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Vol. 22, Supplement IV

Breaking the Therapeutic Barriers: New Strategies for Acute Coronary Syndromes

Christopher P. Cannon, M.D.
Guest Editor

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This supplement was based in part on Thrombolysis '98, a symposium held in November 1998 and broadcast on This supplement, as was the symposium, was sponsored by an unrestricted educational grant from Centocor, Inc.

Chest Pain Emergency Centers: Improving Acute Myocardial Infarction Care (Download in PDF)

J. P. Ornato, M.D.

Uncertainty and delay are common in the diagnosis of acute coronary syndromes (ACS). In the last 20 years, the need for faster, more accurate, and more cost-effective diagnosis gave rise to the concept of specialized treatment of patients with chest pain in emergency departments (EDs). The original strategy dedicated a separate section of the ED and a nursing staff to the task of rapid intervention in patients with acute myocardial infarction (MI) and triage of low-risk patients. Chest pain centers grew quickly in popularity but evolved with a variety of goals, staffing plans, diagnostic resources, and levels of commitment. Three existing centers--the University of Cincinnati Heart ER, Brigham and Women's Hospital, and the Medical College of Virginia--have implemented chest pain strategies with the common aims of (1) screening for the entire spectrum of coronary artery disease, (2) avoiding unnecessary admissions, and (3) using multiple diagnostic modalities. Yet, they differ in the specifics of their approaches and diagnostic methods (e.g., echocardiography vs. treadmill vs. myocardial perfusion imaging). The safety and cost effectiveness of these centers are discussed.

Prehospital Thrombolysis: An Idea Whose Time Has Come (Download in PDF)

C. P. Cannon, M.D., A. J. Sayah, M.D., R. M. Walls, M.D.

Aggressive reperfusion therapy for myocardial infarction (MI) characterized by acute ST-segment elevation leads to improved patient outcome. Furthermore, use of thrombolytic therapy is highly time-dependent: reperfusion therapy is beneficial within 12 h, but the earlier it is administered, the more beneficial it is. Thus, the focus of both prehospital and emergency department management of patients with acute MI is on rapid identification and treatment. There are many components to the time delays between the onset of symptoms of acute MI and the achievement of reperfusion in the occluded infarct-related artery. Time delays occur with both the patient and the prehospital emergency medical system, although patient delays are more significant. This article focuses on the prehospital management of acute MI, including (1) the rationale for rapid reperfusion in patients with acute MI, (2) the factors related to time delays in patient presentation to the hospital, and (3) strategies for reducing time delays, both patient- and medical system-based.

Reperfusion Revisited: Beyond TIMI 3 Flow (Download in PDF)

J. P. Gassler, M.D. and E. J. Topol, M.D.

Therapy for acute myocardial infarction has advanced dramatically since the early 1980s with the use of early intravenous fibrinolytic therapy. Combining low-dose fibrinolysis and platelet lysis appears to provide an additional increase in infarct-related artery patency, but the large-scale mortality reduction trials evaluating this strategy are just getting under way. Recently, considerable attention has shifted away from the epicardial arteries to the microvasculature. Contemporary evidence suggests that epicardial patency does not necessarily translate to actual perfusion at the myocardial level. Techniques to evaluate beyond thrombolysis in myocardial infarction (TIMI) epicardial flow are now available and validated. In addition, we have promising treatments for the prevention or alleviation of certain forms of microvascular obstruction. This review attempts to clarify the confusion surrounding epicardial flow and "myocardial malperfusion" and to provide some insight into the next direction in acute myocardial infarction therapeutics.

Incorporating Platelet Glycoprotein IIb/IIIa Inhibition in Critical Pathways: Unstable Angina/Non–ST-Segment Elevation Myocardial Infarction (Download in PDF)

C. P. Cannon, M.D.

Platelet glycoprotein (GP) IIb/IIIa inhibitors have been shown to be effective in reducing thrombotic events in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI) and when used as medical therapy in patients with unstable angina/non–ST-segment elevation myocardial infarction (MI). Recent findings include dramatic preventive benefits in the setting of coronary stent deployment and a significant long-term preventive effect on mortality. The benefits of GP IIb/IIIa receptor inhibition suggest the utility of adopting routine use of these agents in critical pathways for unstable angina/non–ST-segment elevation MI and PCI. Because cost constraints may limit use of these agents, however, targeting treatment based on patient risk assessment may be warranted.

Combination Therapy for Acute Myocardial Infarction: Glycoprotein IIb/IIIa Inhibitors plus Thrombolysis (Download in PDF)

C. P. Cannon, M.D.

Although thrombolytic therapy has been a major advance in the treatment of acute ST-segment elevation myocardial infarction (MI), new thrombolytic agents have been unable to improve early reperfusion. Because aspirin has been shown to be a very effective adjunctive agent in patients with acute MI, it has been hypothesized that the use of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors combined with thrombolytic agents would lead to more effective platelet inhibition and improved angiographic and clinical efficacy. Emerging experimental and clinical data, including the Thrombolysis in Myocardial Infarction (TIMI)-14 trial, suggest that combining GP IIb/IIIa receptor inhibition with reduced-dose thrombolytic therapy improves early infarct-related artery patency without increasing bleeding risk. Thus, given the strong clinical and physiologic rationale, clinical investigation in patients with acute ST-segment elevation MI is currently focused on combining GP IIb/IIIa receptor inhibitors with reduced-dose fibrinolytic agents in acute MI.

Future Directions in Thrombolysis (Download in PDF)

J. T. Willerson, M.D. and P. Zoldhelyi, M.D.

An extensive body of research conducted in the past 25 years has helped foster understanding of the mechanisms and pathogenesis of the acute coronary syndromes and occlusive disease. Thus, it is well established that thrombosis is caused by vascular injury and that immediate lysis of the arterial thrombus and subsequent prevention of thrombotic reocclusion are critical to the treatment of these disorders. Remarkable progress in the understanding of the biological and molecular mechanisms involved in vascular-wall–platelet interactions, platelet–platelet interactions, and coagulation has led to the identification of multiple targets for drug discovery and the development of numerous antithrombotic drugs. The purpose of this article is to review emerging antithrombotic therapies, introduce potential future molecular targets for drug discovery efforts, and discuss novel strategies for managing patients with coronary disease.