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

The safety and efficacy of a new regimen of intravenous recombinant tissue-type plasminogen activator (rt-PA) potentially suitable for either pre- or in-hospital administration were assessed in 60 patients with acute myocardial infarction in an open label coronary angiographic study. The regimen consisted of a 20-mg bolus dose followed 30 min later by a delayed infusion of 80 mg over 2 h. This regimen was designed to facilitate prehospital administration of rt-PA. Infarct-related artery patency (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) was observed in 40 of 53 patients at 60 min (75.5%, 95% confidence intervals [CI] 61% to 84%) and in 55 of 60 patients at 90 min (91.7%, 95% CI 80% to 95%) after the rt-PA bolus. By 90 min the majority of patients (55%) exhibited TIMI grade 3 flow; infarct artery patency at 120 min was 84.9%. During hospitalization definite recurrent ischemia occurred in nine patients (15%); nonfatal recurrent infarction was noted in one (1.7%). Four patients (6.7%) experienced major bleeding, including one with intracranial bleeding. There were seven deaths (11.7%). Mortality was significantly influenced by the occurrence of cardiogenic shock, which was present in five patients at the time of enrollment. Blood fibrinogen levels were obtained before and during rt-PA infusion. At baseline and 30 and 150 min after the bolus dose, the mean fibrinogen level (+/- SD) was 284.83 +/- 77.39, 237.96 +/- 76.92 and 192.04 +/- 57.82 mg/dl, respectively. Compared with the baseline value, there was a significant (p less than 0.05) decrease in fibrinogen at both 30 and 150 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Safety and efficacy of a new regimen of intravenous recombinant tissue-type plasminogen activator potentially suitable for either prehospital or in-hospital administration. 196 Mar 29

In a randomised, controlled trial 2514 patients with suspected acute myocardial infarction received 100 mg intravenous alteplase (recombinant tissue plasminogen activator [rt-PA]) plus heparin within 5 h of onset of symptoms, and 2499 similar controls received placebo plus heparin. At 1 month the overall mortality rates were 7.2% and 9.8%, respectively, a relative reduction of 26% (95% confidence interval [CI] 11-39%). At 6 months the mortality rates were 10.4% (alteplase) and 13.1% (placebo), a relative reduction of 21% (95% Cl 8%-32%, p = 0.0026). 6-month mortality rates in patients with proven myocardial infarction were 12.6% and 17.1%, respectively (relative reduction 26%; 95% Cl 14-37%); this effect was similar for anterior (15.6% vs 21.2%) and inferior (7.7% vs 12.8%) myocardial infarction. 6-month mortality rates were lower in those treated with alteplase irrespective of other recognised cardiac risk factors. However, treatment with alteplase made no difference to subsequent cardiac events after one month (readmissions, reinfarctions, death) nor to treatment for angina or heart failure. Product limit estimates of one year mortality are 13.2% with alteplase and 15.1% with placebo. The corresponding figures for patients with an index diagnosis of myocardial infarction are 15.7% and 18.9%, a relative reduction of 16.9%.
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PMID:Effects of alteplase in acute myocardial infarction: 6-month results from the ASSET study. Anglo-Scandinavian Study of Early Thrombolysis. 197 42

