Summary

The oral direct thrombin inhibitor ximelagatran (24 mg twicedaily) has been shown to significantly reduce the incidence of recurrentvenous thromboembolism (VTE) vs. placebo over 18months, with no significant influence on bleeding (THRIVE III).The influence of potential prognostic factors on the risk of recurrentVTE or major and/or minor bleeding and their impacton ximelagatran treatment was evaluated in theTHRIVE III studypopulation. The effect of sex, age, body weight, renal function,malignancy, type of initialVTE event, and history of previousVTEevents was investigated in the intention-to-treat populationusing Cox proportionate hazard modelling. Ximelagatran wasadministered to 612 patients and placebo to 611 patients.Withinthe placebo group, risk of recurrent VTE was higher amongmen than women (hazard ratio [HR]: 2.50,95% confidence interval [CI] 1.49, 4.17), and in patients with one or more than oneprevious VTE event (HR: 1.73, 95% CI 1.00, 2.99). There was ahigher risk of bleeding among women than men in both theximelagatran (HR: 1.49, 95% CI 1.06, 2.09) and placebo (HR:1.48, 95% CI 1.01, 2.15) groups, and in placebo-treated patientswith an initial pulmonary embolism (HR: 1.53, 95% CI 1.06, 2.23)compared to those with initial deep vein thrombosis. Therewere no significant interactions between treatment effect andany of the potential prognostic factors. In conclusion, the superiorefficacy of ximelagatran vs. placebo was maintained in allsubgroups. Long-term use of oral ximelagatran, without coagulationmonitoring or dose adjustment, should be feasible andwell tolerated in a wide cross-section of patients for the secondaryprevention of V