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| |  Betrixaban Shows Advantages Over Warfarin Among High-Risk Patients With AF: Presented at ACC By Walter Alexander ATLANTA -- March 19, 2010 -- In high-risk patients with atrial fibrillation (AF), stroke prophylaxis with betrixaban, an investigational oral factor Xa inhibitor, may entail similar or lower risks for serious bleeding than conventional therapy with warfarin, researchers said here at the 59th Annual Scientific Sessions of the American College of Cardiology (ACC). The finding emerged from the international, phase 2 study of the safety, tolerability and pilot efficacy of oral factor Xa inhibitor betrixaban compared with warfarin (EXPLORE-Xa), which included patients with AF regardless of renal function, age, weight, or need for other medications. Betrixaban offers several potential advantages over warfarin. It does not require monitoring and has minimal renal excretion (<5%), obviating dose adjustments for renal impairment. In addition, since it is not metabolised by the CYP450 system, major drug interactions are not expected, according to Michael D. Ezekowitz, MD, Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, and Jefferson Medical College, Philadelphia, Pennsylvania. “An antidote for betrixaban is being co-developed, which makes it unique among these agents,” he said on March 15 during a Late-Breaking Clinical Trial presentation. EXPLORE-Xa compared safety and tolerability of 3 betrixaban doses (40, 60, and 80 mg once-daily) with dose-adjusted warfarin in 506 patients (median age, 74 y) with nonvalvular atrial fibrillation or atrial flutter and at least 1 additional risk factor for stroke. Patients were randomly assigned to the 4 study arms with 127 in each group. The primary endpoint was time to major and clinically relevant non-major bleeding. After a median follow-up of 147 days, there were fewer reports of major bleeding and clinically relevant non-major bleeding among patients taking betrixaban 40 mg daily as compared with those taking warfarin (1 patient vs 4 patients). With the 60- and 80-mg betrixaban daily doses, bleeding rates (5 patients and 4 patients, respectively) were similar with those in the warfarin group. There was 1 death in each of the treatment groups.
“It’s my view, based on the evidence, that all of the doses of the drug are active, and there is a suggestion of a dose-response that will have to be verified in much larger trials,” said Dr. Ezekowitz during a press conference. “Generally, the drug was well tolerated. Only 1 patient withdrew from therapy because of gastrointestinal side effects.” D-dimer, a measurement of the activity of the anticoagulation system that increases directly with thrombotic activity, went down from baseline consistently as the betrixaban dose went from 40 to 80 mg. “What appeals to me about this drug is that it’s oral and once-daily, it requires no dose adjustments for renal impairment, and it will have an antidote for someone who would need quick reversal, [which] is in development,” said the moderator of the press conference and ACC president, Ralph Brindis, MD, University of California, San Francisco, San Francisco, California. [Presentation title: A Phase 2, Randomized, Parallel Group, Dose-Finding, Multicenter, Multinational Study of the Safety, Tolerability and Pilot Efficacy of Three Blinded Doses of the Oral Factor Xa Inhibitor Betrixaban Compared With Open-Label Dose-Adjusted Warfarin in Patients With Non-Valvular Atrial Fibrillation (EXPLORE-Xa). Late-Breaking Clinical Trials II]
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