Drug-drug interactions in atrial fibrillation patients receiving direct oral anticoagulants

Polypharmacy is common in patients with atrial fibrillation (AF), making these patients vulnerable to the occurrence of potential drug-drug interactions (DDIs). We assessed the risk of ischemic stroke and major bleeding in the context of concomitant treatment with potential DDIs in patients with AF prescribed direct oral anticoagulants (DOACs). Using the common data model (CDM) based on an electronic health record (EHR) database, we included new users of DOACs from among patients treated for AF between January 2014 and December 2017 (n = 1938). The median age was 72 years, and 61.8% of the patients were males, with 28.2% of the patients having a CHA(2)DS(2)-VASc score in category 0–1, 49.4% in category 2–3, and 22.4% in category ≥ 4. The CHA(2)DS(2)-VASc score was significantly associated with ischemic stroke occurrence and hospitalization for major bleeding. Multiple logistic regression analysis showed that increased risk of ischemic stroke and hospitalization for major bleeding was associated with the number of DDIs regardless of comorbidities: ≥ 2 DDIs was associated with ischemic stroke (OR = 18.68; 95% CI, 6.22–55.27, P < 0.001) and hospitalization for major bleeding (OR = 5.01; 95% CI, 1.11–16.62, P < 0.001). DDIs can cause reduced antithrombotic efficacy or increased risk of bleeding in AF patients prescribed DOACs.