Early Rivaroxaban Use After Cardioembolic Stroke May Not Result in Hemorrhagic Transformation

Patients with atrial fibrillation who have suffered a transient ischemic attack (TIA) or ischemic stroke are at high risk for recurrence and require long-term anticoagulation. The optimal timing of anticoagulation after an ischemic stroke is controversial. Although anticoagulation in acute stroke patients is associated with reduced early stroke recurrence rates, these benefits are offset by a comparable increase in the rate of symptomatic hemorrhagic transformation (HT). Rivaroxaban is a non–vitamin K antagonist oral anticoagulant (NOAC) used to prevent ischemic stroke in atrial fibrillation patients. All safety data related to rivaroxaban come from trials that excluded patients ≤14 days after stroke and 3 days after TIA. The primary aim of this prospective study was to assess the rate of magnetic resonance imaging (MRI)– detected HT associated with initiating rivaroxaban therapy ≤14 days after cardioembolic stroke/TIA. Methods This was an investigator-initiated prospective, open-label, single-arm study (NCT 02279940). Patients with documented nonvalvular atrial fibrillation and acute TIA or moderate ischemic stroke (National Institute of Health Stroke Scale [NIHSS] <9) were enrolled. Patients were approached for study participation after the treating physician’s decision to treat with rivaroxaban ≤14 days after stroke/TIA. Patients with estimated glomerular filtration rate <30 mL/min or contraindications to MRI were excluded. The research protocol was approved by our local Human Research Ethics Board. The dose of rivaroxaban was determined based on renal function (estimated glomerular filtration rate 30–50 mL/min:15 mg daily, estimated glomerular filtration rate >50 mL/min:20 mg daily). Study participants were followed for 90 days after rivaroxaban initiation. NIHSS score was assessed at baseline, day 7, and day 90. All patients had an MRI at baseline (≤24 hours from study recruitment) and 7±2 days after enrollment. Day-7 MRI assessors had access to baseline scans. The volume of ischemic diffusion-weighted imaging (DWI) lesions were measured planimetrically (Analyze 12.0, Biomedical Imaging Resource, Rochester). HT was graded Background and Purpose—Early anticoagulation after cardioembolic stroke remains controversial because of the potential for hemorrhagic transformation (HT). We tested the safety and feasibility of initiating rivaroxaban ≤14 days after cardioembolic stroke/transient ischemic attack. Methods—A prospective, open-label study of patients with atrial fibrillation treated with rivaroxaban ≤14 days of transient ischemic attack or ischemic stroke (National Institute of Health Stroke Scale <9). All patients underwent magnetic resonance imaging <24 hours of rivaroxaban initiation and day 7. The primary end point was symptomatic HT at day 7. Results—Sixty patients (mean±SD age 71±19 years, 82% stroke/18% transient ischemic attack) were enrolled. Median (interquartile range) time from onset to rivaroxaban was 3 (5) days. At treatment initiation, median National Institute of Health Stroke Scale was 2 (4), and median diffusion-weighted imaging volume was 7.9 (13.7) mL. At baseline, HT was present in 25 (42%) patients (hemorrhagic infarct [HI]1=19, HI2=6). On follow-up magnetic resonance imaging, no patients developed symptomatic HT. New asymptomatic HI1 developed in 3 patients, and asymptomatic progression from HI1 to HI2 occurred in 5 patients; otherwise, HT remained unchanged at day 7. Conclusions—These data support the safety of rivaroxaban initiation ≤14 days of mild–moderate cardioembolic stroke/ transient ischemic attack. Magnetic resonance imaging evidence of petechial HT, which is common, does not appear to increase the risk of symptomatic HT. (Stroke. 2016;47:1917-1919. DOI: 10.1161/STROKEAHA.116.013491.)