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Luc Pierard - One of the best experts on this subject based on the ideXlab platform.
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evaluation of a weight adjusted single bolus plasminogen activator in patients with myocardial infarction a double blind randomized angiographic trial of Lanoteplase versus alteplase
Circulation, 1998Co-Authors: Den P Heijer, Ettore Ambrosioni, F Vermeer, Z Sadowski, Jose Lopezsendon, R Von Essen, P Beaufils, Udho Thadani, Jennifer Adgey, Luc PierardAbstract:Background —Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. Methods and Results —InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted Lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of Lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P <0.001). Similar results were observed at 90 minutes (26.1% to 57.1%, P <0.001). At 90 minutes, coronary patency (TIMI 2 or 3) increased across the dose range up to 83% of subjects at 120 kU/kg Lanoteplase compared with 71.4% with alteplase. Thus, at this dose, Lanoteplase was superior to alteplase in restoring coronary patency (difference, 12%; 95% CI, 1% to 23%). The early safety experience in this study suggests that Lanoteplase was well tolerated at all doses with safety comparable to that of alteplase. Conclusions —Lanoteplase, a single-bolus, weight-adjusted agent, increased coronary patency at 60 and 90 minutes in a dose-dependent fashion. Coronary patency at 90 minutes was achieved more frequently with 120 kU/kg Lanoteplase than alteplase. In this study, safety with Lanoteplase and alteplase was comparable. InTIME-II, a worldwide mortality trial, will evaluate efficacy and safety with this promising new agent.
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Evaluation of a Weight-Adjusted Single-Bolus Plasminogen Activator in Patients With Myocardial Infarction A Double-Blind, Randomized Angiographic Trial of Lanoteplase Versus Alteplase
Circulation, 1998Co-Authors: P. Den Heijer, Ettore Ambrosioni, F Vermeer, Z Sadowski, R Von Essen, P Beaufils, Udho Thadani, Jennifer Adgey, Jl Lopez-sendon, Luc PierardAbstract:Background —Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. Methods and Results —InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted Lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of Lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P
Udho Thadani - One of the best experts on this subject based on the ideXlab platform.
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Comparison of Pharmacokinetics of Lanoteplase and Alteplase During Acute Myocardial Infarction
Clinical Pharmacokinetics, 2002Co-Authors: John B. Kostis, Udho Thadani, Ralph H. Raymond, Randy C. Dockens, Vasnath Bethala, Carl Pepine, Wayne Leimbach, Nimish Vachharajani, Bruce C. Stouffer, Lee K. TayAbstract:Objective Lanoteplase is a rationally designed variant of tissue plasminogen activator. The aim of this study was to examine the pharmacokinetics and functional activity of a single intravenous bolus dose of Lanoteplase with those of a bolus plus two-step infusion of alteplase. Design Seven-centre substudy of the InTIME-I angiographic trial in patients presenting within 6 hours of onset of suspected acute myocardial infarction. Patients and Participants A total of 31 patients (28 males, 3 females) enrolled in this substudy [mean age 59 (range 26 to 76) years]. Methods Twenty-three patients randomised to Lanoteplase received single bolus doses of 15 kU/kg (n = 5), 30 kU/kg (n = 3), 60 kU/kg (n = 9), or 120 kU/kg (n = 6). Eight patients received alteplase ≤-100mg as a bolus followed by a two-stage 90 min infusion. Blood samples were analysed for antigen concentration and plasminogen activator (PA) activity. Results The distribution plasma half-life of approximately 35 min for Lanoteplase was at least five times longer than that of alteplase. Lanoteplase plasma clearance averaged 3 L/h (50 ml/min), whereas the mean plasma clearance of approximately 24 L/h (400 ml/min) for alteplase approaches hepatic blood flow following acute myocardial infarction. PA activity after Lanoteplase 120 kU/kg remained for 6 hours, compared with less than 4 hours after alteplase 100mg. Conclusions The longer antigen and activity half-lives, slower clearance and less complicated administration of Lanoteplase compared with alteplase suggest that it may offer advantages for use as a single intravenous bolus to achieve reperfusion after myocardial infarction.
