Dabigatran versus warfarin in patients with atrial fibrillation," by Stuart J. Connelly, et al., New England Journal of Medicine, 361(12): 1139-51, 17 September 2009.
[Authors' affiliations: 12 institutions worldwide]
Abstract: "Background Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor.
Methods In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran—110 mg or 150 mg twice daily—or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism.
Results Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051).
Conclusions In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage."
This 2009 report from the New England Journal of Medicine was cited 48 times in current journal articles indexed by Thomson Reuters during January-February 2011. During that two-month period, this ranked as the fourth-most-cited medicine paper published in the last two years, aside from reviews (trumped only by three reports on the 2009 outbreak of H1N1 influenza). Prior to the most recent bimonthly count, citations to the paper have accrued as follows:
November-December 2010: 37 citations
September-October 2010: 43
July-August 2010: 41
May-June 2010: 35
March-April 2010: 35
January-February 2010: 14
November-December 2010: 17
September-October 2010: 2
