Background: The safety and efficacy of new anticoagulants are often initially tested for venous thromboembolism (VTE) prevention in patients undergoing major orthopedic surgery. Concern among surgeons about the risks for bleeding may result in suboptimal use of thrombophylaxis.
Objective: To evaluate the definitions used to define bleeding outcomes in studies of new anticoagulants and to examine the influence the definition has on the perceived bleeding risk of thromboprophylaxis.
Methods: The MedLine database was searched for phase III studies of new anticoagulants versus the standard comparator, enoxaparin, in patients undergoing major orthopedic surgery.
Results: The definitions for major bleeding outcomes varied widely both across and within clinical trial programs of new anticoagulants. Studies which did not include surgical site bleeding in their definition for major bleeding showed lower major bleeding rates in comparison to those that did include this outcome. Other factors that influenced the rate of major bleeding included the timing of prophylaxis initiation in relation to surgery and the dose of anticoagulant therapy. The wide range of definitions used for major bleeding made it difficult to compare bleeding risk among studies of new anticoagulants.
Conclusions: The definitions of bleeding events that clinical trials of thromboprophylaxis use in their assessment of new anticoagulants strongly influences each drug's perceived safety profile and may underestimate bleeding risks. Clinical studies of new anticoagulants urgently need standardization of bleeding definitions to allow intertrial comparability and to ensure consistent reporting of clinically relevant outcomes.