Safety and efficacy of dronedarone in overweight and obesity: a post-hoc analysis of the ATHENA trial

Abstract Background Obesity, a prevalent condition with multiple comorbidities including atrial fibrillation (AF), presents challenges in pharmacological management due to limited data on optimal drug dosing in this population. Dronedarone, an antiarrhythmic drug (AAD), has demonstrated efficacy in patients with AF and cardiovascular (CV) risk factors; however, its performance across different body mass index (BMI) categories is not well understood. Purpose To evaluate the efficacy and safety of dronedarone across various BMI categories in patients with AF. Methods A post hoc analysis of the ATHENA trial (NCT00174785), a randomized, double-blind trial of dronedarone versus placebo, was conducted across the following BMI categories: normal or underweight (BMI <25 kg/m²), overweight (BMI 25–30 kg/m²), and obese (BMI >30 kg/m²). The primary outcome was time to first CV hospitalization or death from any cause, analyzed using the log-rank test and Cox regression. Results Of the 4,628 patients randomized in the ATHENA trial, 25% (n=1,143) were normal or underweight, 43% (n=1,996) were overweight, and 32% (n=1,489) were obese. Dronedarone significantly reduced the risk of first CV hospitalization or death across all BMI groups, with hazard ratios (HR) ranging from 0.639 (95% CI 0.524–0.780) to 0.818 (95% CI 0.691–0.968) compared to placebo, with no interaction effect by BMI (p=0.142). Risk of first hospitalization due to AF recurrence was similarly lower in all BMI groups with dronedarone versus placebo. All-cause mortality was significantly reduced in normal-weight patients (HR 0.551, 95% CI 0.353–0.861, p=0.009), while serious treatment-emergent adverse events (TEAEs) showed no correlation with increasing BMI. TEAEs leading to discontinuation were more frequent in the dronedarone group and primarily gastrointestinal in origin. Conclusion Dronedarone is an effective AAD for patients with AF across a wide range of BMI categories, reducing the risk of hospitalization and death, with a manageable safety profile.Risk of first CV hosp. or death