Dabigatran versus warfarin in patients with atrial fibrillation.
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. (ClinicalTrials.gov number, NCT00262600.)
Connolly
Stuart J
SJ
Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada. connostu@phri.ca
Ezekowitz
Michael D
MD
Yusuf
Salim
S
Eikelboom
John
J
Oldgren
Jonas
J
Parekh
Amit
A
Pogue
Janice
J
Reilly
Paul A
PA
Themeles
Ellison
E
Varrone
Jeanne
J
Wang
Susan
S
Alings
Marco
M
Xavier
Denis
D
Zhu
Jun
J
Diaz
Rafael
R
Lewis
Basil S
BS
Darius
Harald
H
Diener
Hans-Christoph
HC
Joyner
Campbell D
CD
Wallentin
Lars
L
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D016009:Chi-Square Distribution; D000069604:Dabigatran; D004311:Double-Blind Method; D004415:Dyspepsia / Q000139:chemically induced; D004617:Embolism / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D011355:Prodrugs / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000925:Anticoagulants; D001562:Benzimidazoles; D011355:Prodrugs; D011725:Pyridines; D014859:Warfarin; D000069604:Dabigatran