The direct thrombin inhibitor dabigatran can be used in atrial fibrillation patients as an alternative to warfarin, according to updated guidelines from the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society. The update was published online Feb. 14 in Circulation.
[Dabigatran, Rivaroxaban Vie as Warfarin Alternatives]
The guideline writing committee, which issued a focused update in December (Circulation 2011;123:104-23), noted that the approval of dabigatran by the Food and Drug Administration in October 2010 occurred too late for consideration.
The update to the guidelines summarizes the evidence supporting the FDA approval of dabigatran etexilate to prevent stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In the RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy) trial – a noninferiority study of 18,113 patients with nonvalvular atrial fibrillation and at least one other risk factor for stroke – 150 mg of dabigatran twice daily reduced the risk of all types of stroke or systemic embolism by 34%. The average age of the patients in the study was 71 years.
Two dosing regimens (110 mg twice daily or 150 mg twice daily) were evaluated, and the 110-mg dose of dabigatran was noninferior to warfarin for the prevention of stroke or systemic embolism. The 110-mg dose of dabigatran was associated with significantly lower rates of major bleeding than was warfarin, and the rate of major bleeding at the 150-mg dose was noninferior to warfarin. Myocardial infarction was more common in dabigatran patients compared with warfarin patients, but the difference was not significant. The 110-mg dosage was not approved, however; the dosage for all patients except those with severe renal impairment is 150 mg twice daily.
Dr. L. Samuel Wann, a cardiologist at Wheaton Franciscan Healthcare in Wauwatosa, Wis., and chair of the 2011 Writing Group, and colleagues noted that dabigatran is not the best choice for all patients, given the twice-daily dosing regimen and increased risk of side effects. However, patients with atrial fibrillation and at least one additional risk factor for stroke might benefit from dabigatran depending on factors including cost, patient preferences, ability to comply with twice-daily dosing, and availability of an anticoagulation management program to help with routine maintenance, the reviewers wrote (Circulation 2011 Feb. 14 [doi:10.1161/CIR.0b013e31820f14c0]).
[FDA Panel Votes to Approve Dabigatran for Reduction of Stroke Risk]
Dr. Wann had no financial conflicts to disclose. Several of the writing group members disclosed serving as a speaker or consultant for, or receiving research funding from, multiple pharmaceutical companies including Medtronic, Boston Scientific, AstraZeneca, Sanofi-Aventis, and GlaxoSmithKline, as well as Boehringer Ingelheim, which markets dabigatran as Pradaxa.