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RE-LY, ACTIVE offer options for reducing stroke risk in patients with AF
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Results from two trials examining the ability of antiplatelet therapy to reduce stroke risk in patients with atrial fibrillation suggested potential benefits from the treatments despite increased bleeding risk.
Results from several recent phase-3 trials presented by Stuart Connolly, MD, professor of medicine at McMaster University in Hamilton, Canada, suggested widening roles for anticoagulation therapy for the prevention of stroke when treating atrial fibrillation. Connolly presented results from the ACTIVE W and ACTIVE A trials (with emphasis on the results of ACTIVE A), as well as results from the RE-LY trial.
In the placebo-controlled ACTIVE A trial, researchers hypothesized that in patients with atrial fibrillation in whom warfarin (Coumadin, Bristol-Meyers Squibb) was unsuitable, the addition of clopidogrel (Plavix, Sanofi-Aventis) to aspirin would reduce the risk for major events with an acceptable risk for major bleeding. The ACTIVE A population included 7,554 patients with documented atrial fibrillation and one or more risk factors for stroke.
Patients assigned clopidogrel plus aspirin had a lower event rate for stroke over time compared with those assigned placebo (P=.00001). Patients assigned to clopidogrel plus aspirin had lower rates of ischemic/uncertain stroke (P < .001), with no difference in hemorrhagic stroke reported. Although warfarin remained the treatment of choice in high-risk patients with atrial fibrillation at the conclusion of the ACTIVE trial program despite an increase in the risk for hemorrhage, Connolly reported that clopidogrel plus aspirin in patients who were unsuitable for warfarin was associated with a 28% reduction in stroke.
“We typically pay this price with antithrombotic therapy, in that you get a greater antithrombotic effect but pay a price with increased bleeding,” Connolly said in his presentation. “The favorability of this trade-off using the therapy is almost always the question, and dabigatran may change that.”
Reduced ‘trade-off’ with dabigatran
Connolly also presented results of the RE-LY noninferiority trial, which included more than 18,000 patients with atrial fibrillation who had one or more risk factors for stroke. The researchers assigned patients either warfarin (n=6,022), 110-mg dabigatran (n=6,015) or 150-mg dabigatran (n=6,076). The high-dose dabigatran (Boehringer-Ingelheim) demonstrated superiority to warfarin (P< .001) for the reduction of stroke or systemic embolism, Connolly reported, and the low-dose dabigatran demonstrated noninferiority to warfarin but not superiority (P< .001).
The 150-mg dose of dabigatran was also associated with lower rates of ischemic/unspecified stroke vs. warfarin (P=.03), and both doses of dabigatran were associated with lower rates of hemorrhagic stroke vs. warfarin (P< .001 for both). Vascular mortality was reduced in the high-dose dabigatran group vs. warfarin (P=.04), and both doses of dabigatran were associated with lower rates of intracranial bleeding. The higher dose of dabigatran was associated with lower rates of stroke and systemic embolism (P=.005) and major hemorrhage (P=.05) vs. the low dose of dabigatran. The lower dose was associated with lower rates of major bleeding vs. warfarin (P=.003).
The results of the RE-LY trial suggested that dabigatran may be a promising anticoagulation therapy for many patients with atrial fibrillation, according to Connolly.
“Dabigatran appears to be an important new way to prevent stroke in atrial fibrillation, as both doses have clear advantages and are different from one another,” Connolly said. “Both doses reduce intracerebral and intracranial hemorrhage.”
For more information:
- Connolly S. Completed phase-3 trials of dabigatran and other agents (RE-LY, ACTIVE A, W & I) – Design, Results and Clinical Implications. Presented at: Boston Atrial Fibrillation Symposium; Jan. 14-16, 2010; Boston.