Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism.

Abstract

BACKGROUND:

Warfarin is very effective in preventing recurrent venous thromboembolism but is also associated with a substantial risk of bleeding. After three months of conventional warfarin therapy, a lower dose of anticoagulant medication may result in less bleeding and still prevent recurrent venous thromboembolism.

METHODS:

We conducted a randomized, double-blind study, in which 738 patients who had completed three or more months of warfarin therapy for unprovoked venous thromboembolism were randomly assigned to continue warfarin therapy with a target international normalized ratio (INR) of 2.0 to 3.0 (conventional intensity) or a target INR of 1.5 to 1.9 (low intensity). Patients were followed for an average of 2.4 years.

RESULTS:

Of 369 patients assigned to low-intensity therapy, 16 had recurrent venous thromboembolism (1.9 per 100 person-years), as compared with 6 of 369 assigned to conventional-intensity therapy (0.7 per 100 person-years; hazard ratio, 2.8; 95 percent confidence interval, 1.1 to 7.0). A major bleeding episode occurred in nine patients assigned to low-intensity therapy (1.1 events per 100 person-years) and eight patients assigned to conventional-intensity therapy (0.9 event per 100 person-years; hazard ratio, 1.2; 95 percent confidence interval, 0.4 to 3.0). There was no significant difference in the frequency of overall bleeding between the two groups (hazard ratio, 1.3; 95 percent confidence interval, 0.8 to 2.1).

CONCLUSIONS:

Conventional-intensity warfarin therapy is more effective than low-intensity warfarin therapy for the long-term prevention of recurrent venous thromboembolism. The low-intensity warfarin regimen does not reduce the risk of clinically important bleeding.

• Authors: Clive Kearon, Jeffrey S Ginsberg, Michael J Kovacs, David R Anderson, Philip Wells, Jim A Julian, Betsy MacKinnon, Jeffrey I Weitz, Mark A Crowther, Sean Dolan, Alexander G Turpie, William Geerts, Susan Solymoss, Paul van Nguyen, Christine Demers, Susan R Kahn, Jeannine Kassis, Marc Rodger, Julie Hambleton, Michael Gent, Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 349 Issue 7 Pg. 631-9 (Aug 14 2003) ISSN: 1533-4406 [Electronic] United States
• PMID: 12917299 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2003 Massachusetts Medical Society

Chemical References

• Anticoagulants
• Warfarin

Topics

• Age Factors
• Aged
• Anticoagulants (administration & dosage, adverse effects)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Hemorrhage (chemically induced)
• Humans
• International Normalized Ratio
• Male
• Middle Aged
• Pulmonary Embolism (mortality, prevention & control)
• Risk Factors
• Secondary Prevention
• Treatment Outcome
• Venous Thrombosis (prevention & control)
• Warfarin (administration & dosage, adverse effects)