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

J Cardiovasc Electrophysiol. 2026 May;37(5):969-979. doi: 10.1111/jce.70322. Epub 2026 Mar 22.

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 ( < 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.

Keywords: ATHENA; antiarrhythmic drug; atrial fibrillation; body mass index; dronedarone; obesity.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Amiodarone* / adverse effects
  • Amiodarone* / analogs & derivatives
  • Amiodarone* / therapeutic use
  • Anti-Arrhythmia Agents* / adverse effects
  • Anti-Arrhythmia Agents* / therapeutic use
  • Atrial Fibrillation* / diagnosis
  • Atrial Fibrillation* / drug therapy
  • Atrial Fibrillation* / mortality
  • Body Mass Index
  • Double-Blind Method
  • Dronedarone
  • Female
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Obesity* / complications
  • Obesity* / diagnosis
  • Obesity* / mortality
  • Overweight* / complications
  • Overweight* / diagnosis
  • Overweight* / mortality
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Dronedarone
  • Anti-Arrhythmia Agents
  • Amiodarone

Associated data

  • ClinicalTrials.gov/NCT00174785
  • ClinicalTrials.gov/NCT00174785
  • ClinicalTrials.gov/NCT00174785

Grants and funding