Acylated plasminogen-streptokinase activator complex: a new approach to thrombolytic therapy.

Acylated plasminogen-streptokinase activator complex (APSAC; antistreplase) is an inactive complex of human plasminogen and streptokinase. When it is injected, a controlled deacylation of the catalytic center occurs, activating the complex so that thrombolysis may begin. This process extends the half-life of streptokinase, allowing for 4-6 hours of fibrinolytic activity. Anistreplase has demonstrated equivalent efficacy to intracoronary streptokinase with regard to reperfusion rates in acute myocardial infarction. In addition, patients have shown a 56% reduction in mortality at 28 days with anistreplase compared to heparin. The adverse effect profile of anistreplase includes minor bleeding and hematoma formation at the site of venipuncture, hypotensive and bradycardic episodes, arrhythmias, facial flushing, fever, and rarely, allergic reactions. Serious bleeding reactions are uncommon, with the frequency of cerebrovascular accident reported at 0.4-0.6%. The special advantage of anistreplase is its administration as a 30-U intravenous bolus injected over 5 minutes, eliminating the need for long infusions and increasing the ease of administration. Based on its efficacy and ease of administration, anistreplase may become the drug of choice in the emergency treatment of acute myocardial infarction.

Use of a proprietary database to examine lengths of hospital stay of patients who received drug therapy for acute myocardial infarction.

Lengths of hospital stay of patients who received streptokinase therapy and of patients who received conventional i.v. heparin or nitroglycerin therapy for acute myocardial infarction (AMI) were determined using the International Health Services, Ltd., (IHS) database. Patients in all IHS-participating hospitals who had received streptokinase in conjunction with an AMI between October 1985 and September 1986 were identified from the database. Diagnosis-related groups (DRGs) 121 and 122 were found to contain patients who potentially could serve as the study population. Based on examination of length-of-stay data from the medical record database at the study hospital, the IHS study population was refined to include AMI patients 75 years of age or younger with stage 2 disease (intermediate severity) in DRG 121 or stage 1 disease (least severe) in DRG 122 and a length of stay of at least seven days. Patients who met those criteria and had been treated with heparin, nitroglycerin, or both served as a control group. The mean length of stay of patients treated with streptokinase (113 patients) was significantly shorter than that of patients treated with heparin (1332 patients) or nitroglycerin (752 patients). Patients treated with streptokinase had a length of stay 1.2 days shorter than patients treated with heparin and 1.3 days shorter than patients treated with nitroglycerin. The database proved to be useful for determining lengths of patient stay associated with thrombolytic and conventional medical therapy for AMI. Thrombolytic therapy may be a cost-effective treatment for AMI because length of stay may be somewhat shorter.

Tissue plasminogen activator: a new thrombolytic agent.

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, contraindications, and dosage and administration of tissue plasminogen activator are reviewed. Tissue plasminogen activator (t-PA) is a serine protease that binds to fibrin-plasminogen complex, catalyzing the conversion of plasminogen to plasmin. Unlike streptokinase or urokinase, t-PA binds slowly, if at all, to free circulating plasminogen. This clot specificity suggests t-PA will not produce a systemic lytic effect; however, clot specificity appears to be dose-related, and concentrations similar to those achieved in recent clinical trials have been associated with hemostatic defects. Most clinical trials have used a recombinant DNA product (rt-PA). In the treatment of acute myocardial infarction, intravenous infusions of rt-PA appear to be more effective than intravenous streptokinase. Similar rates of hemorrhage, reperfusion arrhythmias, and reocculsion have been reported. Contraindications to rt-PA use are similar to those for other thrombolytic agents. Preliminary studies of rt-PA in various thromboembolic disorders are encouraging. Marketing approval of a t-PA product (rt-PA, Activase, Genentech, Inc.) is expected in the United States by mid-1987. Clinical trials suggest that rt-PA is more effective and as safe as intravenous streptokinase in lysing occlusive coronary-artery thrombi; however, safety and efficacy appear to be dose-related, and further study is needed to determine the optimal dose.