Fondaparinux prevents venous thromboembolism after joint replacement surgery in Japanese patients.
Venous thromboembolism (VTE) is an important complication of major orthopaedic surgery of the lower limbs. Fondaparinux, a synthetic pentasaccharide and highly selective inhibitor of activated Factor Xa, is the first in a new class of antithrombotic agents. To determine the optimal dose in Japanese patients, double-blind, placebo-controlled, dose-ranging studies of fondaparinux were conducted in patients undergoing total knee replacement (TKR) or total hip replacement (THR) surgery. Patients were randomly assigned to receive a once-daily subcutaneous injection of fondaparinux (0.75, 1.5, 2.5, or 3.0 mg) or placebo in Study 1 (TKR) and Study 2 (THR). In Study 1, the incidence of VTE was 65.3% in the placebo group and was 34.2%, 21.3%, 16.2%, and 9.5% in the groups receiving 0.75, 1.5, 2.5, and 3.0 mg fondaparinux respectively. In Study 2, the incidence of VTE was 33.8% in the placebo group and was 24.2%, 4.6%, 7.4%, and 14.4% in the 0.75, 1.5, 2.5, and 3.0 mg fondaparinux groups respectively. Dose-response effects were observed in both studies; however, no statistically significant differences in major bleeding events were found among any groups. Fondaparinux proved to be a potent anticoagulant with a favourable benefit-to-risk ratio in the prevention of VTE in these study patients.
Fuji
Takeshi
T
Department of Orthopaedic Surgery, Osaka Koseinenkin Hospital, 4-2-78 Fukushima, Fukushima-ku, Osaka 553-0003, Japan. fuji-th@umin.ac.jp
Fujita
Satoru
S
Ochi
Takahiro
T
D000368:Aged; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D000077425:Fondaparinux; D006801:Humans; D007564:Japan; D008297:Male; D010919:Placebos; D011134:Polysaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000209:etiology / Q000517:prevention & control*
D010919:Placebos; D011134:Polysaccharides; D000077425:Fondaparinux