Comparison of a Nomogramand Physician-Adjusted Dosageof Warfarin for Prophylaxis Against Deep-Vein Thrombosis After Arthroplasty

Background: Warfarin is an effective agent for prophylaxis against deep-vein thrombosis following total hip or knee arthroplasty. However, management with warfarin in the postoperative setting is problematic because of the need for anticoagulant monitoring. We developed a nomogram for the dosing of warfarin that was specific for joint arthroplasty. The objective of this study was to compare the performance of this nomogram with that of physician-adjusted dosing of warfarin for patients undergoing total hip or knee arthroplasty.

Methods: The study involved two cohort trials. The historical control group consisted of 1024 patients who underwent total hip or knee arthroplasty during the course of a clinical trial (the Post-Arthroplasty Screening Study [PASS]) in which all warfarin dose adjustments were made by two hematologists. The first dose of warfarin was given on the evening of the surgery, and the warfarin dose was adjusted daily on the basis of the international normalized ratio and was discontinued at the time of discharge from the hospital. In the PASS study, the dosage of warfarin was designed to prolong the international normalized ratio to 1.7 by postoperative day 4 and to maintain it between 1.8 and 2.5 until discharge from the hospital. Subsequently, a warfarin nomogram was developed on the basis of the dose adjustments used in the PASS study, and it was used prospectively to manage a cohort of 729 patients undergoing total hip or knee arthroplasty. In the nomogram cohort, the initial dose of warfarin was given on the evening of the surgery. Both cohorts were followed for twelve weeks after the surgery to determine if any venous thromboembolic complications had developed.

Results: The nomogram cohort and the control cohort had similar daily doses of warfarin (mean, 3.2 versus 3.3 mg) and levels of international normalized ratio on postoperative day 4 (mean, 1.9 versus 1.9) (p > 0.2). The average number of days to achieve an international normalized ratio of >1.7 was 4.0 for the nomogram cohort compared with 4.3 for the control cohort (p = 0.01). The percentage of days that the international normalized ratio was between 1.8 and 2.5 was 61% for the nomogram cohort and 58% for the control cohort (p < 0.01), and the percentage of days that the international normalized ratio was >3.0 was only 6.5% for the nomogram cohort and 6.0% for the control cohort (p > 0.2). Eighty-two percent of the patients managed with the nomogram achieved an international normalized ratio of >1.7 by the time of discharge from the hospital compared with 92% in the control cohort (p = 0.01). In the three-month follow-up period, a deep-vein thrombosis or a nonfatal pulmonary embolism developed in nineteen patients (2.6%; 95% confidence interval, 1.6% to 4.0%) in the nomogram cohort compared with fourteen patients (1.4%; 95% confidence interval, 0.7% to 2.3%) in the control cohort. No major bleeding event or fatal pulmonary embolism was observed in the patients managed with use of the nomogram.

Conclusion: This study demonstrated that the administration of warfarin during hospitalization with use of a nomogram designed for the prevention of deep-vein thrombosis following total hip or knee arthroplasty provided effective and safe prophylaxis that was comparable with that provided by physician-adjusted dosing of warfarin.