Dabigatran versus Warfarin in Patients with Mechanical Heart Valves

JW Eikelboom, SJ Connolly, M Brueckmann, CB Granger, Arie-Pieter Kappetein, MJ Mack, J Blatchford, K Devenny, J Friedman, K Guiver, R Harper, Y Khder, MT Lobmeyer, H Maas, JU Voigt, Maarten Simoons, F van der Werf

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Abstract

BackgroundDabigatran is an oral direct thrombin inhibitor that has been shown to be an effective alternative to warfarin in patients with atrial fibrillation. We evaluated the use of dabigatran in patients with mechanical heart valves. MethodsIn this phase 2 dose-validation study, we studied two populations of patients: those who had undergone aortic- or mitral-valve replacement within the past 7 days and those who had undergone such replacement at least 3 months earlier. Patients were randomly assigned in a 2:1 ratio to receive either dabigatran or warfarin. The selection of the initial dabigatran dose (150, 220, or 300 mg twice daily) was based on kidney function. Doses were adjusted to obtain a trough plasma level of at lea ResultsThe trial was terminated prematurely after the enrollment of 252 patients because of an excess of thromboembolic and bleeding events among patients in the dabigatran group. In the as-treated analysis, dose adjustment or discontinuation of dabigatran was required in 52 of 162 patients (32%). Ischemic or unspecified stroke occurred in 9 patients (5%) in the dabigatran group and in no patients in the warfarin group; major bleeding occurred in 7 patients (4%) and 2 patients (2%), respectively ConclusionsThe use of dabigatran in patients with mechanical heart valves was associated with increased rates of thromboembolic and bleeding complications, as compared with warfarin, thus showing no benefit and an excess risk. (Funded by Boehringer Ingelheim; ClinicalTrials.gov numbers, NCT01452347 and NCT01505881.) In a phase 2 trial, patients with mechanical heart valves were randomly assigned to receive either dabigatran or warfarin for anticoagulation. Dabigatran was associated with higher rates of ischemic stroke (5%, vs. 0% with warfarin) and major bleeding (4% vs. 2%). Prosthetic heart-valve replacement is recommended for many patients with severe valvular heart disease and is performed in several hundred thousand patients worldwide each year.(1) Mechanical valves are more durable than bioprosthetic
Original languageUndefined/Unknown
Pages (from-to)1206-1214
Number of pages9
JournalNew England Journal of Medicine
Volume369
Issue number13
DOIs
Publication statusPublished - 2013

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