Comparison of 10-mg and 5-mg warfarin initiation nomograms together with low-molecular-weight heparin for outpatient treatment of acute venous thromboembolism. A randomized, double-blind, controlled trial.
BACKGROUND
The optimal means of achieving therapeutic oral anticoagulation in the outpatient setting has not been determined.


OBJECTIVE
To compare a 10-mg dosing nomogram with a 5-mg nomogram that has been suggested to be sufficient for warfarin initiation.


METHODS
Randomized, controlled clinical trial.


METHODS
Outpatient venous thromboembolism services of four tertiary care hospitals.


METHODS
201 of 210 consecutive patients with objectively confirmed diagnoses of acute venous thromboembolism.


METHODS
All patients were treated with subcutaneous low-molecular-weight heparin for a minimum of 5 days until a therapeutic international normalized ratio (INR) was achieved. Patients were randomly assigned to initially receive a 10-mg or 5-mg dose of warfarin.


METHODS
The primary end point was time in days to therapeutic INR. Secondary end points were the proportion of patients who had achieved a therapeutic INR by day 5, the total number of INR assessments, the number of INR measurements greater than 5.0, incidence of recurrent venous thromboembolism and major bleeding, and survival.


RESULTS
210 consecutive patients met the inclusion criteria. Of these, 9 were excluded and 201 were randomly assigned to study groups (104 to the 10-mg group and 97 to the 5-mg group). Demographic characteristics of both groups were similar. Patients in the 10-mg group achieved therapeutic INR 1.4 days earlier than patients in the 5-mg group (P < 0.001). Eighty-three percent of patients in the 10-mg group achieved a therapeutic INR by day 5 versus 46% in the 5-mg group (P < 0.001). Fewer INR assessments were performed in the 10-mg group than in the 5-mg group (8.1 vs. 9.1; P = 0.04). There were no significant differences between the two groups in recurrent events, major bleeding, survival, and number of INR measurements greater than 5.0.


CONCLUSIONS
The 10-mg warfarin initiation nomogram is superior to the 5-mg nomogram because it allows more rapid achievement of a therapeutic INR.
Kovacs
Michael J
MJ
Department of Hematology, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 4G5, Canada. michael.kovacs@lhsc.on.ca
Rodger
Marc
M
Anderson
David R
DR
Morrow
Beverly
B
Kells
Gertrude
G
Kovacs
Judy
J
Boyle
Eleanor
E
Wells
Philip S
PS
D000208:Acute Disease; D000553:Ambulatory Care; D000925:Anticoagulants / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000188:drug therapy*; D020246:Venous Thrombosis / Q000188:drug therapy*; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014859:Warfarin