A 110 mg or 150 mg dose of dabigatran showed similar outcomes to warfarin for stroke or systemic embolism in patients who experienced a previous incidence of stroke or transient ischemic attack, according to a sub-analysis of the RE-LY trial published online Nov. 7 in Lancet Neurology.
“In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, dabigatran reduced occurrence of both stroke and hemorrhage compared with warfarin in patients who had atrial fibrillation and were at increased risk of stroke,” the authors wrote.
To study the adverse effects when dabigatran (Pradaxa, Boehringer Ingelheim Pharmaceuticals) was administered to patients with previous stroke or transient ischemic attack, Hans-Christoph Diener, MD, PhD, of the University Hospital Essen, in Essen, Germany, and colleagues used data from the RE-LY trial that randomized 18,113 atrial fibrillation patients to receive either 110 mg or 150 mg doses of dabigatran twice daily or warfarin that was adjusted to international normalized ratio (2.0 to 3.0).
The substudy’s primary endpoint was stroke or systemic embolism, while the primary safety endpoint was major hemorrhage.
Of the 18,113 patients from the RE-LY trial, 2,273 had a previous stroke, 1,663 had a previous transient ischemic attack and 313 experienced both.
Diener et al found that the rate of stroke or systemic embolism was higher in patients who experienced a previous stroke or transient ischemic attack compared to those who did not: 171 of the 3,623 patients who experienced prior events versus 348 of the 14,489 patients who did not.
Within the aforementioned subgroup of patients who experienced stroke or transient ischemic attack, 1,195 patients were administered a 110 mg dose of dabigatran, 1,233 were administered 150 mg of dabigatran and 1,195 were administered warfarin.
The primary endpoint occurred in 65 patients administered warfarin compared to 55 patients administered the 110 mg dose of dabigatran and 51 patients administered the 150 mg dose of dabigatran.
Diener and colleagues found that bleeding incidence occurred less frequently in the patients administered 110 mg doses of dabigatran, but were similar for patients administered 150 mg doses of dabigatran and those given warfarin.
“The higher dose lowered intracranial bleeding but increased the rate of gastrointestinal bleeding compared with warfarin,” the authors noted. “Among patients with previous stroke or transient ischemic attack, the 110 mg dabigatran group had a lower mortality rate than the warfarin group, but because there was no significant interaction between death from any cause and previous stroke or transient ischemic attack, we cannot conclude that there is a true benefit on mortality with the 110 mg dose compared with warfarin in this population.
“In choosing the dose of dabigatran, physicians need to trade off the benefits of stroke prevention against the risk of hemorrhage. In general, strokes are more severe than are major hemorrhages and have more substantial long-term consequences,” the authors noted.
Additionally, they concluded that a 150 mg dose of dabigatran twice daily could be the preferred method of treatment compared to 110 mg twice daily because of its potential to reduce the risk of ischemic stroke without increasing a patient’s risk of hemorrhagic stroke.
"Because of the necessary trade-off between stroke prevention and bleeding with both doses of dabigatran, consultation with patients regarding their preferences for treatment dose will be even more important to ascertain their threshold for stroke prevention over increased bleeding risk or vice versa," wrote Deirdre A. Lane, MD, and Gregory YH. Lip, MD, PhD, in an accompanying editorial.
The study was funded by Boehringer Ingelheim.