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 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The insights from the Global Utilization of Streptokinase and t-PA for Occluded Arteries (GUSTO) trial have paved the way for further refinement in myocardial reperfusion strategies. For the moment, there is a better pharmacologic approach for achieving rapid and complete coronary thrombolysis. However, for the future, the legacy from this project is much more meaningful, providing clear-cut validation of the "early open vessel hypothesis" while at the same time exemplifying how deficient our strategies for reperfusion are today. There are explicit signals for persistent, meaningful improvement in the years ahead.
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PMID:Validation of the early open infarct vessel hypothesis. 827 60

Large, controlled clinical trials have conclusively demonstrated that intravenous thrombolytic therapy reduces mortality in patients with acute myocardial infarction. The recently published Global Utilization of Streptokinase and t-PA for Occluded Arteries (GUSTO) study demonstrated that patency within 90 minutes is predictive of survival. As a consequence, the interest in new strategies for enhancing the speed and rate of coronary reperfusion has been renewed. Further improvements in coronary patency can be anticipated by adopting a variety of approaches. Some of these approaches are simple and require only the application of proven principles, whereas others are more complex and require further research. The first approaches include earlier treatment after the onset of clinical symptoms, because of the strong relation between early treatment and improved clinical efficacy. Other approaches include development of more effective dosage regimens for the available thrombolytic agents, development of more fibrin-specific agents in an attempt to speed up lysis, and development of safer, more effective adjunctive antithrombotic agents to accelerate thrombolysis and prevent rethrombosis. The potential benefits from these latter approaches must not be offset by unacceptable increases in major bleeding or in the costs of treatment. The application of proven principles to improve coronary reperfusion should not be obscured by the research of more effective pharmacologic approaches. Actually, earlier and wider use of the currently available thrombolytic agents could potentially save more lives than the development of technically more exciting new approaches.
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PMID:New strategies for enhancing the speed and rate of coronary reperfusion. 827 62

We carried out a prospective survey of the outcome of patients with 'suspected myocardial infarction', in order to determine where they should be nursed. The delay between onset, admission, transfer to the CCU, the sequelae and side-effects of thrombolytic therapy were noted and were documented prospectively. Of 217 admissions to CCU with a history of chest pain and suspected acute myocardial infarction during a four-month period (mean age was 62.8 years range 31 to 86 years) 202 fulfilled the criteria for suspected myocardial infarction. Streptokinase was given in 129 and alteplase in one patient. The delay between onset of pain and admission was < 4 h in 73, 4 to 12 h in 30 and > 12 h in 23. Elderly patients were just as likely as younger ones to receive thrombolytic therapy (Chi 2 = 3.6; P = 0.6). An eventual diagnosis of acute myocardial infarction was made in 133 of whom 100 received streptokinase. Dysrhythmia or shock was encountered in one-third of those given streptokinase and a quarter of the remainder. Reactions to streptokinase were recorded in 32 mainly hypotension or bradycardia alone or in combination. Forty-five per cent experienced either cardiac complications or drug reactions or both. During one month there were 57 admissions, 50 of whom arrived by ambulance. The mean delay between call out and arrival in the A&E department was 55 min. We concluded patients who are given thrombolytic therapy need close supervision and they should be nursed in a CCU or its equivalent.
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PMID:Coronary care follow-up study: acute care required immediately following thrombolytic therapy. 831 24

The 4 widely available thrombolytic agents, alteplase (recombinant tissue plasminogen activator, rt-PA), anisoylated plasminogen streptokinase activator complex (APSAC; anistreplase), streptokinase and urokinase have revolutionised the treatment of acute myocardial infarction and are also effective in treating pulmonary embolism and peripheral arterial thrombosis. Therapeutic efficacy of the agents appears to be similar. Choice of a thrombolytic agent depends more on patient characteristics, availability and familiarity with the drug, cost and differences in tolerability. While overall thrombolytic therapy is relatively safe, these 4 agents differ in their tolerability profiles. Streptokinase has the lowest cerebral haemorrhage rate, anistreplase an intermediate and alteplase the highest rate. The incidence of total stroke is also higher with alteplase and anistreplase than with streptokinase, translating to an actual difference in patient risk of 4 extra strokes per 1000 patients treated. Risk of major bleeding is dependent on predisposing factors and seems to be similar with each agent. The incidence of hypotension with alteplase (4.3% in ISIS-3) is less than with streptokinase or anistreplase (6.8 and 7.2%, respectively in ISIS-3). The incidence of major anaphylactic reactions with streptokinase and anistreplase is low (< 1%). Urokinase and alteplase may be preferred for readministration of thrombolytic therapy and anistreplase is the agent of choice where rapid completion of therapy is desirable. The various agents may have different tolerability profiles with different adjunctive therapies and further data are therefore required.
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PMID:Comparative tolerability profiles of thrombolytic agents. A review. 847 Nov 85

