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Vitamin K antagonist exposure not linked with dabigatran, warfarin outcomes in RE-LY patients
Ezekowitz M. Circulation. 2010;122:2246-2253.
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Vitamin K antagonist exposure did not influence the outcome of two different doses of dabigatran when compared with warfarin among patients with atrial fibrillation, results from an analysis of the RE-LY study indicated.
Researchers of the RE-LY trial tested two doses of dabigatran (Pradaxa, Boehringer Ingelheim) — 110 mg or 150 mg twice daily — against warfarin (Coumadin, Bristol-Myers Squibb) in a population of vitamin K antagonist-naive and vitamin K antagonist-experienced patients with AF (total n=18,113).
Study data indicated that among vitamin K antagonist-naive patients, rates of stroke and systemic embolism were 1.57% per year for dabigatran 110 mg, 1.07% for 150 mg and 1.69% for warfarin. Despite comparable rates between 110-mg dabigatran and warfarin (P=.65), dabigatran at 150 mg was superior to the staple drug (P=.005). Similarly, stroke systemic and embolism rates in vitamin K antagonist-experienced patients did not differ between 110-mg dabigatran and warfarin (P=.32) but did differ in the 150-mg dose (P=.007).
Major bleeding rates also favored both doses of dabigatran but only reached statistical significance among patients given dabigatran at 110 mg in the vitamin K antagonist-experienced arm (P=.003). However, intracranial bleeding rates were significantly lower for both doses of dabigatran when compared with warfarin for vitamin K antagonist-naive and vitamin K antagonist-experienced patients.
“It was believed that patients who were vitamin K antagonist-experienced were likely to do better than patients who are new to anticoagulation because they have demonstrated the ability to comply with an anticoagulation regimen, they have a personalized dose of warfarin that achieves a therapeutic INR, and they have passed the ‘vitamin K antagonist stress test,’ thereby reducing the chance of uncovering major sources of bleeding,” the researchers wrote. “This report found that dabigatran, the novel direct thrombin inhibitor, was better than the comparator warfarin for both vitamin K antagonist-naive and -experienced patients and therefore could be used clinically in both cases.”
The major observation from this sub-study of the RE-LY trial demonstrates that both patients starting dabigatran without prior vitamin K antagonism experience and those switching to dabigatran from a vitamin K antagonism (warfarin) exposure benefit from dabigatran at either dose compared with warfarin. So whether or not patients have previously been anticoagulated with warfarin, they can still benefit from this direct thrombin inhibitor.
The original trial showed that dabigatran at a dose of 110 mg was not inferior and at a dose of 150 mg was superior to warfarin for prevention of stroke and systemic embolism. Importantly, bleeding rates were lower for 110 mg and similar for 150 mg compared with warfarin, whereas intracranial bleeding rates were lower for both dabigatran doses. The remaining question to answer will be whether dabigatran is superior or equivalent to rivaroxaban, a factor Xa inhibitor, shown in the ROCKET AF trial to be noninferior to warfarin on an intention-to-treat analysis and superior in an on treatment analysis in patients with higher CHADS risk scores than in RE-LY.
– Douglas Zipes, MD
Cardiology Today Arrhythmia Disorders Section Editor
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