Prevention of venous thromboembolic disease following primary total knee arthroplasty - A randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin

Background: Patients treated with total knee arthroplasty are at high risk for the development of venous thrombo-embolism postoperatively. This study compared the efficacy and safety of two common thromboprophylactic agents, enoxaparin (a low-molecular-weight heparin) and warfarin. Methods: Three hundred and forty-nine patients were included in a prospecti ve, randomized, multicenter, open-label, parallel-group clinical trial. Tre atment with enoxaparin (30 mg, administered subcutaneously twice daily) or warfarin (adjusted to an international normalized ratio of 2 to 3) was init iated during the immediate postoperative period, within eight hours after t he surgery, and was continued for four to fourteen days. Venous thromboembo lism was defined as deep-vein thrombosis documented by contrast venography, symptomatic deep-vein thrombosis documented by lower-extremity ultrasonogr aphy, or symptomatic pulmonary embolism confirmed by a positive lung scan o r pulmonary angiography. Results: In the all-treated-patients group, eighty (45%) of the 176 warfari n-treated patients had venous thromboembolism: fifty-nine (34%) had distal deep-vein thrombosis; twenty (11%), proximal deep-vein thrombosis; and one (0.6%), pulmonary embolism. Venous thromboembolism developed in significant ly fewer (p = 0.0001) enox- aparin-treated patients (forty-four of 173; 25% ): forty-one (24%) had distal deep-vein thrombosis, three (2%) had proximal deep-vein thrombosis, and none had pulmonary embolism. The enoxaparin-trea ted patients also had a significantly lower prevalence of proximal deep-vei n thrombosis (p = 0.002). The estimated odds for the development of venous thromboembolism were 2.52 times greater (95% confidence interval, 2.00 to 3 .19) with warfarin than they were with enoxaparin. Major hemorrhage occurre d in four warfarin-treated patients and nine enoxaparin-treated patients; w ith the numbers available, this difference was not significant (p = 0.17). clinically important operative-site hemorrhage occurred in six (3%) of the warfarin-treated patients and twelve (7%) of the enoxaparin-treated patient s (p = 0.15). Conclusions: A fixed 30-mg subcutaneous dose of enoxaparin, administered tw ice daily, with the first dose administered within eight hours after the co mpletion of surgery, was significantly more effective than adjusted-dose wa rfarin in reducing the occurrence of asymptomatic venous thromboembolism, i ncluding proximal deep-vein thrombosis, in patients undergoing total knee a rthroplasty. With the numbers available, there was no significant differenc e between groups with regard to the occurrence of major hemorrhagic complic ations; however, the rate of overall hemorrhagic complications was higher i n the enoxaparin group.