Streptokinase (SK), a bacterial product of pathogenic Streptococcus species, is now widely used as an effective therapy for the treatment of heart attacks. Because naturally occurring antibody to SK is ubiquitous, serious allergic reactions to SK therapy are common. To begin to identify regions of the molecule that are important for the antigenicity of SK we performed studies using a panel of 51 hybridomas producing anti-SK antibodies, recombinant SK fragments, and assays of SK activity. Antibodies generated from mice hyperimmunized with wild-type SK were shown to fall into six distinct complementation groups by competitive binding studies. Recombinant SK fragments were used to determine the peptide regions recognized by these complementation groups. Correlation of the effects of the mAb on SK function, with knowledge of their SK fragment-binding pattern, suggested regions of the SK molecule that are important for the construction and the catalytic function of the SK-plasminogen activator complex.
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PMID:A functional analysis of the antigenicity of streptokinase using monoclonal antibody mapping and recombinant streptokinase fragments. 848 42

Streptokinase, an extracellular protein produced by Streptococci, is capable of activating the human fibrinolytic zymogen plasminogen. The rate of amidolytic activity of the plasminogen-streptokinase complex is greatly diminished by micromolar concentrations of ATP and heparin oligosaccharides. In addition, the plasminogen activator activity of the plasminogen-streptokinase complex is also inhibited by these effectors. ATP and heparin oligosaccharides show structural similarity, suggesting that the inhibition is caused by binding of these molecules to a common newly formed binding pocket in streptokinase, which appears after interaction with plasminogen. Addition of the bivalent cations Ca2+ and Mg2+ reverses the inhibition caused by ATP and heparin. In the presence of ATP and bivalent cations, the complex between plasminogen and streptokinase develops an autophosphorylating activity whose target is the sequence LTSRPAHG in the 4.5 kDa streptokinase N-terminal peptide, which is an early autolysis peptide. This streptokinase N-terminal peptide, which is essential for streptokinase activating activity, may serve, once phosphorylated, in mechanisms related to the pathogenicity of Streptococci. These studies suggest a critical role for plasminogen in regulating the activity of the streptokinase molecule.
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PMID:ATP-regulated activity of the plasmin-streptokinase complex: a novel mechanism involving phosphorylation of streptokinase. 854 80

The focus of new research efforts to improve the morbidity and mortality associated with acute myocardial infarction (AMI) has turned to adjuvant agents that show promise of improving outcomes following coronary thrombolysis. We enrolled 162 patients with AMI in a randomized trial comparing front-loaded tissue-plasminogen activator (t-PA) plus weight-adjusted heparin with anisoylated plasminogen streptokinase activator complex (APSAC) without heparin as well as standard-dose (325 mg) and low-dose (81 mg) aspirin. The primary end point was an in-hospital morbidity profile; secondary end points were clinical and angiographic potency and hemorrhagic events. Selected sites performed an electrocardiographic substudy to determine the time to 50% ST-segment recovery and the time to steady state. Although the trial was terminated when the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries-I trial showed that t-PA had a significant mortality advantage over streptokinase, important trends were evident. Patients given t-PA and heparin were better anticoagulated (p = 0.001), yet AP-SAC-treated patients had more bleeding complications. The primary end point favored t-PA (25.4% vs 31.3%), and the secondary end points were similar in both groups. In the electrocardiographic substudy, the t-PA group achieved both 50% ST-segment recovery and steady-state recovery sooner than the APSAC group. Patients taking low-dose aspirin had lower in-hospital mortality and less recurrent ischemia but more strokes than the standard-dose aspirin group. Thus, this trial demonstrated trends favoring front-loaded t-PA with weight-adjusted heparin over APSAC without heparin in the treatment of AMI. The use of low-dose aspirin did not appear to impose a loss of protection from adverse events, nor did standard-dose aspirin increase serious bleeding.
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PMID:A randomized factorial trial of reperfusion strategies and aspirin dosing in acute myocardial infarction. The DUCCS-II Investigators. 862 29

