Alteplase : a reappraisal of its pharmacological properties and therapeutic use in acute myocardial infarction

Alteplase (recombinant tissue-type plasminogen activator) stimulates the fibrinolysis of blood clots by converting plasminogen to plasmin. The efficacy of intravenous alteplase in the early treatment of patients with acute myocardial infarction has been unequivocally proven, and recent results from...

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Veröffentlicht in:Drugs (New York, N.Y.) N.Y.), 1995-07, Vol.50 (1), p.102-136
Hauptverfasser: GILLIS, J. C, WAGSTAFF, A. J, GOA, K. L
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creator GILLIS, J. C
WAGSTAFF, A. J
GOA, K. L
description Alteplase (recombinant tissue-type plasminogen activator) stimulates the fibrinolysis of blood clots by converting plasminogen to plasmin. The efficacy of intravenous alteplase in the early treatment of patients with acute myocardial infarction has been unequivocally proven, and recent results from the GUSTO trial indicate a significant advantage in 30-day survival for alteplase in an accelerated dosage regimen (< or = 100mg infused over 90 minutes rather than 3 hours) over streptokinase. The advantage of the accelerated alteplase dosage regimen seems to be maintained for at least 1 year. The role of heparin as adjunctive therapy to thrombolysis remains to be fully defined but heparin administration appears to be more important in conjunction with alteplase than with streptokinase. Ideally, patients should receive alteplase as soon as possible after the onset of symptoms of acute myocardial infarction and, while therapy is most beneficial when administered early, survival is improved when the drug is administered up to 12 hours after symptom onset. The accelerated regimen of alteplase used in the GUSTO trial demonstrated a survival advantage in patients < or = 75 as well as those > 75 years of age which was at least as great as that seen with streptokinase. Similarly, alteplase reduces mortality in patients with both anterior and inferior infarctions; however, those with anterior wall infarctions show an improved outcome over those with inferior infarcts. On the basis of pharmacoeconomic analysis of GUSTO data, the accelerated alteplase regimen cost an estimated additional $US32,678 per year of life saved compared with a conventional streptokinase regimen. Cumulative 1-year costs were greater in patients who received the accelerated alteplase regimen but survival was significantly greater than in patients who received streptokinase. No difference in quality of life was evident in patients who received either treatment. The incidence of major haemorrhage associated with alteplase therapy appears to be similar to that seen with other fibrinolytic agents, increasing with increasing dose; however, the risk of stroke, particularly haemorrhagic stroke, is higher with alteplase than with streptokinase. Thus, alteplase has become firmly established as a first-line option in the management of acute myocardial infarction. On the basis of accumulated evidence, the greatest risk reduction with alteplase therapy may be in certain high risk groups, such as those with an
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C ; WAGSTAFF, A. J ; GOA, K. L</creator><creatorcontrib>GILLIS, J. C ; WAGSTAFF, A. J ; GOA, K. L</creatorcontrib><description>Alteplase (recombinant tissue-type plasminogen activator) stimulates the fibrinolysis of blood clots by converting plasminogen to plasmin. The efficacy of intravenous alteplase in the early treatment of patients with acute myocardial infarction has been unequivocally proven, and recent results from the GUSTO trial indicate a significant advantage in 30-day survival for alteplase in an accelerated dosage regimen (&lt; or = 100mg infused over 90 minutes rather than 3 hours) over streptokinase. The advantage of the accelerated alteplase dosage regimen seems to be maintained for at least 1 year. The role of heparin as adjunctive therapy to thrombolysis remains to be fully defined but heparin administration appears to be more important in conjunction with alteplase than with streptokinase. Ideally, patients should receive alteplase as soon as possible after the onset of symptoms of acute myocardial infarction and, while therapy is most beneficial when administered early, survival is improved when the drug is administered up to 12 hours after symptom onset. The accelerated regimen of alteplase used in the GUSTO trial demonstrated a survival advantage in patients &lt; or = 75 as well as those &gt; 75 years of age which was at least as great as that seen with streptokinase. Similarly, alteplase reduces mortality in patients with both anterior and inferior infarctions; however, those with anterior wall infarctions show an improved outcome over those with inferior infarcts. On the basis of pharmacoeconomic analysis of GUSTO data, the accelerated alteplase regimen cost an estimated additional $US32,678 per year of life saved compared with a conventional streptokinase regimen. 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C</creatorcontrib><creatorcontrib>WAGSTAFF, A. J</creatorcontrib><creatorcontrib>GOA, K. L</creatorcontrib><title>Alteplase : a reappraisal of its pharmacological properties and therapeutic use in acute myocardial infarction</title><title>Drugs (New York, N.Y.)</title><addtitle>Drugs</addtitle><description>Alteplase (recombinant tissue-type plasminogen activator) stimulates the fibrinolysis of blood clots by converting plasminogen to plasmin. The efficacy of intravenous alteplase in the early treatment of patients with acute myocardial infarction has been unequivocally proven, and recent results from the GUSTO trial indicate a significant advantage in 30-day survival for alteplase in an accelerated dosage regimen (&lt; or = 100mg infused over 90 minutes rather than 3 hours) over streptokinase. The advantage of the accelerated alteplase dosage regimen seems to be maintained for at least 1 year. 