A multicentre, randomised, open trial with a 2 x 2 factorial design was conducted to compare the benefits and risks of two thrombolytic agents, streptokinase (SK, 1.5 MU infused intravenously over 30-60 min) and alteplase (tPA, 100 mg infused intravenously over 3 h) in patients with acute myocardial infarction admitted to coronary care units within 6 h from onset of symptoms. The patients were also randomised to receive heparin (12,500 U subcutaneously twice daily until discharge from hospital, starting 12 h after beginning the tPA or SK infusion) or usual therapy. All patients without specific contraindications were given atenolol (5-10 mg iv) and aspirin (300-325 mg a day). The end-point of the study was the combined estimate of death plus severe left ventricular damage. 12,490 patients were randomised to four treatment groups (SK alone, SK plus heparin, tPA alone, tPA plus heparin). No specific differences between the two thrombolytic agents were detected as regards the combined end-point (tPA 23.1%; SK 22.5%; relative risk 1.04, 95% Cl 0.95-1.13), nor after the addition of heparin to the aspirin treatment (hep 22.7%, no hep 22.9%; RR 0.99, 95% Cl 0.91-1.08). The outcome of patients allocated to the four treatment groups was similar with respect to baseline risk factors such as age, Killip class, hours from onset of symptoms, and site and type of infarct. The rates of major in-hospital cardiac complications (reinfarction, post-infarction angina) were also similar. The incidence of major bleeds was significantly higher in SK and heparin treated patients (respectively, tPA 0.5%, SK 1.0%, RR 0.57, 95% Cl 0.38-0.85; hep 1.0%, no hep 0.6%, RR 1.64, 95% Cl 1.09-2.45), whereas the overall incidence of stroke was similar in all groups. SK and tPA appear equally effective and safe for use in routine conditions of care, in all infarct patients who have no contraindications, with or without post-thrombolytic heparin treatment. The 8.8% hospital mortality of the study population (compared with approximately 13% in the control cohort of the GISSI-1 trial) indicates the beneficial impact of the proven acute treatments for AMI.
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PMID:GISSI-2: a factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. 197 87

In a study with 2 x 2 factorial design, 20,891 patients with suspected acute myocardial infarction of less than 6 h duration (12,490 from the GISSI-2 trial and 8401 recruited elsewhere) were randomly allocated to alteplase (recombinant tissue plasminogen activator, tPA) or streptokinase (SK) and to subcutaneous heparin, beginning 12 h after the start of thrombolytic therapy or no heparin. The protocol recommended that, in the absence of specific contraindications, all patients should receive aspirin and intravenous beta-blockade as soon as possible. No significant differences in hospital mortality were found between tPA and SK (8.9% versus 8.5%) or between heparin and no heparin (8.5% versus 8.9%). The incidence of major cardiac complications was also very similar in the different groups. For non-cardiac complications significant differences between the treatment groups were observed: more strokes were reported with tPA than with SK (1.3% versus 1%) while more major bleeds occurred with SK than with tPA (0.6% versus 0.9%). Subcutaneous heparin was likewise associated with an excess of major bleeds (1.0% with heparin versus 0.5% without heparin) but did not affect the incidence of stroke or reinfarction.
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PMID:In-hospital mortality and clinical course of 20,891 patients with suspected acute myocardial infarction randomised between alteplase and streptokinase with or without heparin. The International Study Group. 197 65

Coronary thrombolysis is the treatment of choice for patients with acute Q-wave myocardial infarcts who have no contraindications to such therapy. However, the time required for thrombolysis and the possibility of reocclusion of the infarct-related artery remain problematic. Herein are described experimental animal studies and clinical evaluations in which attempts have been made to develop adjunctive therapies that, when coupled with available thrombolytic interventions, might shorten the time to thrombolysis and delay or prevent reocclusion. From the studies conducted to date, it is clear that a combined thromboxane synthesis inhibitor and receptor antagonist with a serotonin receptor antagonist and heparin shorten the time to thrombolysis and delay or prevent coronary artery reocclusion in experimental canine models with copper coil-induced coronary artery thrombi. A monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor coupled with tissue plasminogen activator (t-PA) and heparin also shortens the time to thrombolysis and delays or prevents reocclusion in experimental canine models. Thrombin inhibitors, including heparin and synthetic inhibitors, given with t-PA and aspirin, appear to shorten the time to thrombolysis and delay or prevent coronary artery reocclusion in experimental canine models. Aspirin coupled with intravenous streptokinase reduces mortality in patients with presumed acute myocardial infarction, and a combination of heparin and t-PA results in infarct-artery patency more frequently than t-PA without heparin. Data from these studies are encouraging with regard to the possibility of developing effective and relatively safe thrombolytic regimens that shorten the time to thrombolysis and delay or prevent coronary artery reocclusion.
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PMID:Role of new antiplatelet agents as adjunctive therapies in thrombolysis. 199 Jul 81

