Impact of Drug Interactions on Major Bleed Rates in Patients Taking Direct Oral Anticoagulants

Abstract

Background: While direct oral anticoagulants (DOACs) have less stringent monitoring, favorable pharmacokinetics, and fewer drug interactions compared to warfarin, there is still a potential for drug–drug interactions. There is limited evidence showing total impact of DOAC drug interactions on major bleeding events. Methods: This was an IRB-approved retrospective, case control, single center study. Patients were included if they had received a DOAC from January 2012 to September 2019 and were identified for major bleeding events and matched to a control group. The primary objective was to compare the presence of major drug interactions between patients on DOACs who did and did not have a major bleeding event. The secondary objectives were to compare the impact of specific interacting drug classes and their additive effects on major bleeding events. Results: There were 122 patients included in the study. While the number of patients on at least one interacting medication within duration of DOAC use was numerically higher in the bleed group (85% vs 72%), this was not significant (P = .077). There were significantly more patients on at least three interacting medications within the last 3 months of the study period in the bleed group (n = 9 vs 1), with significantly higher use of aspirin (n = 38 vs 17) and rate control agents (n = 24 vs 11). Conclusion: There may be a cumulative effect on risk of bleeding if patients are on three or more interacting medications concomitantly with a DOAC. This risk of bleeding may be higher with aspirin and rate control agents.