Patterns and Outcomes of Novel Oral Anticoagulants in Real-World Patients with Non-Valvular Atrial Fibrillation

Background: Novel oral anticoagulants (NOACs) recently launched to Taiwan for preventing ischemic stroke among non-vavluar atrial fibrillation patients. However, the effectiveness and safety in real-world clinical practice is still scarce, especially in Asian population. Objective: First, to analyze the prescription patterns of oral antithrombotic agents after the launch of NOACs. Second, to assess the effectiveness and safety between patients who newly initiated NOAC and warfarin among Asian population. Third, we aim to evaluate whether being long-term prescribed warfarin would affect the effectiveness and safety of NOAC. Methods: We used National Health Insurance Research Database (NHIRD) to assess non-valvular atrial fibrillation patients who prescribed dabigatran, rivaroxaban, or warfarin from Jun 1st, 2012 to Dec 31th, 2015. We applied propensity score matching to the Cox proportional hazard model to evaluate the effectiveness and safety between NOACs (including dabigatran and rivaroxaban) and warfarin. The analyses were also repeated to assess different drug groups, dose groups, and elderly patients with at least 65 or 80 years old. The follow-up period was the time from index date to the outcome of interests, switching to or discontinuation of alternative oral anticoagulants, end of the administrative period. Results: Compared with warfarin in the warfarin-naive stratum, NOAC were generally associated with a lower risk of intracranial hemorrhage (HR: 0.45, 95% CI: 0.31-0.66), venous thromboembolism (HR: 0.37, 95% CI: 0.21-0.66), and the composite bleeding events (HR: 0.8, 95% CI: 0.69-0.92), whereas there were no significant differences in 3 the risk of gastrointestinal bleeding. In different dose groups, rivaroxaban 20 mg and 15 mg were associated with a lower risk of ischemic stroke compared with warfarin (HR:0.48, 95%: 0.29-0.80 and HR: 0.69, 95% CI: 0.53-0.90 in rivaroxaban 20 mg and 15 mg, respectively), and rivaroxaban 20 mg was associated with a lower risk of gastrointestinal bleeding (HR:0.47, 95% CI: 0.24-0.90). In elderly, rivaroxaban was associated with lower risk of ischemic stroke compared with warfarin in patients with at least 65 years old (HR: 0.71, 95% CI: 0.56-0.89) and 80 years old (HR: 0.65, 95% 0.46-0.61). In warfarin-experienced stratum, NOAC was associated with lower risk of intracranial hemorrhage (HR: 0.38, 95% CI: 0.19-0.78). However, there were no significant differences in the risk of ischemic stroke, transient ischemic attack, venous thromboembolism, and gastrointestinal bleeding. Conclusions: In the ─real-world∥ clinical practice, NOACs were generally associated with a lower risk of intracranial hemorrhage compared with warfarin. Rivaroxaban with a dose equal to or greater than 15 mg may be considered as a sufficient therapeutic dose in preventing thromboembolism events. Moreover, rivaroxaban was found to be a better choice than warfarin in preventing ischemic stroke among elderly patients.