Non-Vitamin K Antagonist Oral Anticoagulant Drug-Drug Interactions in Patients with Atrial Fibrillation Using Dronedarone and Non-Dronedarone Antiarrhythmic Drugs

Introduction: Non-vitamin K antagonist oral anticoagulant (NOAC) do not normally require INR-monitoring. We aimed to investigate drug-drug interactions of NOACs in patients with atrial fibrillation (AF) using antiarrhythmic drugs. Hypothesis: Dronedarone may have less drug-drug interaction compared to non-dronedarone antiarrhythmic drugs. Methods: National Health Insurance Research Database were retrieved between 2012 and 2017 for patients with AF. We excluded patients not taking antiarrhythmic drugs, bradycardia, heart block, history of heart failure, mitral stenosis, prosthetic valve, incomplete demographic data, and follow-up <3 months. Primary outcomes were major bleeding, intracranial hemorrhage, and gastrointestinal bleeding. Results: In total, 84,933 patients used NOAC in patients with AF were enrolled. After exclusion criteria, there were 26,773 patients with 204,937 person-quarters remained for analysis after the exclusion criteria were applied In terms of major bleeding, there was no increased major bleeding due to DDI between NOAC and dronedarone (adjusted rate ratio [aRR]: 0.77, 99% confidence interval [CI]: 0.54-1.12, p = 0.074). In terms of intracranial hemorrhage, there was no increased major bleeding due to DDI between NOAC and dronedarone (aRR: 0.64, 99% CI: 0.34-1.20, p = 0.0668). In terms of gastrointestinal bleeding, there was no increased major bleeding due to DDI between NOAC and dronedarone (aRR: 0.86, 99% CI: 0.55-1.35, p = 0.3819). Conclusions: In this study, NOACs and dronedarone coprescription is not associated with an increased risk of major bleeding, intracranial hemorrhage, nor gastrointestinal bleeding. The results suggest that such NOAC with dronedarone coprescription should be practiced in place of NOAC with amiodarone when the clinical criteria are appropriate.