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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptokinase and alteplase are established therapies in acute myocardial infarction. Reteplase is a new thrombolytic agent that can be given as a double bolus. This trial was designed to determine whether the effect of reteplase on survival was at least equivalent (within 1% of fatality rate) to that of a standard streptokinase regimen. Patients from 208 centres in nine countries (n = 6010) with symptoms and electrocardiographic criteria consistent with acute myocardial infarction were randomised to receive double-blind either streptokinase 1.5 MU intravenously over 60 min or reteplase two boluses of 10 MU given 30 min apart. Treatment could be started up to 12 h from onset of symptoms. All patients received intravenous heparin for at least 24 h. The primary endpoint was 35-day outcome. There were 270 deaths (9.02%) in the reteplase and 285 deaths (9.53%) in the streptokinase group, a non-significant difference (95% CI -1.98% to 0.96%). Among patients who received treatment (98.8%) there were 263 deaths (8.90%) in the reteplase compared with 279 deaths (9.43%) in the streptokinase group (a difference of -0.53%). Because the upper limit of the 90% CI for this difference is 0.71%, this result shows that reteplase is at least as effective as streptokinase. In-hospital stroke rates were 1.23% for reteplase and 1.00% for streptokinase. Bleeding events were similar in the two treatment groups (0.7% reteplase, 1.0% streptokinase). The incidence of recurrent myocardial infarction was similar, but there were significantly fewer cases of atrial fibrillation, asystole, cardiac shock, heart failure, and hypotension in the reteplase group. We conclude that reteplase is an effective drug in the treatment of acute myocardial infarction. It is clinically safe, its administration is simple, and it will be a useful addition to the range of thrombolytic agents available.
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PMID:Randomised, double-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction (INJECT): trial to investigate equivalence. International Joint Efficacy Comparison of Thrombolytics. 1111 34

Thrombolytic therapy remains a mainstay for the treatment of patients with acute myocardial infarction. This therapy has been the subject of intense investigation and multiple studies as well as substantial controversy. Controversial issues include, among others, the specific drug, need for heparin, the relation between time to treatment and outcome and risk/benefit considerations. The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial of 41,021 patients addressed many of these issues. The results of the main trial were conclusive--treatment with accelerated tissue-type plasminogen activator (t-PA) resulted in a decreased mortality rate with a 15% reduction (95% confidence interval 5.9 to 21.3) compared with the two streptokinase monotherapy strategies (p = 0.001). Virtually all subgroup analyses, including age, nonanterior infarction location, patients undergoing bypass graft surgery and hypertensive patients, showed remarkable consistency with improved outcome with accelerated t-PA. This reduction in all-cause mortality with accelerated t-PA was associated with a small (absolute 0.2%) but significant increase in hemorrhagic stroke (p = 0.03). A combined end point of death or disabling stroke, or both, was still decreased in the accelerated t-PA group compared with the streptokinase group (p = 0.006). The angiographic substudy evaluated the mechanism of improved outcome and documented that reperfusion therapy works by restoring Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow early, improving left ventricular function and improving mortality. The most favorable outcome seen with t-PA was related to the finding that it resulted in improved TIMI grade 3 flow compared with that for streptokinase.
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PMID:Lessons we have learned from the GUSTO trial. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries. 777 8

Streptokinase has been administered to many thousands of elderly patients with acute myocardial infarction. Results of large, randomised trials provide convincing evidence that intravenous streptokinase confers a distinct survival benefit in this population subgroup following myocardial infarction. The placebo-controlled ISIS-2 study demonstrated a 5-week absolute mortality reduction of 38 per 1000 patients aged 60 to 69 years administered streptokinase, compared with only 16 per 1000 for patients aged less than 60 years. Combining streptokinase with aspirin further reduces mortality, as shown by a 5-week absolute mortality reduction of 70 per 1000 patients aged 60 to 69 years administered this regimen in the ISIS-2 trial. While ideally patients should receive streptokinase as soon as possible after symptom onset, late benefit has been observed in patients presenting up to 12 hours after pain onset, as is often the case with the elderly. Indeed, in patients treated > 6 hours after infarct in the GUSTO trial, streptokinase produced lower mortality results than accelerated recombinant tissue plasminogen activator (rt-PA). However, in contrast to the similar effects of streptokinase and conventionally administered rt-PA on overall survival demonstrated in previous large trials, the GUSTO study showed a lower mortality rate for accelerated rt-PA than for streptokinase in the elderly and in the total patient population. The most frequent adverse effects associated with streptokinase therapy are haemorrhagic complications, with an incidence of 0.4% for major bleeding (requiring transfusion) and 3.6% for minor bleeding among the total population in the GISSI-1 and ISIS-2 trials. An excess of stroke, particularly haemorrhagic stroke, occurring with rt-PA in GUSTO and other major mortality trials affirms the use of streptokinase as a suitable option in the elderly who are at increased risk of this complication. Significantly reduced values of end-systolic volume and regional wall motion index have been observed in elderly patients following streptokinase therapy. Overall, streptokinase and rt-PA seem to cause similar improvements in left ventricular function in this age group. Patency of occluded coronary arteries appears to be achieved in a high percentage of elderly patients following streptokinase therapy, based on a small sample. Thus, in view of the extensive clinical experience that now exists, intravenous streptokinase represents an appropriate alternative in elderly patients with acute myocardial infarction, and may be considered a first-line therapy in selected individuals, such as those with multiple risk factors for stroke or who present later than 6 hours after infarct.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Streptokinase. A review of its pharmacology and therapeutic efficacy in acute myocardial infarction in older patients. 813 Mar 84

