ABSTRACT Introduction Obesity represents a prevalent condition with multiple comorbidities, including atrial fibrillation (AF). Dronedarone, an antiarrhythmic drug (AAD), has demonstrated efficacy in patients with paroxysmal/persistent AF and cardiovascular (CV) risk factors. We aimed to evaluate the efficacy and safety of dronedarone in patients with AF across body mass index (BMI) categories. Methods and Results A post hoc analysis of data from the randomized, double‐blind ATHENA trial (NCT00174785), which compared dronedarone with placebo, was conducted across the following BMI categories: normal/underweight ( 30 kg/m²). The primary outcome was time to first CV hospitalization or death from any cause. Treatment‐emergent adverse events (TEAEs) were also assessed. Of 4628 patients, 25% ( n = 1143) had BMI 30 kg/m². Compared with placebo, dronedarone significantly reduced the risk of first CV hospitalization or death across all BMI groups with hazard ratios (HRs) ranging from 0.639 (95% confidence interval CI 0.524–0.780) to 0.818 (95% CI 0.691–0.968); no interaction by BMI was noted ( p = 0.142). Risk of first hospitalization due to AF recurrence was lower in all BMI groups with dronedarone. All‐cause mortality was significantly reduced in normal/underweight patients (HR 0.551 95% CI 0.353–0.861), but not in those who had overweight (HR 0.976 95% CI 0.655–1.453) or obesity (HR 1.184 95% CI 0.742–1.889)(p for interaction=0.048). Incidences of serious TEAEs showed no apparent association with increasing BMI. TEAEs leading to discontinuation (primarily gastrointestinal) were more frequent with dronedarone. Conclusion Dronedarone is an effective AAD for patients with AF across a range of BMI categories with a manageable safety profile. Trial Registration: NCT00174785
Vámos et al. (Sun,) studied this question.