Predictors of Major Bleeding Among Working-Age Adults with Atrial Fibrillation: Evaluating the Effects of Potential Drug-drug Interactions and Switching from Warfarin to Non-vitamin K Oral Anticoagulants

Purpose: This study aims to evaluate the associations between switching from warfarin to non-vitamin K oral anticoagulants (NOACs), exposure to potential drug-drug interactions (DDIs), and major bleeding events in working-age adults with atrial fibrillation (AF). Methods: We conducted a retrospective cohort study using the claims database of commercially insured working-age adults with AF from 2010 to 2015. Switchers were defined as patients who switched from warfarin to NOAC; non-switchers were defined as those who remained on warfarin. We developed novel methods to calculate the number and proportion of days with potential DDIs with NOAC/warfarin. Multivariate logistic regressions were utilized to evaluate the associations between switching to NOACs, exposure to potential DDIs, and major bleeding events. Results: Among a total of 4126 patients with AF, we found a significantly lower number of potential DDIs and the average proportion of days with potential DDIs in switchers than non-switchers. The number of potential DDIs (AOR 1.14, 95% CI 1.02–1.27) and the HAS-BLED score (AOR 1.64, 95% CI 1.48–1.82) were significantly and positively associated with the likelihood of a major bleeding event. The proportion of days with potential DDIs was also significantly and positively associated with risk for bleeding (AOR 1.42, 95% CI 1.03, 1.96). We did not find significant associations between switching to NOACs and major bleeding events. Conclusions: The number and duration of potential DDIs and patients’ comorbidity burden are important factors to consider in the management of bleeding risk in working-age AF adults who take oral anticoagulants.