Anticoagulation Protocol for Secondary Prevention of Acute Ischemic Stroke Associated with Nonvalvular Atrial Fibrillation

•High risk of acute ischemic recurrence prior to anticoagulation initiation.•Days to treatment initiation, severity, and HAS-BLED correlated with recurrence.•No correlations with CHADS2, CHA2DS2-VASc.•No subsequent intracranial hemorrhage within 90 days.•Consideration of severity, rt-PA, reperfusion/hemorrhage for safety and efficacy.•OAC timing for stroke secondary prevention. There is no clear evidence regarding when to initiate oral anticoagulants (OACs) for secondary prevention of recurrent stroke in patients with atrial fibrillation (AF). Therefore, this study aimed to evaluate the safety and efficacy of a novel OAC initiation protocol for secondary prevention of acute ischemic stroke associated with AF. In this multicenter prospective study 597 consecutive Japanese patients with acute ischemic stroke associated with nonvalvular AF received post-stroke OACs according to a protocol based on severity (clinical (NIHSS) and radiological (ASPECTS + W)), rt-PA use, reperfusion, and hemorrhagic transformation (HT). Primary outcomes of safety and efficacy, including symptomatic hemorrhage, cerebral stroke, and disability were evaluated at 14 and 90 days. Mean OAC initiation time was 2.60±2.14 days from onset. The shortest and longest mean initiation times were 0.47±0.50 and 6.16±0.72 days, respectively. Following OAC administration, no ICH was observed within 90 days. A significantly higher incidence of acute recurrent ischemic events occurred 14 days prior to OAC (4.7%) compared with chronic recurrence within 90 days (0.8%) (P = 0.00013, McNemar's test) . Recurrence prior to OAC use was significantly correlated with days to treatment (P = 0.00224), severity (NIHSS, ASPECTS+W: P = 0.0223, P = 0.0393, respectively), and HAS-BLED (P = 0.0395) and there were no correlations with CHADS2 (P = 0.277) or CHA2DS2-VASc (P = 0.246) (Wilcoxon rank sum-test). This comprehensive OAC initiation protocol was relatively safe and effective for secondary prevention of stroke in patients with AF. Risk of acute recurrence was high, indicating that OACs should be started as early as possible. (clinical trial registration number: 15B 128)