Comparing the Effectiveness and Safety of Nonvitamin K Antagonist Oral Anticoagulants and Warfarin in Elderly Asian Patients With Atrial Fibrillation: A Nationwide Cohort Study

Background: Stroke prevention in elderly patients with atrial fibrillation (AF) can be challenging, requiring a balance between thromboembolism prevention and serious bleeding. Comparisons of nonvitamin K antagonist oral anticoagulants (NOACs) and warfarin in older adults at different age strata (65-74, 75-89, and ≥ 90 years of age) in the daily practice have not been well described, particularly in Asians. We aimed to assess the clinical outcomes of NOACs compared with warfarin for stroke prevention in elderly patients with AF. Methods: From 2012 to 2015, 64,169 patients ≥ 65 years of age with AF who received at least one NOAC (dabigatran, rivaroxaban, or apixaban) or warfarin prescription were identified from the Taiwan National Health Insurance Research Database. The risks of ischemic stroke, intracranial hemorrhage (ICH), major bleeding, mortality, and composite adverse events were compared between NOACs and warfarin in all patients ≥ 65 years of age and, specifically, with different age strata (ie, 65-74, 75-89, ≥ 90 years). Results: Overall, NOACs were associated with a significantly lower risk of ischemic stroke (adjusted hazard ratio [aHR], 0.869; 95% CI, 0.812-0.931), ICH (aHR, 0.524; 95% CI, 0.456-0.601), major bleeding (aHR, 0.824; 95% CI, 0.776-0.875), mortality (aHR, 0.511; 95% CI, 0.491-0.532), and composite adverse events (aHR, 0.646; 95% CI, 0.625-0.667) than warfarin. There was heterogeneity in treatment effect for NOACs vs warfarin in different age strata, but the results still favored NOACs even among very older adults (≥ 90 years). The results were generally consistent with propensity matching analysis. The absolute risk difference and reductions in ICH and composite adverse events with NOAC use were even greater among older adults than warfarin. Conclusions: Compared with warfarin, NOACs were associated with a significantly lower risk of adverse events, with heterogeneity in treatment effects among different age strata. Overall, the clear safety signal in favor of NOACs over warfarin was evident irrespective of age strata, being most marked in very older adults.