Standardized Bleeding Definitions for Cardiovascular Clinical Trials

Abstract

Advances in antithrombotic therapy, along with an early invasive strategy, have reduced the incidence of recurrent ischemic events and death in patients with acute coronary syndromes (ACS; unstable angina, non–ST-segment–elevation myocardial infarction [MI], and ST-segment–elevation MI).1,–,4 However, the combination of multiple pharmacotherapies, including aspirin, platelet P2Y12 inhibitors, heparin plus glycoprotein IIb/IIIa inhibitors, direct thrombin inhibitors, and the increasing use of invasive procedures, has also been associated with an increased risk of bleeding. Editorial see p 2664 Bleeding complications have been associated with an increased risk of subsequent adverse outcomes, including MI, stroke, stent thrombosis, and death, in patients with ACS and in those undergoing percutaneous coronary intervention (PCI),5,–,10 as well as in the long-term antithrombotic setting.11,12 Thus, balancing the anti-ischemic benefits against the bleeding risk of antithrombotic agents and interventions is of paramount importance in assessing new therapies and in managing patients. Prior randomized trials comparing antithrombotic agents suggest that a reduction in bleeding events is associated with improved survival.13,14 Because prevention of major bleeding may represent an important step in improving outcomes by balancing safety and efficacy in the contemporary treatment of ACS, bleeding events have been systematically identified as a crucial end point for the assessment of the safety of drugs during the course of randomized clinical trials, and are an important aspect of the evaluation of new devices and interventional therapies.15 Unlike ischemic clinical events (eg, cardiac death, MI, stent thrombosis), for which there is now general consensus on end-point definitions,16,17 there is substantial heterogeneity among the many bleeding definitions currently in use. Lack of standardization makes it difficult to optimally organize key clinical trial processes such as adjudication, and even more difficult to interpret relative …