Dabigatran etexilate for thromboembolic prophylaxis in non-valvular atrial fibrillation: the RE-LY study and substudies with commentary

Abstract

In 2010, dabigatran etexilate, a direct thrombin inhibitor, was the first new oral anticoagulant to be approved for thromboembolic prophylaxis in atrial fibrillation in over 50 years. Dabigatran, unlike warfarin, has a short half-life with a rapid onset of anticoagulant effect, does not require dose adjustment or monitoring, and does not interact with food. The RE-LY trial compared two doses of dabigatran (110 and 150 mg twice daily) with adjusted dose warfarin in patients with non-valvular atrial fibrillation and at least 1 stroke risk factor. Compared with warfarin, dabigatran 150 mg twice daily was superior in reducing the risk of stroke or systemic embolism and was associated with a similar rate of major bleeding, while dabigatran 110 mg twice daily was equally effective in reducing stroke or systemic embolism and was associated with less major bleeding. Despite these favorable results, there remains disagreement regarding the optimal dose and overall safety of dabigatran in certain patient populations including the elderly and those with renal dysfunction.

Keywords::

• anticoagulation
• atrial fibrillation
• dabigatran
• direct thrombin inhibitor
• RE-LY
• stroke
• thromboembolism
• warfarin

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Dabigatran is a new oral direct thrombin inhibitor which has been approved for thromboembolic prophylaxis in non-valvular atrial fibrillation. It is the first oral anticoagulant approved for this indication since the introduction of warfarin and other similar drugs over 50 years ago.

• • Dabigatran is administered as a fixed dose and does not require routine blood monitoring or dose adjustment.

• • In the RE-LY study, dabigatran 110 mg twice daily was equally effective to warfarin in reducing the risk of stroke or systemic embolism with a reduction in major bleeding. Dabigatran 150 mg twice daily was more effective than warfarin in reducing the risk of stroke or systemic embolism with a similar risk of major bleeding.

• • The 110 mg dose of dabigatran is only available in Europe despite a favorable safety profile among patients who are elderly and with moderate renal dysfunction. The 75 mg dose of dabigatran which was approved in the USA for use in patients with severe renal dysfunction was not studied in a randomized clinical trial.