Current Thrombolytics

Streptokinase entered clinical use in the mid-1940s. The first use of a fibrinolytic drug in the treatment of acute myocardial infarction was reported in 1958, when intravenous infusion of streptokinase was used.31 Shortly after that, in 1960, streptokinase and human plasmid were injected into the aortic root of a man following myocardial infarction.32 However, the revolution of thrombolytic therapy started in 1976 in Russia, with direct intracoronary injection of fibrinolysin.33 Several trials followed and it was soon recognized that early restoration of the blood flow preserved left ventricular function and yielded significant mortality benefit. However, the use of intracoronary therapy was limited, because it was time consuming and needed specially equipped hospitals and well-trained personnel.

t-PA and high-dose intravenous streptokinase became established as a life-saving treatment for acute myocardial infarction (MI),34 and were approved for use by the US Food and Drug Administration (FDA) in the mid-1980s. Trials to establish the efficacy of streptokinase for acute ischemic stroke were stopped because of a high rate of early death due to intracerebral hemorrhage. In 1996, the FDA approved intravenous thrombolysis with rt-PA as the 'first-ever' effective treatment for ischemic stroke during the first 3 h of onset of symptoms.36 Reteplase was the first of the third-generation thrombolytics to be approved for use in acute MI.35

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