Pharmacoinvasive Therapy in Acute Myocardial Infarction PDF

Preface

Coronary thrombolysis and primary infarct percutaneous coronary intervention (PCI) in the treatment of ST segment elevation myocardial infarction (STEMI) are conventionally viewed as mutually exclusive alternative therapeutic modalities. However, well established principles and a great deal of recently acquired information support the view that the two in combination are synergistic. We shall refer to the combination as "pharmacoinvasive therapy." This terminology emphasizes the notion of synergy and is more descriptively accurate than the often used "facilitated angioplasty." The focus of this book is the conceptual basis underlying pharmacoinvasive therapy and the history of its refinement in the treatment of patients with acute ST segment elevation myocardial infarction.

The development of pharmacoinvasive therapy has not been straightforward. In fact, current clinical research in this area reflects a renaissance of interest in the combined therapeutic approach. Pioneering studies of pharmacologically induced recanalization by Chazov and Rentrop during the 1970s utilized an invasive approach to deliver intracoronary fibrinolytic drugs. Subsequently, intravenously administered fibrinolytic agents proved to be promising. The potential utility of intravenous administration of fibrinolytic agents coupled with prompt, subsequent mechanical recanalization (balloon angioplasty) was recognized and evaluated. However, a high incidence of complications and generally negative results led to a rejection of the use of the two approaches in combination. In addition, they led to the two treatment modalities becoming considered as being mutually exclusive alternatives.

Refinements and improvements in pharmacologic ("thrombolysis") and mechanical approaches ("primary angioplasty") to recanalization have been impressive. Randomized clinical trials and registries have been used to compare and contrast the two, but assessment of both in combination lay dormant until quite recently. Improvements in coronary thrombolysis and coronary interventions now make reassessment of pharmacoinvasive therapy particularly desirable. Reassessment is indicated given the inherent limitations, when used alone, in both pharmacologic (failure to restore flow adequately) and mechanical approaches (unavoidable delay that can prolong the time to initiation of reperfusion).

Section I of this book describes: 1) the conceptual basis underlying pharmacoinvasive therapy, 2) the efficacy and limitations of each of its two components when used alone, and 3) the reductions in mortality that have been accomplished with each. Section II addresses the failure of early trials to demonstrate the benefit of combinations of balloon angioplasty coupled with antecedent coronary thrombolysis.

The PACT trial was a reevaluation of a combined approach. It stimulated further reassessment of combination therapy with the use of registries and substudies in randomized clinical trials. These more recent studies are described in detail in a section devoted to the evolution of pharmacoinvasive therapy.

Subsequent material focuses on the rationale for several studies planned or already underway. These studies are designed to clarify the role of glycoprotein IIB/IIIa inhibitors, low molecular weight heparin, novel anticoagulants, and novel plasminogen activators in facilitating safe and effective initial pharmacologic recanalization while avoiding compromise of benefits that can be conferred by prompt, subsequent percutaneous coronary intervention (PCI).

The last section addresses the design of studies needed to delineate optimal treatment of specific patient populations with STEMI including those at highest risk. One such population is the elderly.

The book concludes with a chapter entitled "Controversy and Convergence." It summarizes the progressive nature of development of refinements in pharmacoinvasive therapy. The chapter emphasizes the underlying principles contributing to the rebirth of interest in this therapeutic modality.

This book was designed to trace the rebirth of pharmacoinvasive therapy attributable to the accomplishments, ingenuity, and diligence of numerous investigators who have been devoted to the care of patients with acute myocardial infarction. The editors are fortunate to have engaged several of these outstanding authorities in presenting their observations, interpretations, and insights.