Dabigatran Versus Warfarin in Patients With Mechanical Heart Valves

Study Questions:

What is the effectiveness of dabigatran in patients with mechanical heart valves?


In RE-ALIGN, a phase 2 dose-validation study, the investigators 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 least 50 ng/ml. The warfarin dose was adjusted to obtain an international normalized ratio of 2-3 or 2.5-3.5 on the basis of thromboembolic risk. The primary endpoint was the trough plasma level of dabigatran.


The 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 nine patients (5%) in the dabigatran group and in no patients in the warfarin group; major bleeding occurred in seven patients (4%) and two patients (2%), respectively. All patients with major bleeding had pericardial bleeding.


The authors concluded that the use of dabigatran in patients with mechanical heart valves was associated with increased rates of thromboembolic and bleeding complications, as compared with warfarin.


The results of this study indicate that dabigatran was not as effective as warfarin for the prevention of thromboembolic complications in patients with mechanical heart valves, and was associated with an increased risk of bleeding. Study findings suggest that dabigatran is not appropriate as an alternative to warfarin for the prevention of thromboembolic complications in patients who require anticoagulation after the implantation of a prosthetic heart valve, and should not be used for that purpose. Antithrombotic agents that are effective for stroke prevention in patients with atrial fibrillation may not necessarily be useful in patients with mechanical heart valves because the mechanisms of thrombosis are different.

Keywords: Stroke, Benzimidazoles, Warfarin, Heart Valves

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