The promise of new genetically engineered plasminogen activators

The therapeutic efficacy of thrombolytic therapy for the treatment of acute myocardial infarction was first demonstrated convincingly in 1985 by the GISSI investigators. In the ensuing 10 years, continued clinical investigation has focused on improving the safety and efficacy of thrombolytic therapy. In addition to the use of adjunctive agents such as inhibitors of platelet aggregation and thrombin, new genetically engineered "second-generation" thrombolytic agents have been developed that offer the promise of improved clinical outcomes. The availability of these potent agents for clinical investigation offers the opportunity to determine the importance of properties such as fibrin specificity, plasma half-life, and resistance to inhibition. This review focuses on theoretical and practical aspects of optimizing thrombolytic therapy, survey of new agents on the clinical horizon, and the potential application of these agents for the treatment of patients with thrombotic occulusion of either coronary or peripheral arteries.