Combination of Rivaroxaban and Amiodarone Increases Bleeding in Patients With Atrial Fibrillation.

Background: Rivaroxaban and amiodarone are commonly used for treating patients with atrial fibrillation. Drug-drug interactions between rivaroxaban and amiodarone may increase exposure to rivaroxaban. However, the clinical relevance of this drug-drug interaction is still not clear.

Objective: The aim was to investigate the risk of bleeding in patients receiving a combination of rivaroxaban and amiodarone.

Methods: This was a prospective observational study in which we included atrial fibrillation patients treated with rivaroxaban. The patients were divided into the rivaroxaban group and the combination of rivaroxaban and amiodarone group (the combination group). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust between-group differences. The primary endpoint was defined as the time to the first occurrence of a composite of major, clinically relevant nonmajor, and minor bleeding.

Results: In total, 481 atrial fibrillation patients were included in the analysis. After PSM, 154 patients in the rivaroxaban group were matched with 154 patients in the combination group. The bleeding events mainly consisted of clinically relevant nonmajor and minor bleeding. Only one patient experienced major bleeding. The primary outcome was recorded in 26.0% of patients in the combination group and 10.4% of patients in the rivaroxaban group (hazard ratio = 2.76, 95% CI = 1.55-4.93, P < 0.001). The bleeding risk was significantly higher in the combination group compared with that in the rivaroxaban group in the IPTW and stabilized IPTW analyses (hazard ratio = 2.17, 95% CI = 1.32-3.56, P = 0.002).

Conclusion and relevance: The combination of rivaroxaban and amiodarone increased the risk of bleeding in patients with atrial fibrillation, especially clinically relevant nonmajor and minor bleeding. Physicians prescribing rivaroxaban and amiodarone together should be concerned about an increase in the risk of nonmajor bleeding.