The paradigm shift in 1980 on the causation of acute myo-cardial infarction to acute coronary occlusion by a thrombus created the rationale for thrombolytic therapy of this com-mon lethal disease. At that time—and for the first time— intravenous thrombolytic therapy for acute myocardial infarction in the European Cooperative Study Group trial was found to reduce mortality. Later studies, with thousands of patients in each trial, provided enough statistical power for the 20% reduction in mortality to be considered statisti-cally significant. Although the standard of care in areas with adequate facilities and experience in percutaneous coronary intervention (PCI) now favors catheterization and placement of a stent, thrombolytic therapy is still very important where PCI is not readily available. The proper selection of patients for thrombolytic therapy is critical. The diagnosis of acute myocardial infarction is made clinically and is confirmed by electrocardiography. Patients with ST-segment elevation and bundle branch block on electrocardi-ography have the best outcomes. All trials to date show the great-est benefit for thrombolytic therapy when it is given early, within 6 hours after symptomatic onset of acute myocardial infarction. Thrombolytic drugs reduce the mortality of acute myocardial infarction. The early and appropriate use of any thrombolytic drug probably transcends possible advantages of a particular drug.
Plasminogen can also be activated endogenously by tissue plasminogen activators (t-PAs). These activators preferentially activate plasminogen that is bound to fibrin, which (in theory) confines fibrinolysis to the formed thrombus and avoids systemic activation. Recombinant human t-PA is manufactured as alteplase. Reteplase is another recombinant human t-PA from which several amino acid sequences have been deleted. Tenecteplase is a mutant form of t-PA that has a longer half-life, and it can be given as an intravenous bolus. Reteplase and tenecteplase are as effective as alteplase and have simpler dosing schemes because of their longer half-lives.
Administration of fibrinolytic drugs by the intravenous route is indicated in cases of pulmonary embolism with hemodynamic instability, severe deep venous thrombosis such as the superior vena caval syndrome, and ascending thrombophlebitis of the iliofemoral vein with severe lower extremity edema. These drugs are also given intra-arterially, especially for peripheral vascular disease.
Thrombolytic therapy in the management of acute myocardial infarction requires careful patient selection, the use of a specific thrombolytic agent, and the benefit of adjuvant therapy. Streptokinase is administered by intravenous infusion of a loading dose of 250,000 units, followed by 100,000 units/h for 24–72 hours. Patients with antistreptococcal antibodies can develop fever, allergic reactions, and therapeutic resistance. Urokinase requires a loading dose of 300,000 units given over 10 minutes and a maintenance dose of 300,000 units/h for 12 hours. Alteplase (t-PA) is given as a 15-mg bolus followed by 0.75 mg/kg (up to 50 mg) over 30 minutes and then 0.5 mg/kg (up to 35 mg) over 60 minutes. Reteplase is given as two 10-unit bolus injections, the second administered 30 minutes after the first injection.