Expert Review: Thrombosis

Don’t use Dabigatran off-label with mechanical valves

Recently, several case reports have been published regarding the occurrence of mechanic valve thrombosis despite anticoagulation therapy with dabigatran etexilate (1,2). Dabigatran etexilate is an oral direct thrombin inhibitor that has recently been approved for anticoagulation of non-valvular atrial fibrillation (AF). While this medication possesses a number of characteristics that make it an attractive alternative to warfarin, its use for other indications currently remains untested.
Although in vitro and animal studies suggest that dabigatran for mechanical valve anticoagulation may be a potential therapeutic avenue (3,4) the recent reported treatment failures raise significant caution when using novel anticoagulants off-label.
Under the same notion, on 23th October 2012, the medical community has been informed that Boehringer Ingelheim has terminated one arm of a small phase II clinical trial (RE-ALIGN; NCT01452347) (5) exploring the safety of its oral anticoagulant dabigatran etexilate in patients with mechanical heart valves because of a possible increase in thromboembolic events at one or more of the dosages under study. In detail, RE-ALIGN utilizes dabigatran etexilate doses ranging from 150 to 300 mg twice daily, adjusted based on renal function and results of the Hemoclot assay in patients with mechanical heart valves. The dabigatran etexilate treatment had been allocated to two arms; patients started on their assigned oral anticoagulant at the time of surgery in one of the arms and more than three months after surgery in the other arm. The company reported that “interim analysis indicates that the studied dosing algorithm delivers lower-than-projected plasma levels of dabigatran in the post-surgery population, and an imbalance in reports of thromboembolic events (primarily strokes) has been identified”.

In conclusion, dabigatran etexilate has been approved only for patients who have non-valvular AF. However practicing physicians are starting off-label use because of the perceived convenience of the medication. On the contrary, recently published data suggest that off-label use of dabigatran etexilate is potentially harmful and should be prohibited.

Citation: Price J, Hynes M, Labinaz M, Ruel M, Boodhwani M. Mechanical valve thrombosis with dabigatran. J Am Coll Cardiol. 2012;60:1710-1

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