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Comparison of pharmacokinetics of Lanoteplase and alteplase during acute myocardial infarction.
Clinical pharmacokinetics, 2002Co-Authors: John B. Kostis, Udho Thadani, Nimish N. Vachharajani, Ralph H. Raymond, Bruce Stouffer, Randy C. Dockens, Vasnath Bethala, Carl Pepine, Wayne Leimbach, Lee K. TayAbstract:Objective Lanoteplase is a rationally designed variant of tissue plasminogen activator. The aim of this study was to examine the pharmacokinetics and functional activity of a single intravenous bolus dose of Lanoteplase with those of a bolus plus two-step infusion of alteplase.
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evaluation of a weight adjusted single bolus plasminogen activator in patients with myocardial infarction a double blind randomized angiographic trial of Lanoteplase versus alteplase
Circulation, 1998Co-Authors: Den P Heijer, Ettore Ambrosioni, F Vermeer, Z Sadowski, Jose Lopezsendon, R Von Essen, P Beaufils, Udho Thadani, Jennifer Adgey, Luc PierardAbstract:Background —Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. Methods and Results —InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted Lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of Lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P <0.001). Similar results were observed at 90 minutes (26.1% to 57.1%, P <0.001). At 90 minutes, coronary patency (TIMI 2 or 3) increased across the dose range up to 83% of subjects at 120 kU/kg Lanoteplase compared with 71.4% with alteplase. Thus, at this dose, Lanoteplase was superior to alteplase in restoring coronary patency (difference, 12%; 95% CI, 1% to 23%). The early safety experience in this study suggests that Lanoteplase was well tolerated at all doses with safety comparable to that of alteplase. Conclusions —Lanoteplase, a single-bolus, weight-adjusted agent, increased coronary patency at 60 and 90 minutes in a dose-dependent fashion. Coronary patency at 90 minutes was achieved more frequently with 120 kU/kg Lanoteplase than alteplase. In this study, safety with Lanoteplase and alteplase was comparable. InTIME-II, a worldwide mortality trial, will evaluate efficacy and safety with this promising new agent.
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Evaluation of a Weight-Adjusted Single-Bolus Plasminogen Activator in Patients With Myocardial Infarction A Double-Blind, Randomized Angiographic Trial of Lanoteplase Versus Alteplase
Circulation, 1998Co-Authors: P. Den Heijer, Ettore Ambrosioni, F Vermeer, Z Sadowski, R Von Essen, P Beaufils, Udho Thadani, Jennifer Adgey, Jl Lopez-sendon, Luc PierardAbstract:Background —Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. Methods and Results —InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted Lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of Lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P
Elliott M. Antman - One of the best experts on this subject based on the ideXlab platform.
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Availability of on-site catheterization and clinical outcomes in patients receiving fibrinolysis for ST-elevation myocardial infarction
European heart journal, 2001Co-Authors: Joan Llevadot, Robert P. Giugliano, Elliott M. Antman, Robert G. Wilcox, Enrique P. Gurfinkel, Andrew Charlesworth, S.l Thompson, Timothy D. Henry, Carolyn H. Mccabe, Jose C. NicolauAbstract:Aims To compare management and clinical outcomes in hospitals stratified by the availability of on-site catheterization in InTIME-II, a multicentre trial comparing alteplase with Lanoteplase for acute myocardial infarction. Methods and Results We studied 15–078 patients enrolled in 35 countries and 855 hospitals. Thirty-one percent of hospitals had 24-h, 25% day-only, and 44% no on-site catheterization facilities. Rates of cardiac angiography (57%, 38%, 26%) and revascularization (37%, 21%, 17%) were higher in hospitals with increasing access to on-site facilities ) Conclusions There is a marked variation in procedure use by the availability of on-site catheterization with no major differences in patient outcomes. There is a need for additional randomized trials in the current era to address both the appropriate selection of patients and timing of invasive procedures in ST-elevation acute myocardial infarction.
