Dabigatran vs. Aspirin for Secondary Prevention After Embolic Stroke of Undetermined Source - Japanese Subanalysis of the RE-SPECT ESUS Randomized Controlled Trial

Background: The international Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the EfficaCy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate versus Acetylsalicylic Acid in Patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) trial did not demonstrate superiority of dabigatran over aspirin for reduction of recurrent strokes in patients with embolic strokes of undetermined source (ESUS). Based on pre-defined subanalyses, the safety and efficacy of dabigatran vs. aspirin in Japanese patients was assessed.

Methods and results: ESUS patients were randomized to receive either dabigatran (150 or 110 mg twice daily) or aspirin (100 mg once daily). Of 5,390 patients randomized, 594 were Japanese. Most Japanese patients (99.8%) underwent brain magnetic resonance imaging for trial screening, compared to 76.8% of non-Japanese (P<0.0001). In the Japanese cohort, over a 19.4-month median follow-up period, recurrent stroke as the primary outcome occurred in 20/294 patients (4.3%/year) in the dabigatran group and 38/300 (8.3%/year) in the aspirin group (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.32-0.94). Major bleeding occurred in 12 patients (2.5%/year) and 17 patients (3.5%/year), respectively (HR, 0.72; 95% CI, 0.34-1.52). In contrast, in the non-Japanese cohort, recurrent stroke occurred in 4.1%/year and 4.3%/year, respectively, showing no apparent difference in recurrent stroke for dabigatran vs. aspirin (HR, 0.91; 95% CI, 0.74-1.14). The P-interaction for treatment and region did not reach statistical significance (P=0.09).

Conclusions: Dabigatran was putatively associated with a lower relative risk of recurrent stroke compared with aspirin in Japanese ESUS patients.