Safety and efficacy of ximelagatran: meta-analysis of the controlled randomized trials for the prophylaxis or treatment of venous thromboembolism.

BACKGROUND: Ximelagatran has been approved in Europe for VTE prophylaxis in orthopedic surgery at fixed doses and without laboratory monitoring. Aim of the study was to evaluate safety and efficacy of ximelagatran in a meta-analysis of prophylaxis and/or treatment randomized controlled trials. METHODS: Absolute risk of events for ximelagatran and OR for its comparison with LMWH and coumarins were calculated. Subgroup analysis was performed for ximelagatran regimen, comparator agent, type of surgery, starting time of prophylaxis. RESULTS: Twelve studies and 16,992 patients were meta-analysed. Ximelagatran showed an absolute risk of major VTE of 4.04% and 1.69% and of major bleedings of 1.68% and 1.03% in prophylaxis and treatment trials, respectively. In prophylaxis trials, a significant excess mortality (OR: 2.5; 95% CI: 1.02 - 6.13) and an excess in major bleedings (OR: 1.41; 95% CI: 0.93 - 2.14) was found in the whole ximelagatran group. No evidence of treatment effect for major VTE was seen in the comparison with LMWH (OR: 1.01; 95% CI: 0.52 - 1.97). The cohort of patients treated with 24 mg b.i.d. showed similar results. An increase in the absolute risk of bleeding (from 1.04% to 3.03%) was found between post and preoperative administration of ximelagatran. Major VTE risk was increased when ximelagatran was compared to b.i.d. LMWH. CONCLUSIONS: Ximelagatran can be considered for its potential advantages for prevention and treatment of VTE. Future efforts are needed by researchers to prospectively investigate the best postoperatively starting time and by clinicians to monitor overall mortality in prophylactic use.