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.
Design:
Randomized, controlled clinical trial.
Setting:
Outpatient venous thromboembolism services of four tertiary care hospitals.
Patients:
201 of 210 consecutive patients with objectively confirmed diagnoses of acute venous thromboembolism.
Intervention:
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.
Measurements:
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.
Conclusion:
The 10-mg warfarin initiation nomogram is superior to the 5-mg nomogram because it allows more rapid achievement of a therapeutic INR.
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Author, Article, and Disclosure Information
From London Health Science Centre, London, and Ottawa Health Research Institute, Ottawa, Ontario, Canada; and Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
Disclosures: None disclosed.
Corresponding Author: Michael J. Kovacs, MD, FRCPC, Department of Hematology, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 4G5, Canada; e-mail, michael.
Current Author Addresses: Dr. Kovacs, Ms. Morrow, Ms. Kovacs, and Ms. Boyle: Department of Hematology, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 4G5, Canada.
Drs. Rodger and Wells: Ottawa HospitalCivic Campus, 1053 Carling Avenue, Ottawa, Ontario K1Y 4E9, Canada.
Dr. Anderson and Ms. Kells: Queen Elizabeth II Health Sciences Centre, 1278 Tower Road, Halifax, Nova Scotia B3H 2Y9, Canada.
Author Contributions: Conception and design: M.J. Kovacs, M. Rodger, D.R. Anderson, E. Boyle, P.S. Wells.
Analysis and interpretation of the data: M.J. Kovacs, M. Rodger, D.R. Anderson, P.S. Wells.
Drafting of the article: M.J. Kovacs, M. Rodger, P.S. Wells.
Critical revision of the article for important intellectual content: M.J. Kovacs, M. Rodger, D.R. Anderson, P.S. Wells.
Final approval of the article: M.J. Kovacs, M. Rodger, D.R. Anderson, B. Morrow, J. Kovacs, E. Boyle, P.S. Wells.
Provision of study materials or patients: M.J. Kovacs, M. Rodger, D.R. Anderson, G. Kells, P.S. Wells.
Statistical expertise: M. Rodger, E. Boyle, P.S. Wells.
Obtaining of funding: M. Rodger.
Administrative, technical, or logistic support: M.J. Kovacs, M. Rodger, D.R. Anderson, P.S. Wells.
Collection and assembly of data: M.J. Kovacs, M. Rodger, D.R. Anderson, B. Morrow, G. Kells, J. Kovacs, P.S. Wells.
A detailed description of the study methodology and patient flow is available in a trials bank at rctbank.ucsf.edu/Presenter?518. Annals does not maintain the trials bank.
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