There was an increased risk for some bleeding events among patients with atrial fibrillation (AF) who received dronedarone in combination with a direct oral anticoagulant (DOAC). These findings were published in the American Journal of Cardiology.

Researchers sourced data from the Commercial Claims and the Medicare Supplemental databases of Truven Health MarketScan collected between 2007 and 2017. All new users of a DOAC who received a diagnosis of AF were included. Concomitant use of dronedarone was assessed for bleeding outcomes using a propensity score trimming methodology.

The final patient population comprised 51,420 users of apixaban and 1932 apixaban plus dronedarone, 42,312 users of dabigatran and 3117 dabigatran with dronedarone, and 57,300 users of rivaroxaban and 2395 users of rivaroxaban with dronedarone.

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Gastrointestinal (GI) bleeding events were most common and intracranial hemorrhage events least common.

Instances of GI bleeds were observed among dronedarone concomitant use with dabigatran (incidence rate ratio [IRR], 1.56; 95% CI, 1.14-2.14) and rivaroxaban (IRR, 1.55; 95% CI, 1.11-2.17) and bleeding at non-GI or non-intracranial sites with concomitant use with rivaroxaban (IRR, 1.51; 95% CI, 1.04-2.21).

There was a significant risk for GI bleeding for dabigatran concomitant use (adjusted hazard ratio [aHR], 1.40; 95% CI, 1.01-1.93; P =.04) and overall bleeding for rivaroxaban concomitant use (aHR, 1.31; 95% CI, 1.01-1.69; P =.04).

Risk for intracranial hemorrhage was not associated with dronedarone use with apixaban (aHR, 0.65; 95% CI, 0.16-2.64; P =.55), dabigatran (aHR, 1.14; 95% CI, 0.41-3.11; P =.81), or rivaroxaban (aHR, 0.75; 95% CI, 0.24-2.36; P =.63).

This study was limited by not having access to information about bleeding severity.

The data indicated that using cytochrome P450 3A4 inhibitors, such as dronedarone, concomitantly with DOACs increased instances of some bleeding events.

As the study authors noted, “this study highlights the need to increase awareness among healthcare professionals of the potentially increased risk of bleeding that may be associated when starting concomitant use of some DOACs and CYP3A4/Pgp inhibitors such as dronedarone, and the need to follow recommendations and closely monitor these patients after treatment initiation.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Gandhi SK, Reiffel JA, Boiron R, Wieloch M. Risk of major bleeding in patients with atrial fibrillation taking dronedarone in combination with a direct acting oral anticoagulant (from a US claims database). Am J Cardiol. 2021;159:79-86. doi:10.1016/j.amjcard.2021.08.015

This article originally appeared on The Cardiology Advisor