The rationale for considering heparin therapy as an adjunct to thrombolytic treatment for patients with acute myocardial infarction is to prevent rethrombosis after successful thrombolysis. The risk of reocclusion is high immediately after thrombolysis because blood flowing through the newly opened coronary artery is exposed to thrombin bound to fibrin in the residual thrombus. Clinical studies of patients with venous thrombosis and acute myocardial infarction indicate that there is a relation between the anticoagulant response to heparin and clinical efficacy and that the concept of a therapeutic heparin level is valid. Subcutaneous doses of approximately 15,000 U twice a day fail to provide an adequate anticoagulant response at 24 hours in the majority of patients, whereas intravenous administration of a bolus of 5,000 U followed by continuous infusion of 30,000 U per 24 hours produces an adequate anticoagulant response at 24 hours in approximately 80% of patients. Studies of patients with myocardial infarction who received streptokinase showed a significant beneficial effect on mortality when 12,500 U of heparin was administered subcutaneously 2 times per day. In contrast, the single largest study evaluating heparin 12,500 U administered subcutaneously 2 times per day as an adjunct to recombinant tissue-type plasminogen activator (rt-PA) treatment did not show a beneficial effect on mortality. However, studies using full-dose intravenous heparin therapy demonstrated that heparin improves patency after coronary thrombolysis with rt-PA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heparin as an adjunctive treatment after thrombolytic therapy for acute myocardial infarction. 199 Jul 83

Troponin T is a structurally bound protein found in striated muscle cells. We tested concentrations of its cardiac-specific isotype in peripheral venous blood samples serially drawn from 72 patients with confirmed myocardial infarction. Fifty-nine patients received thrombolytic treatment with intravenous streptokinase, urokinase, or recombinant tissue-type plasminogen activator; because of contraindications, the remaining 13 patients did not. Concentrations of troponin T in plasma, measured by an enzyme-linked immunosorbent assay, started increasing within a few hours after the onset of symptoms (median, 4 h; range, 1-10 h). The sensitivity of troponin T for detecting myocardial infarction was 100% from 10 to 120 h after the onset of symptoms; sensitivity on the seventh day after admission was 84%. Concentrations were increased for up to three weeks in some patients with late or high peak values. Successful reperfusion in Q-wave infarction obviously influences the release of troponin T into plasma, with all such cases showing peak values less than or equal to 26 h (median, 14 h) after the onset of symptoms. Troponin T concentrations in these patients returned to within the reference interval more rapidly than in nonreperfused subjects. In the 13 patients without fibrinolytic therapy, troponin T tended to peak approximately 48 h (median) after the onset of chest pain. Troponin T concentrations in patients for whom thrombolysis was unsuccessful resembled those in patients without fibrinolytic therapy. The specificity of the assay was 96% as tested in samples of 96 emergency-room patients. The reference interval (less than 0.5 micrograms/L) was established from samples of 100 healthy blood donors. Troponin T measurements are a specific and sensitive method for the early and late diagnosis of acute myocardial infarction and could, therefore, provide a new criterion in laboratory diagnosis of its occurrence.
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PMID:Cardiac troponin T in diagnosis of acute myocardial infarction. 159 99

