Dabigatran not superior to aspirin for recurrent stroke prevention in certain patients
The industry-funded multicenter randomized, double-blind trial compared dabigatran, 150 mg or 110 mg twice daily, with aspirin, 100 mg once daily, in patients who had had an embolic stroke of undetermined source.
Dabigatran was not superior to aspirin for prevention of recurrent stroke in patients with a history of embolic stroke of undetermined source, according to a new industry-funded study.
Researchers performed a multicenter randomized, double-blind trial comparing dabigatran, 150 mg or 110 mg twice daily, with aspirin, 100 mg once daily, in patients who had had an embolic stroke of undetermined source. Patients ages 60 years and older were eligible if their stroke had occurred within the previous three months, or within the previous six months if they had at least one vascular risk factor. Patients ages 18 to 59 years were eligible if their stroke occurred within the previous three months and they had at least one additional vascular risk factor. The lower dabigatran dose was used in patients who were ages 75 years and older or had impaired renal function.
The study's primary outcome and primary safety outcome were recurrent stroke and major bleeding, respectively. Median follow-up was 19 months. The results of the study, which was funded by Boehringer Ingelheim, were published May 16 by the New England Journal of Medicine.
Overall, 5,390 patients at 564 sites in 42 countries were enrolled in the study. Patients' mean age was 64.2 years; 36.9% were women. A total of 2,695 patients were assigned to dabigatran, and 2,695 were assigned to aspirin. During follow-up, 177 patients in the dabigatran group and 207 patients in the aspirin group had recurrent stroke of any type (6.6% vs. 7.7%, respectively; rates per year, 4.1% vs. 4.8%). The hazard ratio was 0.85 (95% CI, 0.69 to 1.03; P=0.10). One hundred seventy-two patients in the dabigatran group and 203 patients in the aspirin group had ischemic stroke (4.0% per year vs. 4.7% per year, respectively; hazard ratio, 0.84 [95% CI, 0.68 to 1.03]).
Seventy-seven patients in the dabigatran group (1.7% per year) experienced major bleeding versus 64 (1.4% per year) in the aspirin group (hazard ratio, 1.19; 95% CI, 0.85 to 1.66), while clinically relevant nonmajor bleeding was seen in 70 patients and 41 patients, respectively (1.6% and 0.9% per year). Intracranial hemorrhage occurred in 32 patients (1.2%) in each group, for a rate of 0.7% per year (hazard ratio, 1.73; 95% CI, 1.17 to 2.54).
The researchers noted that they based their study on a hypothesis that dabigatran would outperform aspirin in patients with this type of stroke because many of them may have had an unrecognized cardiac embolism. Post hoc analysis suggested a possible effect of dabigatran on stroke recurrence after a year, but no conclusions can be drawn from that, the authors said. They determined that based on their results, dabigatran was not superior to aspirin for prevention of recurrent stroke in patients with a history of embolic stroke of undetermined source. Rates of major bleeding were similar in both groups, but clinically relevant nonmajor bleeding events were more common in patients taking dabigatran, the authors said.