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Geographic variation in patient and hospital characteristics, management, and clinical outcomes in ST-elevation myocardial infarction treated with fibrinolysis. Results from InTIME-II.
European heart journal, 2001Co-Authors: Robert P. Giugliano, Joan Llevadot, Robert G. Wilcox, Enrique P. Gurfinkel, Colm Mccabe, Andrew Charlesworth, S.l Thompson, Elliott M. AntmanAbstract:Aims We examined the geographic variations in InTIME-II, a randomized double-blind trial comparing alteplase with Lanoteplase for myocardial infarction. Methods and Results We compared baseline characteristics, management, and outcomes in four regions (Western Europe, Eastern Europe, North America, and Latin America) and in countries with historically different management approaches (Germany vs the U.K., the U.S. vs Canada). Thirty-day mortality in Western Europe, Eastern Europe, North America and Latin America was 6.7%, 7.3%, 5.7%, 10.1%, P
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Bolus fibrinolytic therapy in acute myocardial infarction.
JAMA, 2001Co-Authors: Joan Llevadot, Robert P. Giugliano, Elliott M. AntmanAbstract:ContextNew bolus fibrinolytics derived from the human tissue-type plasminogen activator (tPA) have emerged as a means of dissolution of occlusive thrombosis associated with acute myocardial infarction.ObjectiveTo review the new bolus fibrinolytic drugs derived from tPA: reteplase, Lanoteplase, and tenecteplase.Data SourcesThe MEDLINE, EMBASE, and Current Contents databases were searched for articles from 1983 to 2001, using the index terms pharmacokinetics, pharmacodynamics, plasminogen activator, reteplase, Lanoteplase, and tenecteplase. Additional data sources included bibliographies of articles identified on MEDLINE, EMBASE, and Current Content, inquiry of experts and pharmaceutical companies, and preliminary data presented at recent national and international cardiology conferences.Study SelectionWe selected for review studies that evaluated the pharmacokinetics and pharmacodynamics of reteplase, Lanoteplase, and tenecteplase, and assessed the effects of these bolus fibrinolytic drugs on the angiographic and immediate and long-term outcomes of patients. Of 138 articles identified, 38 were analyzed.Data ExtractionData quality was determined by publication in the peer-reviewed literature or presentation at an official cardiology society–sponsored meeting.Data SynthesisTenecteplase and reteplase are comparable with accelerated infusion recombinant tPA in terms of efficacy and safety but more convenient because they are administered by bolus injection. Lanoteplase and heparin bolus plus infusion is as effective as tPA with regard to mortality, but the rate of intracranial hemorrhage is significantly higher.ConclusionGiven the ease of administration and the similar outcomes compared with accelerated infusion recombinant tPA, it is likely that a key component of contemporary reperfusion will include a bolus fibrinolytic.
