Abstract 6048: An Indirect Comparison of the Efficacy and Safety of Factor Xa Inhibitors with Thrombin Inhibitors nn Preventing Venous Thromboembolism after Hip or Knee Surgery
Introduction Selective factor Xa inhibitors and thrombin inhibitors are effective in the prevention of venous thromboembolism (VTE) after hip or knee surgery, but they have not been compared directly against each other. We performed an indirect comparison of the relative efficacy and safety of these two classes of inhibitors, from meta-analyses of randomized controlled trials (RCTs) of these agents, in which a low molecular heparin (LMWH) was used as a common comparator.
Methods Relevant RCTs were identified by searching MEDLINE (Ovid MEDLINE® 1950 to March week 1, 2008), EMBASE (1980 to 2008, week 10) and the Cochrane Central Register of Controlled Trials (1st quarter 2008), supplemented by hand searching and screening meeting websites. We restricted our search to the five agents (ximelagatran, dabigatran, fondaparinux, idraparinux and rivaroxaban) that have been evaluated in phase III trials. Trials were included if the study drug was compared against a LMWH and was administered in the pre- and/or postoperative (12–24hrs from surgery) period, to patients undergoing elective, hip or knee replacement surgery. The outcomes assessed were total VTE, symptomatic VTE, major bleeding and the need for blood transfusions. We obtained summary estimates (RR and 95% CI) for each outcome for the Xa and thrombin inhibitor studies, using a random-effects model. We then performed indirect comparisons between these estimates using standard statistical methods.
Results We included 12 trials (18110 patients) of factor Xa inhibitors (fondaparinux, rivaroxaban) and 10 trials (17777 patients) of thrombin inhibitors (ximelagatran, dabigatran). These agents were compared with enoxaparin, except in two studies where dalteparin was the control agent. On indirect comparison, factor Xa inhibitors were significantly better than thrombin inhibitors in preventing total VTE (RR 0.54, 95% CI 0.40 – 0.75) and symptomatic VTE (RR 0.49, 95% CI 0.25– 0.97). There was no difference in the risk of major bleeding (RR 1.17, 95% CI 0.71–1.93) or the number of transfusions (RR 1.02, 95% CI 0.94–1.11).
Conclusion Based on this indirect comparison, selective factor Xa inhibitors appear to be more effective than thrombin inhibitors, for the prevention of VTE after elective hip or knee surgery.