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

Arlene Tave, Earl Goehring, Vibha Desai, Chuntao Wu, Rhonda L Bohn, Sally G Tamayo, Nicholas Sicignano, Juhaeri Juhaeri, Judith K Jones, Sheila R Weiss, Arlene Tave, Earl Goehring, Vibha Desai, Chuntao Wu, Rhonda L Bohn, Sally G Tamayo, Nicholas Sicignano, Juhaeri Juhaeri, Judith K Jones, Sheila R Weiss

Abstract

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.

Conflict of interest statement

Ms. Tave, Mr. Goehring, Dr. Desai, Dr. Bohn, Dr. Jones and Dr. Weiss declare that they have no conflicts of interest. Dr. Wu was employed by Sanofi at the time of conducting this study. Dr. Juhaeri is a Sanofi employee. Dr. Tamayo is a retired member of the US military; this work was prepared as part of her official duties. Mr. Sicignano is an employee of Health ResearchTx.

© 2021 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Hazard ratios and 95% confidence intervals of confirmed incident ILD in PS‐matched analysis datasets during follow‐up for new users of other antiarrhythmic medications relative to dronedarone: DoD database primary analysis, HIRD database, and DoD database sensitivity analysis—July 20, 2009 to September 30, 2014. * P < 0.05; Hazard ratio is adjusted for study year of index date. † Hazard ratio is adjusted for age on index date

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