Thrombolytic therapy has been proposed in the treatment of cerebrovascular occlusive disease. Early clinical experiences with Urokinase and Streptokinase raised concern about the risk of hemorrhagic complications. More recently, tissue plasminogen activator (tPA) has been evaluated experimentally with promising results. Its clinical utilization has been recently initiated. A review of experimental and clinical data on thrombolysis in cerebral ischemia is presented. TPA treatment produced recanalization and clinical improvement in several patients. The rate of intracranial hemorrhagic complications is similar to the incidence of spontaneous hemorrhagic conversion of ischemic infarction. Nevertheless, large placebo-controlled clinical trials are necessary to further define the efficacy and the optimal modality of administration of tPA in thromboembolic stroke.
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PMID:Thrombolysis in cerebral ischemia. A review of clinical and experimental data. 830 72

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

Utilization of angiography after acute myocardial infarction (AMI) treated with thrombolytics has been shown in large clinical trials to be related primarily to the availability of the procedure and not individual clinical circumstances. This study evaluated the regional influence of overall population cardiovascular mortality on utilization of angiography in the United States participants of the Global Utilization of Streptokinase and t-PA for Occluded Arteries (GUSTO-1) trial. Published summary statistics from GUSTO-1 and U.S. Census Bureau 1991 data were evaluated using simple and multiple linear regression with analysis for outliers. Region predictor variables (age adjusted) included mean total cardiovascular deaths/100,000/year (ICD/9 codes 390 to 459), mean coronary artery disease deaths/ 100,000/year (ICD/9 codes 410 to 414), and mean stroke deaths/100,000/year (ICD/9 codes 430 to 438), with the major outcome being regional proportion of GUSTO-1 patients undergoing angiography during the hospital stay after treatment with thrombolysis. All 3 cardiovascular death rates varied significantly by region (p < 0.00002) with no significant difference in GUSTO-1 mortality by region (p = 0.25). Simple linear regression analysis revealed associations between regional death rates and angiography use (r = 0.60, p = 0.12; r = 0.39, p = 0.33; r = 0.81, and p = 0.015). Multiple stepwise linear regression analysis found regional death rate due to stroke as the strongest predictor of angiography use with 65.86% of the variation explained by the model. New England was found to be a consistent outlier with reduced angiography use because of its background regional disease burden. This study confirms regional bias in the use of angiography in GUSTO-1. This form of operator bias appears to be due to more aggressive practice patterns in regions, except New England, where the overall cardiovascular disease burden is greater in terms of lives lost per 100,000 per year.
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PMID:Influence of regional cardiovascular mortality on the use of angiography after acute myocardial infarction. 906 11

