Low-dose warfarin in rehabilitating stroke survivors.
BACKGROUND
Patients undergoing rehabilitation after thromboembolic stroke have a relatively high incidence of venous thromboembolism (VTE). Warfarin, with a target international normalized ratio (INR) of 2.0-3.0 is effective for the prevention of VTE. However, because stroke is a major risk factor for bleeding with warfarin, a less intense regimen (target INR < 2.0), might safely prevent VTE in stroke rehabilitation patients.


METHODS
This study was a randomized, double-blind, placebo-controlled trial of 2 mg of warfarin in patients undergoing rehabilitation following completed stroke. The major efficacy endpoint was symptomatic, objectively proven VTE or asymptomatic VTE detected by monthly duplex ultrasonography (DU) of the proximal leg veins or mandatory bilateral contrast venography performed at the end of the study. The major safety endpoint was bleeding.


RESULTS
There were 475 patients screened for enrollment, 355 had one or more exclusion criterion, and 17 had previously undetected proximal DVT on admission. Of the 103 eligible and consenting patients, 56 received warfarin and 47 received placebo. Of the randomized patients, 88 had successful venography (47 warfarin and 41 placebo). In the warfarin group, three (8%) patients had DVT and one (2%) had proximal DVT whereas in the placebo group, seven (20%) had DVT and five (13%) had proximal DVT. The risk ratio for any DVT in warfarin-treated patients relative to placebo-treated patients was 0.39 (95% confidence interval (CI), 0.13-1.37). For proximal DVT, the risk ratio was 0.17 (95% CI, 0.01-1.4). No patients suffered major bleeding.


CONCLUSIONS
A fixed dose of 2 mg of warfarin per day in patients undergoing stroke rehabilitation is safe and associated with a relative risk reduction of about 80% in the incidence of proximal DVT and 60% in overall DVT.
Ginsberg
Jeffrey S
JS
Department of Medicine, McMaster University Medical Centre, 1200 Main Street West Rm 3X28, Hamilton, Ontario L8N 3Z5, Canada. ginsbrgj@mcmaster.ca
Bates
Shannon M
SM
Oczkowski
Wieslaw
W
Booker
Nicola
N
Magier
Deb
D
MacKinnon
Betsy
B
Weitz
Jeffrey
J
Kearon
Clive
C
Cruickshank
Moira
M
Julian
Jim A
JA
Gent
Michael
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010690:Phlebography; D000071939:Stroke Rehabilitation; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000175:diagnosis / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D014859:Warfarin