Association of Ischemic Stroke, Major Bleeding, and Other Adverse Events With Warfarin Use vs Non-vitamin K Antagonist Oral Anticoagulant Use in Patients With Atrial Fibrillation With a History of Intracranial Hemorrhage

Importance Current guidelines recommend the use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation (AF). Data regarding warfarin sodium use compared with NOAC use in patients with AF with a history of intracranial hemorrhage (ICH) are limited. Objective To compare the clinical outcomes of warfarin use and NOAC use in patients with AF with a history of ICH using a nationwide cohort with AF. Design, Setting, and Participants A nationwide cohort study from January 1, 2012, to December 31, 2016, was performed using data from the Taiwan National Health Insurance Research Database. The dates of analysis were July 1 to September 1, 2019. The study population comprised patients with AF with a history of ICH and a CHA(2)DS(2)-VASc score (congestive heart failure, hypertension, age >= 75 years [doubled], diabetes, prior stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease], age 65-74 years, sex category [female]) of at least 1 for men or at least 2 for women who had received warfarin or NOACs. The clinical outcomes were examined using Cox proportional hazards regression analyses among the study population before and after propensity score matching. Exposures Oral anticoagulation with warfarin or NOACs. Main Outcomes and Measures The clinical outcomes measured were all-cause mortality, ischemic stroke, ICH, major bleeding, and adverse events. Results The study cohort included 4540 patients (mean [SD] age, 76.0 [10.5] years; 2653 men [58.4%]), with 1047 patients receiving warfarin (mean [SD] age, 75.1 [11.4] years; 571 men [54.5%]) and 3493 patients receiving NOACs (mean [SD] age, 76.3 [10.2] years; 2082 men [59.6%]). Compared with warfarin use, NOAC use was associated with statistically significantly lower risk of all-cause mortality (adjusted hazard ratio [aHR], 0.517; 95% CI, 0.457-0.585), ICH (aHR, 0.556; 95% CI, 0.389-0.796), and major bleeding (aHR, 0.645; 95% CI, 0.525-0.793), whereas the rate of ischemic stroke was similar in the 2 groups (aHR, 0.879; 95% CI, 0.678-1.141). These results were generally consistent after propensity score matching among 973 patients in each group. Conclusions and Relevance Among patients with AF with prior ICH, NOAC use was associated with lower rates of ICH and major bleeding compared with warfarin use, whereas the rate of ischemic stroke was similar in the 2 groups. Among patients with AF with prior ICH, NOACs could be the preferred choice for stroke prevention. This cohort study in Taiwan compares the clinical outcomes of warfarin use and non-vitamin K antagonist oral anticoagulant use in patients with atrial fibrillation with a history of intracranial hemorrhage using a nationwide cohort with atrial fibrillation. Question Are non-vitamin K antagonist oral anticoagulants (NOACs) associated with greater clinical benefit than warfarin sodium among patients with atrial fibrillation with a history of intracranial hemorrhage? Findings In this cohort study, 4540 patients were identified with prior intracranial hemorrhage who received warfarin or NOACs. The use of NOACs was associated with statistically significantly lower rates of all-cause mortality, intracranial hemorrhage, and major bleeding compared with the use of warfarin, whereas the rate of ischemic stroke was similar in the 2 groups. Meaning Among patients with atrial fibrillation with prior intracranial hemorrhage, NOACs could be the preferred choice for stroke prevention.