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Confronting the Challenge of Acute Coronary Syndromes

Michel E. Bertrand, M.D., F.R.C.P., F.E.S.C., F.A.C.C., and Eugene Braunwald, A.B., M.D., M.S. (Hon), M.D. (Hon)*

Department of Cardiology, Université de Lille, Hôpital Cardiologique, Lille, France; *Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA

Previously presented at the XVIIIth Congress of the European Society of Cardiology, Birmingham, England, 1996. Supported by a grant from Schering-Plough International.

Introduction

Acute coronary syndromes (ACS), which include unstable angina, non-Q-wave myocardial infarction (MI), Q-wave MI, and the acute complications resulting from interventional procedures, continue to be the leading cause of morbidity and mortality in Western countries. Although current management strategies for patients with ACS, including fibrinolytics, anticoagulants, and antiplatelet agents, have demonstrated clinical benefit, morbidity and mortality rates remain significant. Fourteen percent of all deaths in Western European countries (414,000 annually) have been attributed to ischemic heart disease. In the United States, ACS account for approximately 500,000 deaths each year.

Cumulative evidence strongly argues for the pivotal role of platelet aggregation and coronary thrombosis in the pathophysiology of both ACS and ischemic complications of percutaneous interventions. Activation and cross-linking of the platelet glycoprotein (GP) IIb-IIIa receptor represent the final common pathway to platelet aggregation, and several inhibitors of this receptor have recently been developed as a potentially more effective way to manage coronary thrombosis.

Phase III trials of GP IIb-IIIa receptor inhibitors, such as abciximab and eptifibatide (Integrilinú), have demonstrated the benefit of these therapies in patients at risk for ischemic complications following scheduled percutaneous transluminal coronary angioplasty (PTCA). These promising results suggest that GP IIb-IIIa receptor inhibition may become a valuable new strategy for managing thrombotic complications of PTCA. Additional trials are expected to demonstrate the benefit of GP IIb-IIIa inhibitors as the primary and/or adjunctive therapy for the whole spectrum of ACS and may lead to the inclusion of these agents in the standard management of such patients.

This supplement is the published proceedings of a symposium entitled Confronting the Challenge of Acute Coronary Syndromes, organized by Schering-Plough International during the XVIIIth Congress of the European Society of Cardiology on August 25, 1996, in Birmingham, England.

The first article in the supplement, The Role of Plaque Pathology in Coronary Thrombosis, by Prof. Michael J. Davies, discusses the development and clinical presentation of ACS, including the pathophysiology of the disruption of atherosclerotic plaque and the superimposed formation of the platelet-rich thrombus, leading to occlusion of coronary circulation.

The second article, by Prof. Karl Ludwig Neuhaus, entitled Coronary Thrombosis–Defining the Goals, Improving the Outcome, addresses the clinical benefits and shortcomings of the current pharmacologic treatment of ACS, involving antithrombotic therapy with heparin and aspirin, and the novel approach to management of ACS through inhibition of platelet aggregation, the key event in the pathogenesis of ACS.

The third article, entitled The Benefits and Risks of Coronary Intervention – Balancing the Equation, by Dr. Pim J. de Feyter, examines current management and outcome of patients with ischemic heart disease and the substantial improvements achievable by (1) appropriate assessment of their risk for complications during and immediately following angioplasty and (2) development of more effective adjunctive antithrombotic therapies.

The final article, by Dr. Eric J. Topol, entitled Targeted Approaches to Thrombus Inhibition–An End to the Shotgun Approach, reviews the effectiveness of current approaches to prevention of coronary thrombus formation and points to future directions in the treatment of ACS, specifically GP IIb-IIIa receptor inhibitors, and the clinical benefits demonstrated by these agents in advanced clinical trials.