Results from clinical trials on ST-elevation myocardial infarction in a historic perspective with some pathophysiological aspects

OBJECTIVE: Since the publication of the large trials on streptokinase and aspirin improving mortality related to an acute ST-elevation myocardial infarction (STEMI) there has been numerous studies on improving treatment results with new fibrinolytics, adjuvant heparin therapy and primary percutaneous intervention (PCI). The aim of the present overview is, in a historic perspective, to link some of the pathophysiology of mechanisms related to plaque rupture and following thrombosis to the effects of drug combinations and PCI observed in major clinical trials conducted in patients with STEMI. DESIGN: The overview comprises short analyses of the initial streptokinase trials (GISSI-1 and ISIS-2), the comparisons between streptokinase and tissue plasminogen activator (rt-PA) and the role of adjuvant heparin treatment (GISSI-2, ISIS-3, GUSTO I). Also included is the comparison between the new bolus-teplases and traditional, accelerated infusion of rt-PA (GUSTO III and ASSENT-2) and between unfractionated heparin (UFH) and low molecular weight heparin (LWMH) given in addition to tenecteplase (ASSENT-3). The pathophysiology of the antiplatelet and antithrombin effects is described, in order to elucidate the treatment differences observed in the trials. In addition, the role of primary PCI is discussed in view of the results in a recent meta-analysis of controlled comparisons with fibrinolytic therapy. RESULTS: Based upon these trials it seems that the optimal thrombolytic treatment is a combination of a bolus-teplase (tenecteplae) and LMWH given on top of aspirin. Primary PCI may be the most optimal treatment, provided given early following STEMI (<1 h), but whether PCI is the best alternative for all patients with STEMI is still a matter of debate. CONCLUSION: During the last 15 years the optimal antithrombotic treatment of STEMI has developed from a combination of streptokinase and aspirin to the new bolus-teplases combined with LMWH and aspirin. The use of primary PCI may be a better alternative than fibrinolytic therapy, but such a statement needs confirmation in a large comparison between PCI and a quick infusion of modern fibrinolytic agents.