A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome.

Abstract

BACKGROUND:

Many patients with the antiphospholipid antibody syndrome and recurrent thrombosis receive doses of warfarin adjusted to achieve an international normalized ratio (INR) of more than 3.0. However, there are no prospective data to support this approach to thromboprophylaxis.

METHODS:

We performed a randomized, double-blind trial in which patients with antiphospholipid antibodies and previous thrombosis were assigned to receive enough warfarin to achieve an INR of 2.0 to 3.0 (moderate intensity) or 3.1 to 4.0 (high intensity). Our objective was to show that high-intensity warfarin was more effective in preventing thrombosis than moderate-intensity warfarin.

RESULTS:

A total of 114 patients were enrolled in the study and followed for a mean of 2.7 years. Recurrent thrombosis occurred in 6 of 56 patients (10.7 percent) assigned to receive high-intensity warfarin and in 2 of 58 patients (3.4 percent) assigned to receive moderate-intensity warfarin (hazard ratio for the high-intensity group, 3.1; 95 percent confidence interval, 0.6 to 15.0). Major bleeding occurred in three patients assigned to receive high-intensity warfarin and four patients assigned to receive moderate-intensity warfarin (hazard ratio, 1.0; 95 percent confidence interval, 0.2 to 4.8).

CONCLUSIONS:

High-intensity warfarin was not superior to moderate-intensity warfarin for thromboprophylaxis in patients with antiphospholipid antibodies and previous thrombosis. The low rate of recurrent thrombosis among patients in whom the target INR was 2.0 to 3.0 suggests that moderate-intensity warfarin is appropriate for patients with the antiphospholipid antibody syndrome.

• Authors: Mark A Crowther, Jeff S Ginsberg, Jim Julian, Judah Denburg, Jack Hirsh, James Douketis, Carl Laskin, Paul Fortin, David Anderson, Clive Kearon, Ann Clarke, William Geerts, Melissa Forgie, David Green, Lorrie Costantini, Wendy Yacura, Sarah Wilson, Michael Gent, Michael J Kovacs
• Journal: The New England journal of medicine (N Engl J Med) Vol. 349 Issue 12 Pg. 1133-8 (Sep 18 2003) ISSN: 1533-4406 [Electronic] United States
• PMID: 13679527 (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

• Antibodies, Antiphospholipid
• Anticoagulants
• Warfarin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Antiphospholipid (blood)
• Anticoagulants (administration & dosage, adverse effects)
• Antiphospholipid Syndrome (blood, complications, drug therapy)
• Double-Blind Method
• Female
• Follow-Up Studies
• Hemorrhage (chemically induced)
• Humans
• International Normalized Ratio
• Male
• Middle Aged
• Myocardial Infarction (prevention & control)
• Pulmonary Embolism (prevention & control)
• Secondary Prevention
• Stroke
• Venous Thrombosis (prevention & control)
• Warfarin (administration & dosage, adverse effects)