Meta-analysis of trials comparing ximelagatran with low molecular weight heparin for prevention of venous thromboembolism after major orthopaedic surgery.
BACKGROUND
Use of low molecular weight heparin (LMWH) is standard practice for preventing postoperative venous thromboembolism (VTE). Ximelagatran is a new direct thrombin inhibitor for this indication.


METHODS
A systematic review was conducted to compare the efficacy and safety of LMWH with ximelagatran in orthopaedic surgery.


RESULTS
Six eligible, well conducted clinical trials (10 051 patients) were identified. Overall, the risk of VTE (OR (odds ratio) 1.22 (95 per cent confidence interval (c.i.) 0.89 to 1.67)) and serious bleeding (OR 0.70 (95 per cent c.i. 0.42 to 1.18)) was not significantly different for LMWH compared with ximelagatran. Exploratory analyses to investigate statistical heterogeneity found that results varied by surgical subtype and treatment regimen. Compared with postoperative ximelagatran, LMWH had a significantly lower rate of VTE (OR 0.68 (95 per cent c.i. 0.56 to 0.82); P < 0.001), with no significant difference in bleeding rate (OR 1.09 (95 per cent c.i. 0.62 to 1.94); P = 0.76), in hip surgery, and no significant differences in knee surgery. When ximelagatran was started immediately before surgery, LMWH had a significantly higher rate of VTE in both hip (OR 1.87 (95 per cent c.i. 1.20 to 2.92); P = 0.006) and knee (OR 1.49 (95 per cent c.i. 1.14 to 1.93); P = 0.003) surgery, but less bleeding: hip OR 0.30 (95 per cent c.i. 0.17 to 0.53; P < 0.001); knee OR 0.71 (95 per cent c.i. 0.30 to 1.67; P = 0.43).


CONCLUSIONS
This review demonstrated no overall advantage for either LMWH or ximelagatran in thromboprophylaxis following orthopaedic surgery. Benefits in VTE prevention with ximelagatran were gained at the expense of an increased risk of serious bleeding.
Cohen
A T
AT
Department of Surgery, Guy's, King's and St Thomas' Hospital School of Medicine, London, UK.
Hirst
C
C
Sherrill
B
B
Holmes
P
P
Fidan
D
D
D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use*; D019643:Arthroplasty, Replacement; D019644:Arthroplasty, Replacement, Hip; D001384:Azetidines / Q000627:therapeutic use*; D001596:Benzylamines; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D011183:Postoperative Complications / Q000517:prevention & control*; D019106:Postoperative Hemorrhage / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D013923:Thromboembolism / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000517:prevention & control*
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D006495:Heparin, Low-Molecular-Weight; C426686:ximelagatran