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ARTICLE

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

Michael J. Kovacs, MD, FRCPC; Marc Rodger, MD, FRCPC, MSc; David R. Anderson, MD, FRCPC, MSc; Beverly Morrow, RN; Gertrude Kells, BScN, RN; Judy Kovacs, RN; Eleanor Boyle, BSc; and Philip S. Wells, MD, FRCPC, MSc

6 May 2003 | Volume 138 Issue 9 | Pages 714-719

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.

Editors' Notes Context The optimal methods for achieving therapeutic levels of anticoagulation with warfarin remain uncertain. Contribution In this randomized trial of two warfarin dosing nomograms, a 10-mg initiation dose led to a therapeutic international normalized ratio (INR) 1.4 days sooner than a 5-mg initiation dose. The two nomograms had the same rate of adverse events and the same proportion of INR values greater than 5.0. Clinical Implications Physicians can more quickly get their patients to a therapeutic INR with warfarin by using a dosing nomogram that starts with a 10-mg dose rather than a 5-mg initiation dose. –The Editors

 

Author and Article 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.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Michael J. Kovacs, MD, FRCPC, Department of Hematology, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 4G5, Canada; e-mail, michael.kovacs{at}lhsc.on.ca.

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 Hospital—Civic 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 http://rctbank.ucsf.edu/Presenter?518. Annals does not maintain the trials bank.

Related articles in Annals:

Summaries for Patients
A Comparison of Two Methods of Starting the Anticoagulant Drug Warfarin

Annals 2003 138: I-50. [Full Text]  

Letters
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