Fibrinolysis for acute myocardial infarction: current status and new horizons for pharmacological reperfusion, part 1.

No treatment has had more profound impact on the global management of patients with acute ST-segment elevation myocardial infarction than fibrinolytic therapy. The ability to achieve rapid and effective coronary reperfusion pharmacologically with a systemic intravenous bolus or infusion has truly transformed our therapeutic approach. Since this subject was last reviewed in 1998 in the New Frontiers Section of Circulation , there have been 2 additional fibrinolytic agents released for clinical application and 1 other that has undergone major and extensive phase 2 and 3 investigation.1 Although streptokinase (SK), recombinant tissue plasminogen activator (rt-PA), and more recently reteplase (r-PA) are in general clinical use, there remains some dissatisfaction with their overall efficacy. This relates in part to the failure to achieve optimal tissue reperfusion in approximately one half of patients so treated, as well as persistent risks associated with systemic hemorrhagic effects, some of which complicate ancillary vascular interventional procedures in complicated patients. The risk of intracranial hemorrhage, affecting 5 to 10 of 1000 patients treated, remains a dreaded complication.2 In this review, we examine (1) the evolution of the development of fibrinolytics; (2) the pharmacology, pharmacokinetics, and pharmacodynamics of available agents; (3) the need for ancillary therapy; (4) the clinical indications, benefits and risks; (5) the therapeutic alternatives to fibrinolysis; and (6) the future developments that are likely to affect the application of this therapy. Sherry,3 one of the pioneers of fibrinolysis, has provided an instructive historical overview of the earliest origins of thrombolytic therapy, beginning with the recognition of the “fibrinolytic” potential of β-hemolytic streptococci, followed by the demonstration of the capacity of SK to dissolve clotted blood and fibrinous exudates in a patient with a hemothorax. It took an additional 25 years for this discovery to culminate in the application of SK treatment in …