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

  1. Michael J. Kovacs, MD, FRCPC;
  2. Marc Rodger, MD, FRCPC, MSc;
  3. David R. Anderson, MD, FRCPC, MSc;
  4. Beverly Morrow, RN;
  5. Gertrude Kells, BScN, RN;
  6. Judy Kovacs, RN;
  7. Eleanor Boyle, BSc; and
  8. Philip S. Wells, MD, FRCPC, MSc
  1. 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.

    Abstract

    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.

    Article and Author Information

    • 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.

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    1. Ann Intern Med May 6, 2003 vol. 138 no. 9 714-719
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