Approximately 80 to 90% of cerebral ischaemic events that occur within 24 hours of symptom onset are due to atherothrombotic or thromboembolic occlusions. This forms the rationale for the use of thrombolytic agents in patients with acute ischaemic stroke. Early studies determined that recanalisation occurred in approximately 21 to 72% of patients with occluded cerebral arteries after intra-arterial or intravenous administration of streptokinase, urokinase, alteplase (recombinant tissue-type plasminogen activator; rt-PA) or duteplase (a 2-chain rt-PA). Initial reports suggested that frequencies of haemorrhagic transformation and parenchymatous haematoma in the carotid territory were similar whether patients with middle cerebral artery stroke received thrombolysis via intra-arterial or intravenous administration. The Multicentre Acute Stroke Trial-Europe (MAST-E), the Australia Streptokinase (ASK), and the Multicentre Acute Stroke Trial-Italy (MAST-I) trials, which evaluated intravenous streptokinase 1.5 x 10(6) IU in patients with acute ischaemic stroke, were terminated prematurely because of excessive early mortality and symptomatic intracranial haemorrhage in streptokinase recipients compared with those treated with placebo. However, those studies had not been preceded by dose-ranging trials. Intravenous administration of alteplase 0.9 mg/kg within 3 hours [National Institute of Neurological Disorders and Stroke (NINDS) trial], or 1.1 mg/kg within 6 hours [European Cooperative Acute Stroke Study (ECASS)], of symptom onset in patients with acute ischaemic stroke resulted in an absolute 11 to 13% treatment-associated improvement in clinical measurement scales; such as the modified Rankin scale and Barthel index, compared with placebo recipients. In the ECASS trial, those results were limited to a 'target population' restricted to those who satisfied all entry criteria. In both trials, the frequency of symptomatic haemorrhage was greater in patients treated with alteplase than with placebo and reinforced the importance of careful patient selection. Strict patient selection remains central to the success of this approach.
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PMID:Thrombolytic therapy in the treatment of stroke. 936 Aug 56

The use of outcome markers other than mortality reduction alone for evaluating thrombolytic agents in patients with acute myocardial infarction (AMI) is discussed. Mortality has been a primary endpoint in clinical trials evaluating thrombolytic agents for treatment of AMI. However, differences in mortality rates among thrombolytics are 1% or less and require tens of thousands of patients to detect. Broadening the endpoints studied will allow for more extensive data collection and more comprehensive cost-effectiveness analysis, enabling clinicians to make better decisions. The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial measured not only mortality but issues related to the patency of the infarct-related artery and complications. Other potentially important outcome markers after AMI are left ventricular function; markers of reperfusion, such as early resolution of ST-segment elevation; and resolution of chest pain. Available long-term data show that the mortality benefit from alteplase is sustained over time and is correlated with enzymatically determined infarct size, left ventricular function, the number of diseased vessels, and Thrombolysis in Myocardial Infarction flow grade at the time of discharge from the hospital. Clinicians must also consider risk factors for stroke. Outcome measures other than mortality alone may help in determining which thrombolytic agent is most effective clinically and in financial decision-making without requiring large, expensive trials.
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PMID:Clinical trials in thrombolytic therapy, Part 1: Outcome markers that go beyond mortality reduction. 939 34

The Australian Streptokinase Trial was a randomized, double-blind, placebo-controlled trial, in which streptokinase (SK, 1.5 million IU I.V.) was given within 4 hours of stroke onset. In a subset of 37 patients, 99mTc-labeled D,L-hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) and/or transcranial Doppler (TCD) studies were performed before and after therapy to test the hypothesis that SK may improve the hemodynamic measures of reperfusion/recanalization rates (TCD parameter) within 24 hours. Eighteen patients received SK and 19 placebo. Baseline characteristics were similar in both groups, and there were no differences in clinical outcomes assessed at 3 months after stroke. Although there was no increase in the group mean perfusion defect or volume on SPECT after thrombolytic therapy, a larger number of patients demonstrating the combined end point of reperfusion or recanalization was seen in the SK group (13/14, 93%) than in the placebo group (7/14, 50%; p = 0.01). Although SK given within 4 hours of acute ischemic stroke appears to improve arterial patency/tissue reperfusion, this effect is neither early nor extensive enough to influence overall clinical outcome.
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PMID:Streptokinase in acute stroke: effect on reperfusion and recanalization. Australian Streptokinase Trial Study Group. 952 Dec 47

The effective treatment of acute ischemic stroke remains an important goal of modern medicine and substantive advances are occurring. Recently, thrombolytic therapy with tissue-type plasminogen activator was approved for selected patients with acute ischemic stroke when therapy is started within 3 hours of onset. Streptokinase therapy for acute ischemic stroke has not been shown to be effective and is associated with an increased risk of hemorrhage, although it was not evaluated as early after stroke onset as tissue-type plasminogen activator. Various types of neuroprotective interventions are effective in animal models, but none has yet been proven effective in patients. In the future, combinations of thrombolytic and neuroprotective drugs may be used to attempt maximum rates of recovery after acute ischemic stroke. For combination therapy to achieve its maximum potential, patients with acute ischemic stroke will have to be carefully selected and treated.
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PMID:Further evolution toward effective therapy for acute ischemic stroke. 956 13


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