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INTRODUCTION

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Acute coronary syndromes (ACS), including non ST-elevation (NSTE) ACS (unstable angina [UA]/non–ST-segment elevation myocardial infarction [NSTEMI]), and ST-segment elevation myocardial infarction (STEMI), represent the clinical complications of atherosclerosis mediated by plaque rupture, fissure and superficial endothelial cell erosion that produce nonocclusive and occlusive thrombus formation.1,2,3 NSTEMI accounts for more than 1.6 million annual admissions, representing up to 75% of all cases of myocardial infarction (MI) in US hospitals.4 Appropriate care for patients with ACS is informed by a wealth of randomized controlled trials, the findings of which have been summarized into national clinical practice guidelines by the American College of Cardiology (ACC)/American Heart Association (AHA)4,5,6 and the European Society of Cardiology (ESC).7,8,9 This chapter will review the pharmacology of antiplatelet, anticoagulant, and fibrinolytic agents and also focus on evidence-based recommendations for the use of antithrombotic therapy in ACS. Given the evolving understanding of the prognostic implications, including mortality, associated with the most important adverse effect associated with antithrombotic agents (ie, bleeding), an assessment of the net clinical benefit of a particular antithrombotic agent—namely, balancing efficacy and safety—will be elaborated.10,11,12,13,14 Bleeding complications are secondary to multiple factors including impaired oxygen delivery, adverse effects of transfusion (ie, proinflammatory, old vs new blood), and cessation of antithrombotic medications.10,11,12,13,14 There are important sex- and age-related factors that promote bleeding as a result of excessive dosing.15,16 Understanding the trade-off between reduction of ischemic events (ie, recurrent MI, stent thrombosis, stroke) and risk of bleeding complications associated with antithrombotic agents is essential for the practicing clinician. Recommendations from the most recent guideline updates will also be provided. Importantly, guideline adherence rate is significantly associated with in-hospital mortality. In an observational analysis of hospital care in 350 academic and nonacademic US centers of 64,775 patients enrolled in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) trial, every 10% increase in composite adherence at a hospital was associated with an analogous 10% decrease in its patients’ likelihood of in-hospital mortality.17 Thus, a thorough knowledge of pharmacologic therapy and guideline-recommended treatments is the foundation for optimizing outcomes for patients with ACS.

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ANTITHROMBOTIC THERAPY: GENERALITIES

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Arterial thrombosis following atherosclerotic plaque complications is the major determinant of ACS.18 Plaque rupture, fissure, or erosion, with exposure of the subendothelium, leads to recruitment and activation of platelets, as well as generation of thrombin, which leads to the formation of a fibrin-rich thrombus. A nonocclusive or transiently occlusive thrombus most frequently characterizes patients with a NSTE-ACS, which include UA and NSTEMI.18 More stable and occlusive thrombus prevails in STEMI.18 Platelet-activated thrombosis follows three main steps: (1) platelet adhesion, (2) platelet activation and additional recruitment, and (3) ...

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