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.