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Reperfusion therapy for acute myocardial infarction (MI) had its inception with Fletcher et al's1 initial treatise describing the use of intravenous (IV) thrombolytic therapy in patients with thromboembolic disorders, including MI. Shortly after this, Boucek and Murphy2 published their observations of using catheters to deliver fibrinolytic therapy to the aortic root of patients presenting with acute MI, and Favaloro et al3 applied saphenous vein aortocoronary bypass surgery to patients presenting with acute infarction. Two groups, one in Spokane, Washington, and one in Göttingen, Germany, performed emergency catheterization before surgical revascularization for acute MI, and for the first time, knowledge of the coronary anatomy during acute MI became available.4,5 DeWood et al6,7 described the high prevalence of total coronary occlusion in the early hours after acute transmural MI and defined the role of the electrocardiographic (ECG) injury current in identifying a population of patients most likely to have acute total occlusion of the infarct artery and thus most likely to benefit from emergency revascularization.

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In 1978, Rentrop et al8,9 performed emergency guidewire recanalization of an acute thrombotic coronary occlusion and subsequently reported on the first 13 patients with acute MI treated with mechanical reperfusion. These investigators reported their selective catheter infusion of intracoronary streptokinase results at the American Heart Association meetings in 1979, and the modern era of reperfusion therapy was born.10 When the works of DeWood and Rentrop were disseminated, enormous research interest in reperfusion therapy was generated in both Europe and the United States, and a number of randomized trials quickly followed. Khaja et al11 first demonstrated the efficacy of intracoronary streptokinase administration in establishing coronary reperfusion, and the Western Washington investigators12 documented improved survival in patients with acute MI treated with intracoronary streptokinase therapy. Because of the necessity of selective coronary angiography for this treatment, it quickly became apparent that a severe residual stenosis persisted in most patients after successful fibrinolysis. O'Neill et al13 demonstrated that balloon angioplasty could effectively treat the residual stenosis and that this resulted in less recurrent ischemia and better preservation of ventricular function. This report was the first to suggest an advantage of balloon angioplasty over fibrinolytic therapy. Logistical constraints and the limited number of trained operators and catheterization facilities hindered the development of both intracoronary streptokinase and primary angioplasty as reperfusion strategies in the mid-1980s.

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The large GISSI (Gruppo Italiano per lo Studio del la Sopravvivenza nell'Infarto Miocardico) and ISIS (International Study of Infarct Survival)-2 trials,14,15 published in 1984 and 1986, definitively established the efficacy of IV streptokinase in improving survival in patients with acute MI. IV streptokinase with aspirin gained widespread use and became the standard of care as reperfusion therapy for patients with acute MI. Research interest soon focused on the development of new fibrin-specific fibrinolytic drugs that could be administered IV. However, many investigators were still concerned about the severe underlying residual stenosis remaining after ...

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