A randomized trial comparing 5-mg and 10-mg warfarin loading doses

Background: Warfarin sodium therapy is usually initiated with a loading dos e to reduce the time required to elevate the international normalized ratio (INR). Warfarin loading doses are associated with early overanticoagulatio n and the development of a potential hypercoagulable state; they also may n ot hasten achieving an INR value between 2.0 and 3.0. This study was design ed to prospectively confirm our observation that a 5-mg warfarin sodium loa ding dose is as effective as a 10-mg loading dose in achieving a therapeuti c INR for 2 consecutive days on days 3 and 4 or 4 and 5 of therapy. Me)hods: Fifty-three patients initiating warfarin therapy with a target INR of 2.0 to 3.0 were randomly allocated to receive an initial dose of 5 or 1 0 mg of warfarin. Subsequent doses were based on dosing algorithms. The INR was measured daily for 5 days. The primary end point of the study was the proportion of patients whose INR values were between 2.0 and 3.0 on 2 conse cutive daily determinations on days 3, 4, or 5 of the study and whose INR d id not exceed 3.0 at any point during the study. Results: Five (24%) of 21 patients in the 10-mg group and 21 (66%) of 32 pa tients in the 5-mg group achieved the primary end point (relative risk 2.22 , 95% confidence interval 1.30-3.70 [P < .003]). A trend toward less overan ticoagulation was seen in the 5-mg warfarin group. Conclusion: A 10-mg loading dose of warfarin is unlikely to be more effecti ve than a 5-mg loading dose in achieving an INR of 2.0 to 3.0 by day 4 or 5 of therapy.