Thrombolytic therapy has significantly reduced the morbidity and mortality that was once associated with acute myocardial infarction. Because of the substantial benefits associated with this therapy, investigation has intensified in search of the optimal agent or agents. Five agents are currently being investigated individually and in various combinations to determine which agent(s) will outperform the others in terms of reperfusion, patency, mortality reduction, and clinical events. Two of the agents, t-PA and scu-PA, are considered fibrin selective, whereas the other three, streptokinase, urokinase and APSAC are nonselective. Whether this distinction provides substantial benefit is still not known. All of the FDA-approved agents (streptokinase, t-PA, and APSAC) have demonstrated survival benefit and will continue to be administered in AMI patients. In addition, the 1990s begins a new era that includes broadened selection criteria for AMI patients as well as expanding cardiovascular indications for thrombolytic therapy. The challenge to nurses is to improve and implement nursing care practices at the same rapid pace set by the medical discipline. This includes astute assessment and observational skills necessary to prevent and detect potential complications associated with thrombolytic therapy. Rapidly changing medical techniques mandate ongoing nursing research, which is needed to determine the most effective interventions in reducing complications associated with thrombolytic therapy and in promoting positive adaptive behaviors in the AMI patient. Thrombolytic therapy is an intervention for the 1990s, and nursing care is essential in maintaining the beneficial effects of this dynamic therapy.
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PMID:Pharmacologic review of thrombolytic agents. 209 66

Two in vitro models of coronary thrombolysis in man, i.e. dislodgement of thrombi formed from non-anticoagulated human blood, either by (i) shear-stress or (ii) interaction of platelets with type I collagen fibre, were studied. Heparinization (1 U/ml) of blood prior to thrombus formation by (i) strongly inhibited spontaneous dislodgement (P less than 0.0001). Heparin (1 U/ml), when added with streptokinase (SK) or tissue-type plasminogen activator (rt-PA) prior to thrombus formation, considerably delayed thrombolysis. Furthermore, thrombolysis occurred much earlier when thrombi were perfused with SK or rt-PA in native than in heparinized blood. Heparin inhibited binding of 125I-rt-PA (17%, P less than 0.02) and plasminogen (88%, P less than 0.0005) to platelets activated by ADP in citrated platelet-rich plasma. We conclude that heparin interferes with the fibrinolytic system at the surface of activated platelets. Our findings suggest that heparin administration prior to thrombolytic therapy for acute myocardial infarction should be questioned.
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PMID:Heparin inhibits spontaneous thrombolysis and the thrombolytic effect of both streptokinase and tissue-type plasminogen activator. An in vitro study of the dislodgement of platelet-rich thrombi formed from native blood. 210 72

Three hundred fifty-two patients with suspected acute myocardial infarction (AMI) were randomized to placebo (175) or tissue-type plasminogen activator (rt-PA) (177). Patients were eligible if evaluated within 165 minutes from onset of chest pain and if age was less than 75 years. Electrocardiographic criteria were not required. A mobile coronary care unit with a cardiologist present was used to initiate treatment at home in 29% of the patients. Primary endpoints were infarct size (serum lactate dehydrogenase isoenzyme activity), left ventricular function (radioangiography) and exercise capacity at 30 days. AMI was diagnosed in 59% of all randomized patients. The incidence was similar in the 2 groups (placebo, 108, rt-PA, 101). Among all randomized patients, rt-PA was associated with significantly decreased infarct size and an increased ejection fraction. Among rt-PA-treated patients there were significantly fewer Q-wave infarctions. No difference in exercise capacity could be detected. No benefit was found in subgroups of patients without ST-segment elevation on the initial electrocardiogram. There were 18 (10.3%) and 11 (6.2%) deaths (p = 0.23) within 30 days in the placebo and rt-PA groups, respectively. Adverse reactions were similar in both groups with no excess of complications in the home-treated group. Very early treatment with rt-PA in patients with a strong suspicion of AMI and ST-segment elevation limits infarct size and improves left ventricular function. The infarct pattern is shifted from Q-wave to non-Q-wave infarcts by rt-PA. The study suggests that thrombolysis can be given before hospital admission without additional risk. Furthermore, electrocardiographic records are useful for selection of patients.
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PMID:Very early thrombolytic therapy in suspected acute myocardial infarction. The Thrombolysis Early in Acute Heart Attack Trial Study Group. 210 52


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