The Therapy of Acute Myocardial Infarction: Current State of the Art

Summary

For decades management of acute myocardial infarction (AMI) consisted of bed rest, oxygen, prevention for thromboembolic complications, and treatment of arrhythmias and heart failure. In the last years a more aggressive treatment of AMI has been developed, based on the following three basic principles:

(1) Mortality of patients with AMI is determined by the infarct size and the degree of left ventricular dysfunction. (2) The time interval between the onset of coronary occlusion and any intervention to limit infarct size is brief and takes usually not more than three to four hours. (3) After the acute phase of infarction a lot of patients remain at high risk of fatal coronary events, i.e. reinfarctions.

The angiographic findings during the first hours of AMI showed in about 80% of patients an obstructive coronary thrombus and led to efforts to dissolve the offending thrombi. The demonstration that coronary thrombi can be lysed in about 80% of cases within 60 minutes after the intracoronary injection of thrombolytic agents (Streptokinase or Urokinase) has boosted the reperfusion therapy in AMI in the hope that ischemic myocardium might be salvaged. Intracoronary infusion of thrombolytic agents however, can be applied only in a minority of patients with AMI because coronary angiography and a skilled team of investigators are required, therefore a short-time intravenous high dose Streptokinase infusion was developed. In the meantime two large double blind randomized trials (ISAM and GISSI) could demonstrate a reduction in hospital mortality in AMI especially by early treatment with intravenous streptokinase. Conventional thrombolytic agents produce a systemic lytic State with the possibility of hemorrhage, therefore recombinant tissuetype Plasminogen activator (rt-PA) and two other drugs, acylated Streptokinase and pro-urokinase, were developed with the aim of inducing coronary thrombolysis without severe systemic lytic State, but the efficacy of these new drugs remains to be demonstrated in randomized trials versus conventional thrombolytic agents. Emergency penetration of a coronary thrombus by percuteneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) may also be used as the primary approach to reperfusion of the ischemic myocardium in patients with AMI, but in contrast to these invasive techniques only intravenous thrombolytic therapy can probably be applied within four hours of the onset of AMI in the majority of patients. The successful early reperfusion of evolving infarction with limitation of infarct size should be secured by early PTCA or CABG.

The optimal approach in patients with AMI for limitation of infarct size might consist of the following therapeutic strategy: (1) prophylactic chronic treatment with beta-adrenergic blocking agents or calcium antagonists to slow myocardial necrosis in the event of coronary occlusion; (2) intravenous infusion of a thrombolytic drug to reperfuse the ischemic myocardium; (3) follow-up coronary angiography with the necessity of PTCA or CABG to prevent rethrombosis and to reduce the risk of reinfarction.

Zusammenfassung

Unter der Überlegung, die Infarktmortalität dadurch zu reduzieren, daß eine Begrenzung der Infarktausdehnung erreicht wird, werden neuere Gesichtspunkte der Pathogenese des akuten Myokardinfarktes beleuchtet. Da es sich in 80% der Fälle immer um einen akuten thrombotischen Koronarverschluß auf dem Boden einer stenosierenden Koronarsklerose handelt, bemüht man sich seit ca. 10 Jahren darum, möglichst frühzeitig durch die Applikation verschiedener thrombolytischer Substanzen den Koronarverschluß zu beseitigen. Aufgrund tierexperimenteller Befunde muß heute angenommen werden, daß eine Reperfusionsbehandlung nur dann erfolgreich ist, wenn die Ischämiezeit 3-4 Stunden nicht überschreitet. Es wird in diesem Zusammenhang über zwei Therapiestudien, die ISAM- Studie und die GISSI-Studie, im einzelnen berichtet. Des weiteren werden neuere Therapiekonzepte mit Plasminogen-Aktivator und hochdosierter Urokinasegabe diskutiert. Schließlich wird ein Behandlungsplan des akuten Myokardinfarktes vorgelegt, dessen Anfang möglichst bereits vor der Klinikeinweisung - in der häuslichen Umgebung oder im Notarztwagen - liegen sollte. In diesem Therapieschema wird dann weiter der Platz der akuten Koronarangiographie, der Ballon-Dilatation und der Bypass-Operation festgelegt.

Key words

Acute myocardial infarction - Thrombolytic therapy - Percutaneous transluminal coronary angioplasty - Aorto-coronary bypass surgery