Abstract 14413: Evaluation of the Acute Coronary Syndrome Safety Profile of Dabigatran Etexilate in Patients Undergoing Major Orthopedic Surgery
Introduction: Stopping anticoagulant therapy may lead to increased cardiovascular events via a so called ‘rebound phenomenon’. We studied the incidence of acute coronary syndrome (ACS) events during the treatment and post-treatment periods in patients undergoing major orthopedic surgery and treated with either the oral direct thrombin inhibitor dabigatran etexilate (DE) or enoxaparin.
Methods: Patients in the RE-MODEL, RE-NOVATE and RE-MOBILIZE trials were randomized to receive DE 150 mg (n=2737) or 220 mg (n=2682) once daily, or enoxaparin (n=2716) for 6-35 days and were followed for 90 days post-surgery. ACS during treatment and follow-up were identified based on investigator reports. In addition, a blinded, independent, central assessment of predefined trigger events was performed for the robust identification of adverse cardiac and arterial events using pre-specified Medical Dictionary for Regulatory Authorities (MedDRA) trigger terms relating to locally-diagnosed ACS, as well as a broader MedDRA term list that could reflect undiagnosed ACS. Adjudicated events were categorized as definite, likely, unlikely or not ACS.
Results: During treatment, investigator-reported ACS events occurred in 4 patients (0.1%) in the DE 220 mg group, 14 (0.5%) in the DE 150 mg group and 11 (0.4%) in the enoxaparin arm. Post-treatment events occurred in 1 (<0.1%), 1 (<0.1%), and 4 patients (0.2%) in the 3 groups, respectively. By blinded central adjudication, definite/likely ACS events occurred during treatment in 16 (0.6%) and 26 (0.9%) patients on DE 220 mg and 150 mg, respectively, compared with 20 (0.7%) on enoxaparin. Central adjudication identified definite/likely post-treatment ACS events in 2 (<0.1%) patients after DE 220 mg, 2 (<0.1%) following DE 150 mg, and 7 (0.3%) after enoxaparin. No between-group differences were statistically significant.
Conclusions: Whether identified through local investigator reporting or blinded central adjudication, no significant differences in ACS rates were detected among orthopedic surgery patients treated with DE compared with enoxaparin during or after treatment. Overall event rates were low, without evidence of a clinically significant “rebound” effect for either agent in this post-surgical population.
- © 2011 by American Heart Association, Inc.