Intraarterial thrombolysis is used increasingly for management of arterial and bypass graft occlusions. Current research has been directed at the indications for and methods of catheter-directed thrombolysis. Streptokinase, urokinase, and tissue plasminogen activator (t-PA) are the most commonly used agents. They are administered by a variety of techniques and in various doses involving intrathrombic infusions, thrombus lacing, high-dose bolus therapy, and pulse-spray lysis. The latter methods appear to produce thrombolysis within a few hours, so this chemical therapy has the potential to become the first-line management for all episodes of acute limb ischemia. The role of thrombolysis is to return patients to their prethrombotic or preembolic state, so the underlying condition can be treated by radiologic intervention, surgery, or anticoagulation. Intraarterial thrombolysis is indicated for occlusions of less than 2 weeks' duration where the limb is able to withstand a period of further ischemia. Older occlusions should be treated by surgery, reserving intraoperative lysis for specific situations.
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PMID:Lower limb intraarterial thrombolysis as an adjunct to the management of arterial and graft occlusions. 866 48

Currently several modes of reperfusion therapy for acute myocardial infarction are available. Streptokinase, accelerated alteplase and direct angioplasty are the most frequently used. These options are increasingly effective, but are also increasingly complex and costly. Since, unfortunately, physicians are often restricted by budget limitations, choices must be made in clinical practice to provide optimal therapy to individual patients. In order to guide such decision making, we developed a model to predict the expected benefit of therapy in terms of gain in life expectancy. Patients' life expectancy will decrease after infarction. Part of this loss can be prevented by early reperfusion therapy. The clinical benefit of therapy ranges from negligible gain in patients with small infarcts treated relatively late to an expected gain of more than 2 years in patients with extensive infarction treated within 3 h of onset of symptoms. The expected benefits are presented in a set of tables and depend on age, previous infarction, estimated infarct size, treatment delay and intracranial bleeding risk. With the help of these table, resources will be allocated in such a manner that patients who will benefit the most will receive the most effective therapy. Patients with similar expected treatment benefit will be offered the same mode of therapy. Future life years were discounted at 5% per year. The arbitrary thresholds currently applied for decision making at the Thoraxcenter are: no reperfusion therapy when the estimated gain in discounted life expectancy was < 1 month, streptokinase for 1-4 months and accelerated alteplase for a gain > or = 5 months. Direct angioplasty is recommended in patients with an estimated gain > or = 12 months, and in patients with an increased risk of intracranial bleeding. In this way, approximately 80% of our patients will be treated with thrombolytics (40% streptokinase and 40% accelerated alteplase), while in 10% direct angioplasty will be initiated. Patients with small infarcts presenting late will not receive reperfusion therapy. These threshold values have been chosen arbitrarily, and different thresholds may be selected in other centres. However, the developed model would guarantee that treatment decisions are made in a consistent manner, to provide optimal therapy for patients with evolving myocardial infarction, in spite of limited resources.
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PMID:Estimated gain in life expectancy. A simple tool to select optimal reperfusion treatment in individual patients with evolving myocardial infarction. 868 32

The era of coronary reperfusion in acute coronary care was made possible by the recognition that acute myocardial infarction is usually due to a ruptured atherosclerotic plaque with associated thrombosis. If the infarct artery becomes occluded, a typical electrocardiographic picture is produced and a wave-front of myocardial necrosis ensues. Reperfusion during the early postinfarction hours can halt this process and preserve myocardial function. Pooled analysis of data in almost 60,000 patients has shown that thrombolysis saves lives relative to no reperfusion therapy. Streptokinase has been the standard thrombolytic agent, but recent data from the GUSTO trial show that tissue plasminogen activator (t-PA) given in an accelerated dosing regimen saves one extra patient per hundred treated. The mechanism of benefit of t-PA is improved early and complete restoration of blood flow down the infarct artery. Economic analysis of the GUSTO data shows that t-PA is an "economically attractive" therapeutic technology with a cost-effectiveness ratio of approximately $33,000 per life-year added relative to streptokinase therapy. Because of the growth of managed care and other cost-containment forces, expensive new medical technologies will increasingly need to demonstrate that they produce extra medical benefits in appropriate measure for their extra costs.
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PMID:Clinical and economic lessons from studies of coronary thrombolysis. 877 Aug 50


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