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Lower-dose heparin with fibrinolysis is associated with lower rates of intracranial hemorrhage
American heart journal, 2001Co-Authors: Robert P. Giugliano, Christopher P. Cannon, Elliott M. Antman, Robert G. Wilcox, Carolyn H. Mccabe, Frans Van De Werf, Eugene BraunwaldAbstract:Abstract Background The optimal heparin dose as an adjunct to fibrinolysis and its role in causing intracranial hemorrhage (ICH) is unclear. Methods We reviewed the heparin regimens and rates of ICH in 3 sets of recent fibrinolytic trials: (1) studies with accelerated recombinant tissue plasminogen activator (TPA, alteplase) plus intravenous heparin, in which the heparin regimen was changed during the course of the trial; (2) phase III trials with accelerated TPA plus intravenous heparin; and (3) trials of new single-bolus fibrinolytic agents. Results Lower rates of ICH were observed among studies of accelerated TPA that reduced the heparin dose mid-trial (TIMI 9A → 9B: 1.87% → 1.07%, GUSTO-IIa → IIb: 0.92% → 0.71%, TIMI 10B: 2.80% → 1.16%). Rates of ICH with accelerated TPA gradually increased from GUSTO-I (0.72%) in 1990 to 1993 to ASSENT-2 (0.94%) in 1997 to 1998. However, this trend was reversed in InTIME-II, which used the lowest heparin dose and most aggressive activated partial thromboplastin time monitoring and observed an ICH rate of 0.64% with accelerated TPA. Lower ICH rates were also observed when the heparin dose was reduced with single-bolus tenecteplase (TNK-TPA) and Lanoteplase. Conclusions Nonrandomized comparisons with accelerated TPA suggest that lower doses of intravenous heparin are associated with lower rates of ICH. This observation also appears to apply to single-bolus TNK-TPA and novel plasminogen activator. A lower-dose, weight–adjusted heparin regimen (60 U/kg bolus; maximum, 4000 U; 12 U/kg per hour infusion; maximum, 1000 U/h) with earlier monitoring of activated partial thromboplastin time is currently recommended in the revised American College of Cardiology/American Heart Association myocardial infarction guidelines and should be used in clinical practice. (Am Heart J 2001;141:742-50.)
Ettore Ambrosioni - One of the best experts on this subject based on the ideXlab platform.
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Intravenous NPA for the treatment of infarcting myocardium early: InTIME-II, a double-blind comparison on of single-bolus Lanoteplase vs accelerated alteplase for the treatment of patients with acute myocardial infarction
European Heart Journal, 2000Co-Authors: Eugene Braunwald, K. L. Neuhaus, E. Antman, P. Chew, Ettore Ambrosioni, R. Wilcox, A Skene, Eduard Apetrei, J. Anderson, Imre BataAbstract:Aims to compare the efficacy and safety of Lanoteplase, a single-bolus thrombolytic drug derived from alteplase tissue plasminogen activator, with the established accelerated alteplase regimen in patients presenting within 6 h of onset of ST elevation acute myocardial infarction. Methods and Results 15 078 patients were recruited from 855 hospitals worldwide and randomized in a 2:1 ratio to receive either Lanoteplase 120 KU. kg -1 as a single intravenous bolus, or up to 100 mg accelerated alteplase given over 90 min. The primary end-point was all-cause mortality at 30 days and the hypothesis was that the two treatments would be equivalent. By 30 days, 6.61% of alteplase-treated patients and 6.75% Lanoteplase-treated patients had died (relative risk 1.02). Total stroke occurred in 1.53% alteplase- and 1.87% Lanoteplase-treated patients (ns); haemorrhagic stroke rates were 0.64% alteplase and 1.12% Lanoteplase (P=0.004). The net clinical deficit of 30-day death or non-fatal disabling stroke was 7.0% and 7.2%, respectively. By 6 months, 8.8% of alteplase-treated patients and 8.7% of Lanoteplase-treated patients had died. Conclusion Single-bolus weight-adjusted Lanoteplase is an effective thrombolytic agent, equivalent to alteplase in terms of its impact on survival and with a comparable risk-benefit profile. The single-bolus regimen should shorten symptoms to treatment times and be especially convenient for emergency department or out-of-hospital administration. (C) 2000 The European Society of Cardiology.
