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A Comparison of Two Methods of Starting the Anticoagulant Drug Warfarin
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What is the problem and what is known about it so far?
Acute venous thromboembolism is a condition in which blood clots form in veins. The clots most often occur in leg veins, causing pain and swelling. Pieces of these clots can break off and travel to the lung, a serious condition called pulmonary embolism. To treat acute venous thromboembolism, doctors prescribe anticoagulant drugs that make the blood take longer to clot. Treatment usually starts with the drug heparin, followed by treatment with warfarin. Heparin begins to work quickly but must be given by injection. Warfarin is taken by mouth, so it is easy for a patient to use at home. However, it can take several days after starting warfarin before the drug reaches a therapeutic level. A therapeutic level means that the blood is anticoagulated enough to treat the thromboembolism, but not too much. Too much warfarin can lead to bleeding complications. Doctors use a test called the international normalized ratio (INR) to see whether a person is taking the correct amount of warfarin. The correct dose varies greatly from patient to patient. The best starting dose is not clear, but many doctors start with 5 mg of warfarin. A higher starting dose might achieve a therapeutic level more quickly.
Why did the researchers do this particular study?
To see whether patients would achieve a therapeutic level of warfarin more quickly with a dosing method that starts with 10 mg of warfarin than one that starts with a 5-mg dose.
Who was studied?
201 outpatients with acute venous thromboembolism seen at one of four Canadian hospitals.
How was the study done?
The researchers assigned patients at random to begin warfarin therapy using a 5-mg starting dose strategy or a 10-mg starting dose strategy. They then saw how long it took for patients in each group to reach a therapeutic INR level. The researchers treated all patients initially with at least 5 days of a type of heparin called low-molecular-weight heparin.
What did the researchers find?
Patients in the group treated with the dosing regimen that started with 10 mg achieved a therapeutic INR 1.4 days sooner than patients in the 5-mg group. The patients in the 10-mg group also required fewer INR tests. There was no difference in bleeding complications between the two groups.
What were the limitations of the study?
This study involved only patients who were being treated as outpatients. The results may not apply to patients in the hospital. Doctors may get the same results in their outpatients only if they use exactly the same warfarin dosing strategy as the researchers used, which is more complicated than simply starting with a 10-mg initial dose.
What are the implications of the study?
Doctors should consider using the 10-mg starting dose method if they are interested in having patients achieve a therapeutic level of warfarin quickly.
Article and Author Information
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The summary below is from the full report titled “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.” It is in the 6 May 2003 issue of Annals of Internal Medicine (volume 138, pages 714-719). The authors are M.J. Kovacs, M. Rodger, D.R. Anderson, B. Morrow, G. Kells, J. Kovacs, E. Boyle, and P.S. Wells.
- Copyright ©2004 by the American College of Physicians
