Risk of interstitial lung disease in patients treated for atrial fibrillation with dronedarone versus other antiarrhythmics

Pharmacoepidemiol Drug Saf. 2021 Oct;30(10):1353-1359. doi: 10.1002/pds.5233. Epub 2021 May 4.


Purpose: To compare risks of interstitial lung disease (ILD) between patients treated with dronedarone versus other antiarrhythmics.

Methods: Parallel retrospective cohort studies were conducted in the United States Department of Defense Military Health System database (DoD) and the HealthCore Integrated Research Database (HIRD). Study patients were treated for atrial fibrillation (AF) with dronedarone, amiodarone, sotalol, or flecainide. Propensity score matching was employed to create analysis cohorts balanced on baseline variables considered potential confounders of treatment decisions. The study period of July 20, 2008 through September 30, 2014 included a 1-year baseline and minimum 6 months of follow-up, for patients with drugs dispensed between July 20, 2009 and March 31, 2014. Suspect ILD outcomes were reviewed by independent adjudicators. Cox proportional hazards regression compared risk of confirmed ILD between dronedarone and each comparator cohort. A sensitivity analysis examined the effect of broadening the outcome definition.

Results: A total 72 ILD cases (52 DoD; 20 HIRD) were confirmed among 27 892 patients. ILD risk was significantly higher among amiodarone than dronedarone initiators in DoD (HR = 2.5; 95% CI = 1.1-5.3, p = 0.02). No difference was detected in HIRD (HR = 1.0; 95% CI = 0.4-2.4). Corresponding risks in sotalol and flecainide exposure groups did not differ significantly from dronedarone in either database.

Conclusions: ILD risk among AF patients initiated on dronedarone therapy was comparable to or lower than that of amiodarone initiators, and similar to that of new sotalol or flecainide users. This finding suggests that elevated ILD risk associated with amiodarone does not necessarily extend to dronedarone or other antiarrhythmic drugs.

Keywords: amiodarone; antiarrhythmia agents; atrial fibrillation; dronedarone; interstitial; lung diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Arrhythmia Agents / adverse effects
  • Atrial Fibrillation* / drug therapy
  • Atrial Fibrillation* / epidemiology
  • Dronedarone
  • Humans
  • Lung Diseases, Interstitial* / chemically induced
  • Lung Diseases, Interstitial* / epidemiology
  • Retrospective Studies
  • United States / epidemiology


  • Anti-Arrhythmia Agents
  • Dronedarone