To produce an adequate anticoagulant effect, warfarin therapy must be monitored carefully, with the dosage adjusted to maintain the prothrombin time (PT) in a safe and effective range, usually equivalent to an International Normalized Ratio (INR) of 2.0 to 3.0. Intensive monitoring of the patient's response during the initiation of warfarin therapy lasts a minimum of four to five days and is no longer required when the INR has remained in the therapeutic range for two consecutive days. A previous study by Crowther and associates suggested that a starting dose of 5 mg is as effective in producing an anticoagulant effect by the fourth or fifth day as a dose of 10 mg. To further investigate this observation, the authors prospectively studied the anticoagulant effects of 5-mg and 10-mg loading doses of warfarin to determine if the number of days required to achieve a therapeutic INR differed with these two starting doses.
The study consisted of 53 patients (28 women) who required anticoagulant therapy; 32 patients were randomly assigned to receive an initial warfarin dose of 5 mg, and 21 were assigned to receive an initial dose of 10 mg. The goal of therapy was a target INR of 2.0 to 3.0. The INR was measured daily for five days. The primary end point was therapeutic INR values on two consecutive days by the fourth or fifth day of therapy.
INR values of 2.0 to 3.0 were consistently more common at all time points in patients who received the 5-mg dose than in patients who received the 10-mg dose. The primary end point was achieved in five of the 21 patients (24 percent) in the 10-mg group, compared with 21 of the 32 patients (66 percent) in the 5-mg group. INR values on the fourth day were greater than 3.0 in five of the 21 patients (24 percent) who received a loading dose of 10 mg. In contrast, they were above 3.0 in two of 30 patients (7 percent) who received the 5-mg loading dose.
The authors conclude that an initial warfarin dose of 5 mg does not delay the attainment of an INR of 2.0 to 3.0 on day 3, 4 or 5 of therapy. The present study corroborates the authors' previous observation that a 5-mg starting dose of warfarin is as effective as a 10-mg loading dose.