Evaluating the need for a practical risk score to predict major bleeding in acute coronary syndromes

Abstract

The incidence of recurrent adverse ischemic events and death after acute coronary syndromes (ACS): unstable angina, ST-segment elevation myocardial infarction [STEMI] and non-STEMI [NSTEMI]) has been significantly reduced by advances in antithrombotic therapy and invasive treatment strategies [1–4]. However, the use of multiple antiplatelet agents (i.e., aspirin, P2Y12 inhibitors, and glycoprotein IIb/IIIa inhibitors [GPIs]) and antithrombotic therapies (i.e., unfractionated heparin [UFH], lowmolecular weight heparin, factor-Xa inhibitors and direct thrombin inhibitors), in combination with an early invasive approach has increased the risk of bleeding. The incidence of hemorrhagic complications after treatment of ACS ranges from 1 to 10%, depending on differences in patient characteristics, antithrombotic therapies, timing of event reporting and bleeding definitions [5–8]. Despite this heterogeneity, numerous studies have demonstrated that bleeding is associated with an increased risk for both shortand long-term adverse outcomes [5,7–12]. Although the exact mechanisms causing this increased risk after bleeding complications are not fully understood, a number of factors are likely to contribute, such as the cessation of evidence-based therapies (i.e., antiplatelet agents, b-blockers and statins) in patients who bleed, adverse effects of blood transfusion, detrimental effects of acute anemia and a greater prevalence of comorbidities in patients who bleed. In contemporary practice, cardiologists have a wide variety of antiplatelet and antithrombin agents from which to choose. Each individual drug has a different profile of clinical efficacy (suppression of ischemic complications from the ACS event itself, or from the treatments subsequently required, most commonly percutaneous coronary intervention [PCI]) versus complications (principally bleeding). Large randomized clinical trials have demonstrated that treatment strategies that reduce bleeding while effectively suppressing ischemia are associated with improved survival in patients with ACS. The Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS)-5 trial randomized 20,078 patients with non-STelevation ACS to the low-molecular weight heparin enoxaparin or the factor-Xa inhibitor fondaparinux [13]. Fondaparinux was noninferior to enoxaparin in terms of the primary end points of death, myocardial infarction or refractory ischemia at 9 days. Moreover, fondaparinux was associated with significantly reduced rates of major bleeding at 9 days (2.2 vs 4.1%; p < 0.01) and significantly reduced rates of mortality at 30 days (2.9 vs 3.5%; p = 0.02) and 6 months (5.8 vs 6.5%; p = 0.05). The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONSAMI) trial randomized 3602 STEMI patients undergoing primary PCI to treatment with either UFH plus a GPI or the direct thrombin inhibitor bivalirudin. In HORIZONS-AMI, bivalirudin compared with UFH plus a GPI was associated with significantly reduced major bleeding (4.9 vs 8.3%; p < 0.01) at 30-day follow-up, and mortality at 30 days (2.1 vs 3.1%; p = 0.047) and 1 year (3.5 vs 4.8%; p = 0.04) [14,15].