Efficacy and Safety of Dronedarone in Overweight and Obesity: Post Hoc Analysis of the ATHENA Trial.

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 ( < 25 kg/m²), overweight (25-30 kg/m²), and obese ( > 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 < 25 kg/m², 43% (n = 1996) had BMI 25-30 kg/m², and 32% (n = 1489) 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.