Dabigatran and other novel oral anticoagulants are effective and safe for reducing thromboembolic risk in the setting non-valvular AF.  However, it remains unclear whether these newer anticoagulants are as effective as warfarin for reducing thromboembolic complications among patients with mechanical heart valves.  As oral anticoagulation is a mainstay of therapy in patients with mechanical valves, this is a critical question as it relates to potential expanded indications for dabigatran use.

The Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients after Heart Valve Replacement (RE-ALIGN) sought to validate a regimen of dabigatran to prevent thromboembolic complications from mechanical heart valves. Patients with either mechanical aortic or mitral valves were randomized to dabigatran or warfarin. Dabigatran dosing was guided by renal function and plasma trough levels.  Warfarin was adjusted by INR with target range determined by thromboembolic risk.  The trial was stopped early after recruitment of 252 patients out of a planned 405 when an interim analysis revealed a large excess of both thromboembolic and bleeding episodes in patients randomized to dabigatran. In the dabigatran group, 9 patients (5%) suffered non-haemorrhagic strokes and 5 (3%) had valve thrombosis, compared to no stroke or valve thrombosis event among patients on warfarin.  Furthermore, major bleeding was twice as common in the dabigatran group.

Conclusions

In this phase II study, dabigatran failed to demonstrate efficacy or safety in comparison to warfarin for anticoagulation in patients with mechanical heart valves.  As both thrombotic and bleeding events were higher with dabigatran, there appears little promise that revised dosing regimens with dabigatran could achieve outcomes equivalent to those seen with warfarin. This study also highlights the potential for harm when clinical benefits from one setting (non-valvular atrial fibrillation) are extrapolated to another (mechanical heart valves).  For this reason, warfarin should remain the anticoagulant of choice for mechanical heart valves until further safety and efficacy trials of novel anticoagulants are completed.

•  Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, Blatchford J, Devenny K, Friedman J, Guiver K, Harper R, Khder Y, Lobmeyer MT, Maas H, Voigt JU, Simoons ML and Van de Werf F. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013 Sep 26;369(13):1206-14.