The increased risk of bleeding due to drug-drug interactions in patients administered direct oral anticoagulants

Abstract

IntroductionDirect oral anticoagulants (DOACs) have the potential to increase bleeding due to drug-drug interactions (DDIs). In the present study, the risk of bleeding was evaluated when drugs with potential DDIs were simultaneously prescribed with DOACs. Materials and methodsThe present study included patients with non-valvular atrial fibrillation (AF) and venous thromboembolism (VTE) who were newly prescribed DOACs between January 2014 and December 2016. ResultsThe study included 115,362 patients with AF or VTE who were newly administered DOACs (median age, 73 years, range, 19–108 years; males, 53.0%; AF, 81.9%). A total of 7001 any bleeding (6.1%) and 2283 major bleeding (2.0%) events occurred with DOAC prescriptions. Based on multiple logistic regression analysis, the number of DDIs was significantly associated with bleeding events independent of CHA2DS2-VASc score and Charlson Comorbidity Index (CCI). The rates of exposure to DDI drugs associated with any bleeding and major bleeding were 56.7% and 66.1%, respectively. The most common DDI drugs showed similar distributions in any or major bleeding; non-steroidal anti-inflammatory drugs (NSAIDs), antiplatelet agents, diltiazem, and amiodarone were frequently prescribed. ConclusionsPhysicians prescribing DOACs for AF or VTE should be aware of the increasing risk of bleeding associated with drugs having potential DDIs regardless of comorbidities.