Prevention of postoperative venous thromboembolism in Japanese patients undergoing total hip or knee arthroplasty: two randomized, double-blind, placebo-controlled studies with three dosage regimens of enoxaparin

Background. Enoxaparin is a low-molecular-weight heparin indicated in Europe and North America for the prevention of venous thromboembolism (VTE) in patients undergoing major orthopedic surgery. Registration trials of enoxaparin have been conducted primarily in Caucasian populations, and the efficacy and safety of enoxaparin in Japanese patients have not been demonstrated. We evaluated three dosage regimens of postoperative enoxaparin in Japanese patients undergoing elective total hip or knee arthroplasty. Methods. Two multicenter, randomized, double-blind studies enrolled 436 and 396 Japanese adults undergoing total hip or knee arthroplasty, respectively. The dosage regimens of enoxaparin were 20 mg once daily (qd), 40 mg qd, 20 mg twice daily (bid), or placebo for 14 consecutive days. The primary efficacy endpoint was the incidence of VTE in the modified intention-to-treat (mITT) population up to 15 days after surgery. VTE was defined as a composite of deep vein thrombosis (determined by venography) and symptomatic pulmonary embolism (confirmed by appropriate objective methods). Patients were also followed up at 90 days for VTE events. The primary safety outcome was the incidence of any bleeding during treatment and the follow-up period. Results. In the mITT populations, the incidence of VTE was 41.9% and 60.8% in the placebo groups after hip or knee arthroplasty, respectively, 25.9% and 44.9% in the enoxaparin 20 mg qd groups, 33.8% and 35.1% in the enoxaparin 40 mg qd groups, and 20.0% and 29.8% in the enoxaparin 20 mg bid groups. Only enoxaparin 20 mg bid significantly lowered the risk of VTE relative to placebo (by 52.2% and 51.0% after hip and knee arthroplasty, respectively). At the 90-day follow-up, no further cases of VTE were reported. In both the hip and knee studies, the four treatment groups did not differ significantly regarding the incidence of patients with any bleeding. Conclusions. Our findings support the use of enoxaparin (20 mg bid daily, commencing 24-36 h postoperatively) in Japanese patients undergoing total hip or knee arthroplasty.