Safety of Dabigatran in Acute Ischemic Stroke Patients with Microbleeds: Post Hoc Analysis of DATAS-II Randomized Trial

Background: Cerebral microbleeds are associated with an increased risk of hemorrhagic transformation (HT) following acute ischemic stroke. We investigated whether the effect of dabigatran (vs. aspirin) in patients with acute minor non-cardioembolic ischemic stroke/transient ischemic attack (TIA) is modified by baseline microbleeds on MRI. Methods: The Dabigatran Treatment of Acute Stroke II trial randomized 305 patients with acute minor non-cardioembolic ischemic stroke/TIA to dabigatran (150/110 mg twice daily) or aspirin (81 mg daily) for 30 days. Microbleeds were centrally adjudicated in patients with an interpretable blood-sensitive sequence on baseline MRI. In this post hoc analysis, we used multivariable regression models to determine the association between microbleeds and any incident HT on day-30 MRI and excellent functional outcome (modified Rankin scale = 0-1) at 90 days. Results: A total of 251 (82.3%) participants (mean age = 66 +/- 13 years, 36% women, median [IQR] onset-to-randomization time = 40[27-55] hours; median [IQR] NIHSS = 1 [0-2]) were included, of whom 82 (33%) had microbleeds. On day-30 MRI, 6% (n = 14) developed HT, and 80% (n = 191) achieved 90-day mRS of 0-1. We found no association between microbleed presence and HT (adjusted OR = 0.84; 95%CI:0.21-3.25) or excellent functional outcome (adjusted RR = 1.09; 95%CI:0.94-1.26). The rate of HT in patients with microbleeds was 3% with dabigatran and 4% with aspirin (OR = 0.85; 95%CI:0.11-6.75). Excellent functional outcome occurred in 74% and 84% of dabigatran and aspirin-treated patients, respectively (RR = 0.88; 95%CI:0.69-1.12). The presence, severity or location of microbleeds did not modify the effect of dabigatran on these outcomes (p-interaction > 0.05). Conclusions: Early dabigatran treatment appears safe in patients with acute minor non-cardioembolic ischemic stroke/TIA and hemorrhage-prone cerebral small vessel disease marked by microbleeds on MRI.