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

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.

Pharmacologic Management for Ventricular Arrhythmias: Overview of Anti-Arrhythmic Drugs

“…Due to the similarity of its chemical structure, dronedarone has a similar mechanism of action to amiodarone through the blockade delayed rectifier potassium channel and increase in the ERP with subsequent decreased likelihood of reentry. However, the non-iodinated formulation subsequently has significantly lower rates of thyroid toxicity [ 100 ]. Initial studies have also found that dronedarone may have lower rates of pulmonary fibrosis, although hepatotoxicity rates are similar [ 100 , 101 ].…”

“…However, the non-iodinated formulation subsequently has significantly lower rates of thyroid toxicity [ 100 ]. Initial studies have also found that dronedarone may have lower rates of pulmonary fibrosis, although hepatotoxicity rates are similar [ 100 , 101 ]. To date, most large trials comparing amiodarone to dronedarone for efficacy have focused on atrial fibrillation management.…”