SAN ANTONIO—Dabigatran, an oral direct thrombin inhibitor, is as effective as warfarin in preventing subsequent stroke among patients with atrial fibrillation and prior transient ischemic attack (TIA) or stroke, and it was associated with a lower major hemorrhage rate, according to research presented at the 2010 International Stroke Conference.
“In patients who already had TIA or stroke and suffered from atrial fibrillation, dabigatran is as effective as warfarin,” reported Hans-Christoph Diener, MD, PhD. “It’s much easier to handle, because it’s given in a fixed oral dose and doesn’t require checking of anticoagulation. It has a significantly lower rate of cerebral and intracranial hemorrhage.” Dr. Diener is Professor and Chairman of the Department of Neurology at University Hospital in Essen, Germany.
The findings are based on a subset of 3,623 patients from the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial who received either warfarin or two blinded doses of dabigatran etexilate—110 mg or 150 mg—twice daily for a median of two years. All patients in the subanalysis had atrial fibrillation and a prior stroke or TIA. Overall, 18,113 patients with nonvalvular atrial fibrillation and moderate to high risk of stroke or systemic embolism were enrolled in RE-LY, which was conducted at 951 sites in 44 countries, including the United States. The primary results of RE-LY were published in the New England Journal of Medicine in 2009.
Subanalysis Results From RE-LY
In the subanalysis of patients with atrial fibrillation and prior stroke or TIA, 1,195 subjects received 110 mg of dabigatran, 1,233 received 150 mg of dabigatran, and 1,195 received warfarin. For the primary end point of incidence of ischemic stroke and systemic embolism, the researchers found no difference between the two doses of dabigatran and warfarin.
Among subjects who received warfarin, 64 events (rate of 2.74% per year) were observed, 55 events (2.32% per year) occurred in those who received 110 mg of dabigatran, and 51 (2.07% per year) events were reported in patients receiving the 150-mg dose of dabigatran. The relative risk reduction was 24% for participants taking 150 mg of dabigatran and 15% for those taking 110 mg of dabigatran, compared with those taking warfarin.
However, “in terms of major hemorrhagic complications, the low dose of dabigatran was significantly superior to warfarin, so it caused fewer major hemorrhages,” said Dr. Diener. “The high dose of dabigatran had an equivalent bleeding rate [to that of warfarin].
“What’s most important for neurologists is the risk of cerebral hemorrhage,” Dr. Diener commented. “Patients on warfarin had a higher risk for cerebral hemorrhage. Across the study period, patients who received warfarin had 18 hemorrhagic strokes, patients on low-dose dabigatran had two, and [those receiving the] high dose of dabigatran had five. This translates to a relative risk reduction of hemorrhagic stroke between 73% [for 150-mg dabigatran] and 89% [for 110-mg dabigatran].”
By comparison, in the overall results from RE-LY regarding stroke and systemic embolism, patients taking 150 mg of dabigatran had a 34% relative risk reduction and those taking 110 mg of dabigatran had a 9% relative risk reduction, compared with those taking warfarin.
“The results are in line with the overall study,” Dr. Diener told Neurology Reviews. “The fact that dabigatran was not superior to warfarin in the 150-mg bid dose was due to the smaller numbers.”
Among all patients in RE-LY regarding hemorrhagic stroke, those who took 150 mg dabigatran had a relative risk reduction of 74%, and those who took 110 mg of dabigatran had a 69% relative risk reduction, compared with those taking warfarin.
Myocardial Infarction and Intracranial Bleeding
Rates of myocardial infarction were similar among the three groups in the subanalysis. Patients taking the 110-mg dose of dabigatran had 15 events, those taking the 150-mg dose of dabigatran had 20 events, and those taking warfarin had 15 events. These rates were lower than the rates that were observed in the primary results from RE-LY, in which 71 myocardial infarctions were reported among subjects taking 110 mg of dabigatran, 69 in those taking 150 mg of dabigatran, and 48 in those taking warfarin.
In addition, among patients with prior stroke or TIA, six intracranial bleeding events were reported in subjects taking 110 mg of dabigatran, 13 events were observed in those taking 150 mg of dabigatran, and 30 events were reported in those taking warfarin. By comparison, in the primary results from RE-LY, 27 events were recorded among patients taking 110 mg of dabigatran, 36 in those taking 150 mg of dabigatran, and 87 in those taking warfarin.