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evaluation of a weight adjusted single bolus plasminogen activator in patients with myocardial infarction a double blind randomized angiographic trial of Lanoteplase versus alteplase
Circulation, 1998Co-Authors: Den P Heijer, Ettore Ambrosioni, F Vermeer, Z Sadowski, Jose Lopezsendon, R Von Essen, P Beaufils, Udho Thadani, Jennifer Adgey, Luc PierardAbstract:Background —Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. Methods and Results —InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted Lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of Lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P <0.001). Similar results were observed at 90 minutes (26.1% to 57.1%, P <0.001). At 90 minutes, coronary patency (TIMI 2 or 3) increased across the dose range up to 83% of subjects at 120 kU/kg Lanoteplase compared with 71.4% with alteplase. Thus, at this dose, Lanoteplase was superior to alteplase in restoring coronary patency (difference, 12%; 95% CI, 1% to 23%). The early safety experience in this study suggests that Lanoteplase was well tolerated at all doses with safety comparable to that of alteplase. Conclusions —Lanoteplase, a single-bolus, weight-adjusted agent, increased coronary patency at 60 and 90 minutes in a dose-dependent fashion. Coronary patency at 90 minutes was achieved more frequently with 120 kU/kg Lanoteplase than alteplase. In this study, safety with Lanoteplase and alteplase was comparable. InTIME-II, a worldwide mortality trial, will evaluate efficacy and safety with this promising new agent.
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Evaluation of a Weight-Adjusted Single-Bolus Plasminogen Activator in Patients With Myocardial Infarction A Double-Blind, Randomized Angiographic Trial of Lanoteplase Versus Alteplase
Circulation, 1998Co-Authors: P. Den Heijer, Ettore Ambrosioni, F Vermeer, Z Sadowski, R Von Essen, P Beaufils, Udho Thadani, Jennifer Adgey, Jl Lopez-sendon, Luc PierardAbstract:Background —Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. Methods and Results —InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted Lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of Lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P
Robert P. Giugliano - One of the best experts on this subject based on the ideXlab platform.
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Availability of on-site catheterization and clinical outcomes in patients receiving fibrinolysis for ST-elevation myocardial infarction
European heart journal, 2001Co-Authors: Joan Llevadot, Robert P. Giugliano, Elliott M. Antman, Robert G. Wilcox, Enrique P. Gurfinkel, Andrew Charlesworth, S.l Thompson, Timothy D. Henry, Carolyn H. Mccabe, Jose C. NicolauAbstract:Aims To compare management and clinical outcomes in hospitals stratified by the availability of on-site catheterization in InTIME-II, a multicentre trial comparing alteplase with Lanoteplase for acute myocardial infarction. Methods and Results We studied 15–078 patients enrolled in 35 countries and 855 hospitals. Thirty-one percent of hospitals had 24-h, 25% day-only, and 44% no on-site catheterization facilities. Rates of cardiac angiography (57%, 38%, 26%) and revascularization (37%, 21%, 17%) were higher in hospitals with increasing access to on-site facilities ) Conclusions There is a marked variation in procedure use by the availability of on-site catheterization with no major differences in patient outcomes. There is a need for additional randomized trials in the current era to address both the appropriate selection of patients and timing of invasive procedures in ST-elevation acute myocardial infarction.
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Geographic variation in patient and hospital characteristics, management, and clinical outcomes in ST-elevation myocardial infarction treated with fibrinolysis. Results from InTIME-II.
European heart journal, 2001Co-Authors: Robert P. Giugliano, Joan Llevadot, Robert G. Wilcox, Enrique P. Gurfinkel, Colm Mccabe, Andrew Charlesworth, S.l Thompson, Elliott M. AntmanAbstract:Aims We examined the geographic variations in InTIME-II, a randomized double-blind trial comparing alteplase with Lanoteplase for myocardial infarction. Methods and Results We compared baseline characteristics, management, and outcomes in four regions (Western Europe, Eastern Europe, North America, and Latin America) and in countries with historically different management approaches (Germany vs the U.K., the U.S. vs Canada). Thirty-day mortality in Western Europe, Eastern Europe, North America and Latin America was 6.7%, 7.3%, 5.7%, 10.1%, P
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Bolus fibrinolytic therapy in acute myocardial infarction.
