Routine Medical Management of Acute Myocardial Infarction [antikvár]

This reprint is distributed as a professional courtesy by B EH RING WERKE AG, is offered by the American Heart Association solely for educational purposes, and does not constitute an endorsement of products or services by the American Heart Association. Routine Medical Management of Acute Myocardial Infarction Lessons From Overviews of Recent Randomized Controlled Trials Salim Yusuf, MB, DPhil, MRCP, Peter Sleight, DM, FRCP, Peter Held, MD, PhD, and Stephen McMahon, PhD, MPH In recent years, several large randomized trials have clarified the role of various interventions in acute myocardial infarction. There is clear evidence that thrombolytic therapy, aspirin, and ^-blockers reduce mortality. Both aspirin and /3-blockers also reduce reinfarction and stroke. Of the thrombolytic agents, comparative trials have established that tissue plasminogen activator and streptokinase have similar effects on mortality, morbidity, and left ventricular function. There appears to be an increased risk of cerebral hemorrhage with tissue plasminogen activator. The benefits of heparin in conjunction with aspirin and a thrombolytic agent are unclear and, at best, are likely to be modest. Heparin increases the risk of hemorrhagic complications twofold. Although trials of vasodilators conducted before the widespread use of thrombolytic therapy and aspirin have been promising, newer trials are needed to evaluate their effects among patients receiving these agents. The aggregate of all trials of the routine use of calcium antagonists or antiarrhythmic agents indicates that these agents do not improve survival. (Circulation 1990;82(suppl II):II-117-II-134) During the last decade, emphasis on the management of patients with acute myocardial infarction (AMI) has shifted from approaches focused largely on the prevention or management of malignant arrhythmia to strategies aimed at reducing the extent of infarction, preventing reinfarction, and promoting myocardial healing. This change in emphasis has been due, in part, to better understanding of the factors influencing the course of experimental and clinical infarction and, in part, to our increasing ability to evaluate reliably the benefit-risk ratio of new interventions in large well-designed randomized clinical trials. This article reviews pharmacological interventions in AMI and does not review the trials of percutaneous transluminal coronary angioplasty (PTCA). Despite its theoretical appeal, all the trials of routine PTCA have consistently failed to demonstrate benefit; in From the Clinical Trials Branch, Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute Bethesda, Md (S.Y., P.H.), the Cardiac Department, John Rad-cliffe Hospital, Oxford, England (P.S.), and the Clinical Trials Research Unit, Department of Medicine, University of Auckland, New Zealand (P.S.). Address for correspondence: Salim Yusuf, MB, DPhil, MRCP, Clinical Trials Branch, Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, MD 20892. fact, there is a trend toward increased mortality and morbidity in several trials of routine PTCA.1-3 The results of these trials have been reviewed by Ryan4 in this supplement. Rationale for Interventions in Acute Myocardial Infarction Deaths in patients after AMI are usually due to one or more of the following causes: 1) Large infarcts that lead to deteriorating pump function and secondary arrhythmias, 2) primary or drug-induced ventricular tachyarrhythmias or asystole, 3) cardiac rupture, 4) reinfarction, and 5) infarct expansion and ventricular dilatation. Deaths after AMI might therefore be reduced by any one of a number of potential interventions. The size of an infarct can be reduced by improving the balance between oxygen supply and demand through increasing myocardial blood flow (dissolving an obstructing clot or improving collateral blood flow) or by reducing oxygen demand by reducing cardiac work. Antiarrhythmic drugs could be used to decrease the risk of death due to arrhythmias although these drugs may themselves confer an increased risk of asystole and heart block. Some antiarrhythmic agents are known to have a negative inotropic effect and may even exacerbate arrhythmias. Cardiac rupture and arrhythmias might be