Dabigatran After Embolic Stroke of Undetermined Source

Study Questions:

After embolic stroke of undetermined source (ESUS), is rivaroxaban or aspirin better for secondary stroke prevention?


RE-SPECT ESUS was a large, multicenter, double-blind trial of patients with ESUS who were randomized 1:1 to aspirin or dabigatran. ESUS was defined as a nonlacunar stroke without specific cause in a patient with: 1) no extra- or intracranial stenosis ≥50% in arteries supplying the area of infarct, 2) no atrial fibrillation >6 minutes on ≥20 hours of rhythm monitoring, and 3) no intracardiac thrombus on transthoracic echocardiography or transesophageal echocardiography. The primary outcome was recurrent ischemic stroke or hemorrhagic stroke. The primary safety outcome was major bleeding.


A total of 5,390 patients were randomized (2,695 in each group) with a mean age of 64 years and a median duration of follow-up of 19 months (interquartile range, 13-27). High rates of drug discontinuation were observed in both groups (24.9% in the dabigatran group and 21.1% in the aspirin group). Recurrent stroke occurred in 177 patients (6.6%) in the dabigatran group and in 207 patients (7.7%) in the aspirin group (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.69-1.03). Major bleeding occurred in 77 patients (2.9%) in the dabigatran group and 64 patients (2.4%) in the aspirin group (HR, 1.19; 95% CI, 0.85-1.66).


No difference in recurrent ischemic or hemorrhage stroke or in major bleeding was observed for ESUS patients on dabigatran versus aspirin.


Many stroke neurologists suspected that empiric anticoagulation with a novel oral anticoagulant (NOAC) would improve outcomes in patients with ESUS, given the positive safety profile of NOACs and the possibility of undetected atrial fibrillation or other nonspecific embolic risk factors in ESUS patients. The results of this study, coupled with the results of NAVIGATE ESUS trial (aspirin vs. rivoraxaban; N Engl J Med 2018;378:2191-2201), significantly dampens the enthusiasm among stroke neurologists for empiric use of anticoagulation for secondary stroke prevention in patients with ESUS. Antiplatelet monotherapy remains first-line therapy in ESUS patients.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Noninvasive Imaging, Prevention, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Echocardiography/Ultrasound

Keywords: Anticoagulants, Aspirin, Atrial Fibrillation, Brain Ischemia, Constriction, Pathologic, Echocardiography, Transesophageal, Embolism, Hemorrhage, Risk Factors, Secondary Prevention, Stroke, Thrombosis, Vascular Diseases

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