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

Ann Intern Med. 2003 May 6;138(9):714-9. doi: 10.7326/0003-4819-138-9-200305060-00007.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Ambulatory Care*
  • Anticoagulants / administration & dosage*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Heparin, Low-Molecular-Weight / administration & dosage*
  • Humans
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Pulmonary Embolism / drug therapy*
  • Venous Thrombosis / drug therapy*
  • Warfarin / administration & dosage*


  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Warfarin