JAMA, 2001Co-Authors: Joan Llevadot, Robert P. Giugliano, Elliott M. AntmanAbstract:ContextNew bolus fibrinolytics derived from the human tissue-type plasminogen activator (tPA) have emerged as a means of dissolution of occlusive thrombosis associated with acute myocardial infarction.ObjectiveTo review the new bolus fibrinolytic drugs derived from tPA: reteplase, Lanoteplase, and tenecteplase.Data SourcesThe MEDLINE, EMBASE, and Current Contents databases were searched for articles from 1983 to 2001, using the index terms pharmacokinetics, pharmacodynamics, plasminogen activator, reteplase, Lanoteplase, and tenecteplase. Additional data sources included bibliographies of articles identified on MEDLINE, EMBASE, and Current Content, inquiry of experts and pharmaceutical companies, and preliminary data presented at recent national and international cardiology conferences.Study SelectionWe selected for review studies that evaluated the pharmacokinetics and pharmacodynamics of reteplase, Lanoteplase, and tenecteplase, and assessed the effects of these bolus fibrinolytic drugs on the angiographic and immediate and long-term outcomes of patients. Of 138 articles identified, 38 were analyzed.Data ExtractionData quality was determined by publication in the peer-reviewed literature or presentation at an official cardiology society–sponsored meeting.Data SynthesisTenecteplase and reteplase are comparable with accelerated infusion recombinant tPA in terms of efficacy and safety but more convenient because they are administered by bolus injection. Lanoteplase and heparin bolus plus infusion is as effective as tPA with regard to mortality, but the rate of intracranial hemorrhage is significantly higher.ConclusionGiven the ease of administration and the similar outcomes compared with accelerated infusion recombinant tPA, it is likely that a key component of contemporary reperfusion will include a bolus fibrinolytic.
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Lower-dose heparin with fibrinolysis is associated with lower rates of intracranial hemorrhage
American heart journal, 2001Co-Authors: Robert P. Giugliano, Christopher P. Cannon, Elliott M. Antman, Robert G. Wilcox, Carolyn H. Mccabe, Frans Van De Werf, Eugene BraunwaldAbstract:Abstract Background The optimal heparin dose as an adjunct to fibrinolysis and its role in causing intracranial hemorrhage (ICH) is unclear. Methods We reviewed the heparin regimens and rates of ICH in 3 sets of recent fibrinolytic trials: (1) studies with accelerated recombinant tissue plasminogen activator (TPA, alteplase) plus intravenous heparin, in which the heparin regimen was changed during the course of the trial; (2) phase III trials with accelerated TPA plus intravenous heparin; and (3) trials of new single-bolus fibrinolytic agents. Results Lower rates of ICH were observed among studies of accelerated TPA that reduced the heparin dose mid-trial (TIMI 9A → 9B: 1.87% → 1.07%, GUSTO-IIa → IIb: 0.92% → 0.71%, TIMI 10B: 2.80% → 1.16%). Rates of ICH with accelerated TPA gradually increased from GUSTO-I (0.72%) in 1990 to 1993 to ASSENT-2 (0.94%) in 1997 to 1998. However, this trend was reversed in InTIME-II, which used the lowest heparin dose and most aggressive activated partial thromboplastin time monitoring and observed an ICH rate of 0.64% with accelerated TPA. Lower ICH rates were also observed when the heparin dose was reduced with single-bolus tenecteplase (TNK-TPA) and Lanoteplase. Conclusions Nonrandomized comparisons with accelerated TPA suggest that lower doses of intravenous heparin are associated with lower rates of ICH. This observation also appears to apply to single-bolus TNK-TPA and novel plasminogen activator. A lower-dose, weight–adjusted heparin regimen (60 U/kg bolus; maximum, 4000 U; 12 U/kg per hour infusion; maximum, 1000 U/h) with earlier monitoring of activated partial thromboplastin time is currently recommended in the revised American College of Cardiology/American Heart Association myocardial infarction guidelines and should be used in clinical practice. (Am Heart J 2001;141:742-50.)
