terms of myocardial infarction, stroke, and major bleeding. When correcting for confounding variables, BMI loses its power in independently predicting outcomes, failing to confirm the obesity paradox in a real-world ACS population. In conclusion, our study conflicts the obesity paradox in real-world ACS population, and suggest that the reduced rate of adverse events and mortality in obese patients may be explained by relevant differences in the clinical risk profile and medications rather than BMI per se.
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