Bleeding profiles of anticoagulants, including the novel oral direct thrombin inhibitor ximelagatran: definitions, incidence and management

Ximelagatran is a novel oral direct thrombin inhibitor (oral DTI) that is currently in advanced clinical development for the prevention and treatment of thromboembolic events in a wide range of patient populations and indications. The clinical development of novel anticoagulant therapies requires that treatments be assessed according to both their clinical benefit (reduction of risk of thromboembolic events) and safety profile (primarily bleeding). Definition and assessment of bleeding severity is thus an important factor in clinical trial design. Lack of consistency in bleeding definitions used in different clinical trial programmes makes comparison of bleeding event data difficult. Standard bleeding definitions would be required to make fair comparisons between clinical trials possible. The definitions of bleeding events used in clinical trials of ximelagatran are broadly consistent with those used in many other major trials. Results of phase II and III trials comparing ximelagatran with currently available anticoagulant therapies demonstrate that ximelagatran can be used with fixed dosing with no coagulation monitoring, dose titration, or dose adjustment, without compromising efficacy or safety. The incidences of major bleeding events in clinical trials of ximelagatran have been low and similar to those with other anticoagulant drugs. Adequate treatment in case of emergency situations such as serious bleeding should include cessation of treatment and maintenance of adequate diuresis.