Clinical question: Is dabigatran, an oral thrombin inhibitor, an effective and safe alternative to warfarin in patients with atrial fibrillation?
Background: Warfarin reduces the risk of stroke among patients with atrial fibrillation (AF) but requires frequent laboratory monitoring. Dabigatran is an oral direct thrombin inhibitor given in fixed dosages without laboratory monitoring.
Study design: Randomized, multicenter, open-label, noninferiority trial.
Setting: 951 clinical centers in 44 countries.
Synopsis: More than 18,000 patients 65 and older with AF and at least one stroke risk factor were enrolled. The average CHADS2 score was 2.1. Patients were randomized to receive fixed doses of dabigatran (110 mg or 150 mg, twice daily) or warfarin adjusted to an INR of 2.0-3.0. The primary outcomes were a) stroke or systemic embolism and b) major hemorrhage. Median followup was two years.
The annual rates of stroke or systemic embolism for both doses of dabigatran were noninferior to warfarin (P<0.001); higher-dose dabigatran was statistically superior to warfarin (relative risk (RR)=0.66, P<0.001). The annual rate of major hemorrhage was lowest in the lower-dose dabigatran group (RR=0.80, P=0.003 compared with warfarin); the higher-dose dabigatran and warfarin groups had equivalent rates of major bleeding. No increased risk of liver function abnormalities was noted.
Bottom line: Dabigatran appears to be an effective and safe alternative to warfarin in AF patients. If the drug were to be FDA-approved, appropriate patient selection and cost will need to be established.
Citation: Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-1151.