Drug-drug interactions of NOACs with comedication: Prevalence and implications for adverse events in patients with atrial fibrillation.

BACKGROUND: The clinical relevance of drug-drug interactions associated with non‒vitamin K-antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) remains poorly understood. OBJECTIVE: We evaluated the prevalence of pharmacokinetic and pharmacodynamic drug-drug interactions and their association with adverse clinical outcomes in patients with AF receiving NOACs. METHODS: We analyzed patients from the prospective, multicenter Swiss-AF cohort study. We used frailty survival models to investigate the association of the different potential interactions with the respective clinical adverse outcomes (major bleeding, clinically relevant non-major bleeding, any bleeding, ischemic stroke or systemic embolism). RESULTS: Our analysis comprised 1732 patients with AF (mean age 73 ± 8 years, 501 [29%] women) with a median follow-up period of 6 years. For 683 of these patients (39%), we recorded ≥1 potential drug-drug interaction. In the multivariable adjusted model, the hazard ratio of drug-drug interaction was 1.21 (95% confidence interval [CI] 0.84-1.75, P = .31) for major bleeding, 1.22 (95% CI 0.92-1.62, P = .17) for clinically relevant nonmajor bleeding, 1.22 (95% CI 0.97-1.54, P = .09) for any bleeding, and 1.00 (95% CI 0.22-4.53, P = .99) for ischemic stroke or systemic embolism. CONCLUSION: In a large real-world cohort of patients with AF, the prevalence of potential interactions of long-term comedication with NOACs was high. We found no strong evidence of an association between these interactions and an increased risk of bleeding or the composite outcome ischemic stroke or systemic embolism. REGISTRATION: Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02105844. CLINICALTRIALSGOV IDENTIFIER: NCT02105844.