Long-term stroke and major bleeding risk in patients with non-valvular atrial fibrillation: A comparative analysis between non-vitamin K antagonist oral anticoagulants and warfarin using a clinical data warehouse

Abstract

Introduction: Non-vitamin K antagonist oral anticoagulants (NOACs) has been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation (AF) since 2014. Many studies based on claim data revealed that NOACs had comparable effect to warfarin in preventing ischemic stroke with fewer hemorrhagic side effects. We analyzed the difference in clinical outcomes according to the drugs in patients with AF based on the clinical data warehouse (CDW). Methods: We extracted data of patients with AF from our hospital's CDW and obtained clinical information including test results. All claim data of the patients were extracted from National Health Insurance Service, and dataset was constructed by combining it with CDW data. Separately, another dataset was constructed with patients who could obtain sufficient clinical information from the CDW. The patients were divided NOAC and warfarin groups. The occurrence of ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, and death were confirmed as clinical outcome. The factors influencing the risk of clinical outcomes were analyzed. Results: The patients who were diagnosed AF between 2009 and 2020 were included in the dataset construction. In the combined dataset, 858 patients were treated with warfarin, 2,343 patients were treated with NOACs. After the diagnosis of AF, the incidence of ischemic stroke during follow-up was 199 (23.2%) in the warfarin group, 209 (8.9%) in the NOAC group. Intracranial hemorrhage occurred in 70 patients (8.2%) among the warfarin group, 61 (2.6%) of the NOAC group. Gastrointestinal bleeding occurred in 69 patients (8.0%) in the warfarin group, 78 patients (3.3%) in the NOAC group. NOAC's hazard ratio (HR) of ischemic stroke was 0.479 (95% CI 0.39–0.589, p < 0.0001), HR of intracranial hemorrhage was 0.453 (95% CI 0.31–0.664, p < 0.0001), and HR of gastrointestinal bleeding was 0.579 (95% CI 0.406–0.824, p = 0.0024). In the dataset constructed using only CDW, the NOAC group also had a lower risk of ischemic stroke and intracranial hemorrhage than warfarin group. Conclusions: In this CDW based study, NOACs are more effective and safer than warfarin in patients with AF even with long-term follow-up. NOACs should be used to prevent ischemic stroke in patients with AF