The use of vitamin K antagonists provides excellent protection against thromboembolic complications in patients with mechanical valves, however long-term INR monitoring is needed. Dabigatran is an oral direct thrombin inhibitor which was shown to be effective in patients with atrial fibrillation. Based on these promising results this study was designed to evaluate its use in patients with mechanical heart valves.
It was a prospective and randomized phase 2 study of two populations: patients with mechanical aortic or mitral valves in the last 7 days and those who had undergone the implant in the last 3 months or more.
The patients were randomized in a 2:1 ratio to receive dabigatran or warfarin. The initial dose of dabigatran (150, 220 or 300 mg 2 times per day) was chosen based on kidney function and adjusted to obtain a plasma concentration of more or less 50 ng/ml. Warfarin doses were adjusted to reach an INR of 2 to 3 or 2.5 to 3.5 according to thromboembolic risk. The end points were stroke, systemic thromboembolism, transient stroke, bleeding, venous thromboembolism, myocardial infarction and death. The study was suspended early after including 252 patients due to an excess of bleeds and thromboembolic events in the dabigatran group.
Adjustment to the dose or discontinuation of the drug was necessary in 52 of the 162 dabigatran patients (32%). Nine strokes (5%) were observed in the dabigatran group vs none in the warfarin group, major bleeding 4% vs 2%, asymptomatic thrombosis of the valve 3% vs 0% respectively. All the major bleedings were pericardial.
Conclusion:
The use of dabigatran in patients with mechanical heart valves was associated with an increased risk of thromboembolic complications and bleeding compared to warfarin.
Editorial comment:
Possible explications for these results could be that the majority of the patients (80%) had undergone surgery recently or that the dabigatran was not effective in suppressing clotting on the artificial surface of the mechanical valves.
Frans Van de Werf
2013-09-02
Original title: RE-ALIGN: Dabigatran in patients with a mechanical heart valve.
