Risk of Major Bleeding in Patients With Atrial Fibrillation Taking Dronedarone in Combination With a Direct Acting Oral Anticoagulant (From a U.S. Claims Database).

Dronedarone may increase exposure and the risk of major bleeding when prescribed with a direct oral anticoagulant (DOAC). This retrospective cohort study examined the risk of the first occurrence of major bleeding (hospitalization or emergency room visit for gastrointestinal [GI] bleeding, intracranial hemorrhage [ICH], or bleeding at other sites) among new users of apixaban, dabigatran, and rivaroxaban in patients with AF ≥18 years (January 1, 2007 to September 30, 2017) from the United States Truven Health MarketScan claims, comparing concomitant users of dronedarone to DOAC alone users in patients with atrial fibrillation (AF). No increased risk of major bleeding was associated with use of dronedarone and apixaban (adjusted Hazard Ratio [aHR]: 0.69 [95% confidence interval [CI]: 0.40, 1.17], p = 0.16), a modestly increased risk of GI bleeding but not overall bleeding was associated with use of dronedarone and dabigatran (aHR bleeding: 1.18 [95% CI: 0.89, 1.56], p = 0.26; aHR GI bleeding: 1.40 [95% CI: 1.01, 1.93]; p = 0.04) and an increased risk of overall bleeding, driven by GI bleeding, was associated with use of dronedarone and rivaroxaban (aHR bleeding: 1.31 [95% CI: 1.01, 1.69]; p = 0.04; aHR GI bleeding: 1.39 [95% CI: 0.98, 1.95]; p = 0.06), compared to each DOAC respectively. There was no increased risk of ICH associated with combined use of dronedarone and any DOAC. Prospective analyses, preferably randomized controlled studies, are needed to further explore the risk of major bleeding with concomitant use of DOACs and CYP3A4/P-gp inhibitors such as dronedarone.