Thirteen RCTs were included for review (n=22, 639). There was some evidence of publication bias for major adverse events but not for major bleeds or hepatic toxicity.
Major bleeds: When all studies were combined, there was no significant difference between ximelagatran/melagatran and conventional anticoagulant therapy in the rate of major bleeds, but there was evidence of significant heterogeneity for these outcomes. Ximelagatran/melagatran was associated with significantly lower risk of major bleeds in the treatment of deep vein thrombosis (OR 0.51, 95% CI: 0.27 to 0.98; two RCTs) and in the prevention of atrial fibrillation-related stroke (OR 0.71, 95% CI: 0.55 to 0.92; three RCTs) compared to conventional anticoagulant therapy.
Major adverse events: Ximelagatran/melagatran was not associated with any significant difference in the risk of major adverse events compared to conventional anticoagulant therapy. There was no evidence of significant statistical heterogeneity for these outcomes.
Hepatic toxicity: When all studies were combined, ximelagatran/melagatran was not associated with a significantly increased risk of hepatic toxicity, but there was evidence of significant statistical heterogeneity. When used in the treatment of deep vein thrombosis (OR 5.16, 95% CI: 3.38 to 7.89; two RCTs) and in the prevention of atrial fibrillation-related stroke (OR 8.31, 95% CI: 5.65 to 12.23; three RCTs), ximelagatran/melagatran was associated with a significantly increased risk of hepatic toxicity. Use of ximelagatran/melagatran for three months or more was associated with a significantly increased risk of hepatic toxicity (OR 6.73, 95% CI: 5.01 to 9.05). There was no evidence of significant statistical heterogeneity for these outcomes.
Sensitivity analyses did not significantly alter the results.