Key result
Dronedarone plus rivaroxaban is linked to ~31% higher major bleeding risk vs rivaroxaban alone.
Why the study?
Dronedarone may increase exposure and risk of major bleeding when prescribed with a DOAC, but the bleeding risk with their concomitant use in AF patients was unclear.
Cohort
Yes
Hazard Ratio: 1.31 (95% CI 1.01–1.69)
p-value: p=0.04
Dronedarone with DOACs may raise major bleeding risk in AF; leaves open need for prospective confirmation before practice change.
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.
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Gandhi et al. (2021) conducted a cohort in Atrial fibrillation. Dronedarone in combination with a DOAC (apixaban, dabigatran, or rivaroxaban) vs. DOAC alone was evaluated on First occurrence of major bleeding (hospitalization or emergency room visit for gastrointestinal bleeding, intracranial hemorrhage, or bleeding at other sites) (aHR 1.31, 95% CI 1.01-1.69, p=0.04). Concomitant use of dronedarone and rivaroxaban was associated with an increased risk of major bleeding compared to rivaroxaban alone (aHR 1.31; 95% CI 1.01-1.69; p=0.04), while no significant increase was seen with apixaban or dabigatran.
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