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On the basis of pharmacoeconomic analysis of GUSTO data, the accelerated alteplase regimen cost an estimated additional $US32,678 per year of life saved compared with a conventional streptokinase regimen. Cumulative 1-year costs were greater in patients who received the accelerated alteplase regimen but survival was significantly greater than in patients who received streptokinase. No difference in quality of life was evident in patients who received either treatment. The incidence of major haemorrhage associated with alteplase therapy appears to be similar to that seen with other fibrinolytic agents, increasing with increasing dose; however, the risk of stroke, particularly haemorrhagic stroke, is higher with alteplase than with streptokinase. Thus, alteplase has become firmly established as a first-line option in the management of acute myocardial infarction. 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L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c339t-b0dfc8b135cf09b3524e6503879cc460d9727238840517692de273600574c35f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aging - metabolism</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Cost-Benefit Analysis</topic><topic>Drug Administration Schedule</topic><topic>Drug Evaluation</topic><topic>Drug Therapy, Combination</topic><topic>Fibrinolytic Agents - pharmacokinetics</topic><topic>Fibrinolytic Agents - pharmacology</topic><topic>Fibrinolytic Agents - therapeutic use</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Myocardial Infarction - drug therapy</topic><topic>Myocardial Infarction - mortality</topic><topic>Pharmacology. 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L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alteplase : a reappraisal of its pharmacological properties and therapeutic use in acute myocardial infarction</atitle><jtitle>Drugs (New York, N.Y.)</jtitle><addtitle>Drugs</addtitle><date>1995-07-01</date><risdate>1995</risdate><volume>50</volume><issue>1</issue><spage>102</spage><epage>136</epage><pages>102-136</pages><issn>0012-6667</issn><eissn>1179-1950</eissn><coden>DRUGAY</coden><abstract>Alteplase (recombinant tissue-type plasminogen activator) stimulates the fibrinolysis of blood clots by converting plasminogen to plasmin. The efficacy of intravenous alteplase in the early treatment of patients with acute myocardial infarction has been unequivocally proven, and recent results from the GUSTO trial indicate a significant advantage in 30-day survival for alteplase in an accelerated dosage regimen (&lt; or = 100mg infused over 90 minutes rather than 3 hours) over streptokinase. The advantage of the accelerated alteplase dosage regimen seems to be maintained for at least 1 year. The role of heparin as adjunctive therapy to thrombolysis remains to be fully defined but heparin administration appears to be more important in conjunction with alteplase than with streptokinase. Ideally, patients should receive alteplase as soon as possible after the onset of symptoms of acute myocardial infarction and, while therapy is most beneficial when administered early, survival is improved when the drug is administered up to 12 hours after symptom onset. The accelerated regimen of alteplase used in the GUSTO trial demonstrated a survival advantage in patients &lt; or = 75 as well as those &gt; 75 years of age which was at least as great as that seen with streptokinase. Similarly, alteplase reduces mortality in patients with both anterior and inferior infarctions; however, those with anterior wall infarctions show an improved outcome over those with inferior infarcts. On the basis of pharmacoeconomic analysis of GUSTO data, the accelerated alteplase regimen cost an estimated additional $US32,678 per year of life saved compared with a conventional streptokinase regimen. Cumulative 1-year costs were greater in patients who received the accelerated alteplase regimen but survival was significantly greater than in patients who received streptokinase. No difference in quality of life was evident in patients who received either treatment. The incidence of major haemorrhage associated with alteplase therapy appears to be similar to that seen with other fibrinolytic agents, increasing with increasing dose; however, the risk of stroke, particularly haemorrhagic stroke, is higher with alteplase than with streptokinase. Thus, alteplase has become firmly established as a first-line option in the management of acute myocardial infarction. On the basis of accumulated evidence, the greatest risk reduction with alteplase therapy may be in certain high risk groups, such as those with anterior infarcts, selected elderly patients and those who present late after symptom onset.</abstract><cop>Auckland</cop><pub>Adis International</pub><pmid>7588083</pmid><doi>10.2165/00003495-199550010-00008</doi><tpages>35</tpages></addata></record>
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subjects Aged
Aged, 80 and over
Aging - metabolism
Biological and medical sciences
Blood. Blood coagulation. Reticuloendothelial system
Cost-Benefit Analysis
Drug Administration Schedule
Drug Evaluation
Drug Therapy, Combination
Fibrinolytic Agents - pharmacokinetics
Fibrinolytic Agents - pharmacology
Fibrinolytic Agents - therapeutic use
Humans
Medical sciences
Myocardial Infarction - drug therapy
Myocardial Infarction - mortality
Pharmacology. Drug treatments
Plasminogen Activators - pharmacokinetics
Plasminogen Activators - pharmacology
Plasminogen Activators - therapeutic use
Thrombosis - drug therapy
Tissue Plasminogen Activator - adverse effects
Tissue Plasminogen Activator - pharmacokinetics
Tissue Plasminogen Activator - pharmacology
Tissue Plasminogen Activator - therapeutic use
Treatment Outcome
Ventricular Function, Left - drug effects
title Alteplase : a reappraisal of its pharmacological properties and therapeutic use in acute myocardial infarction
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