Reply: Warfarin: Less May Be Better

IN RESPONSE:

To address the questions raised by Dr. Adelman and others, the dose-adjustment algorithms used in our study are presented in the (Figure 1). Patients received 5 mg or 10 mg of warfarin on day 1 and day 2; the day 2 dose was reduced only if an excess anticoagulant effect was seen on the INR determination performed 12 to 16 hours after the first warfarin dose was given. The third and subsequent warfarin doses were based on the INR response and were adjusted according to the appropriate algorithm. The mean warfarin doses administered in the 5-mg group were 5.0 mg, 4.7 mg (95% CI, 4.2 to 5.2 mg), 5.8 mg (CI, 4.9 to 6.8 mg), 5.2 mg (CI, 3.9 to 6.6 mg), 3.5 mg (CI, 2.6 to 4.5 mg), and 3.7 mg (CI, 2.0 to 5.3 mg). In the 10-mg group, the mean doses were 10.0 mg, 9.7 mg (CI, 9.3 to 10.1 mg), 4.9 mg (CI, 3.3 to 6.5 mg), 3.5 mg (CI, 1.8 to 5.2 mg), 4.0 mg (CI. 2.7 to 5.3 mg) and 4.5 mg (CI, 2.9 to 6.0 mg).

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Figure 1. Dosing nomograms for 5-mg and 10-mg warfarin doses.

In response to Dr. Atkins' question, the average age of the patients was 64.8 years (66.2 years in the 5-mg group and 63.4 years in the 5-mg group). Twenty-one of 24 patients in the 5-mg group and 18 of 25 patients in the 10-mg group were receiving warfarin for acute venous thromboembolism. Five of the episodes of thromboembolism in the 5-mg group and nine of the episodes in the 10-mg group occurred after a surgical procedure that required hospital admission. Eight patients in the 5-mg group (all of whom were receiving warfarin for acute thromboembolism) were known to have an active condition, as were 4 patients in the 10-mg group (3 of whom had acute thromboembolism). Most patients in both groups were inpatients.

We acknowledge that many physicians would not administer vitamin K for INRs less than 6.0, but there is clear evidence that the risk for hemorrhage increases in proportion to the INR [1]. In addition, low-dose subcutaneous or oral vitamin K [2] is not associated with warfarin resistance and carries little or no risk for other complications. We therefore often administer 1 mg of oral vitamin K to patients with INRs greater than 4.5. The INRs for which vitamin K was administered in our study were 4.6, 4.8, 5.2, 6.0, and 9.3. Dr. Casner also questions the loss of seven patients in both groups after 108 hours of the study: One patient in the 10-mg group was lost to follow-up after the 60-hour INR was measured; the other 48 patients were followed for 84 hours. Thirteen patients did not have INRs measured at 108 hours because they had had INRs of 2.0 to 3.0 on the previous two determinations.

We agree with the comments of Drs. Carnahan and Bracikowski.

• Copyright ©2004 by the American College of Physicians