TY - JOUR
T1 - Evaluation of a weight-adjusted single-bolus plasminogen activator in patients with myocardial infarction
T2 - A double-blind, randomized angiographic trial of lanoteplase versus alteplase
AU - Den Heijer, Peter
AU - Vermeer, Frank
AU - Ambrosioni, Ettore
AU - Sadowski, Zygmunt
AU - López-Sendón, José L.
AU - Von Essen, Rainer
AU - Beaufils, Philippe
AU - Thadani, Udho
AU - Adgey, Jennifer
AU - Pierard, Luc
AU - Brinker, Jeffrey
AU - Davies, Richard F.
AU - Smalling, Richard W.
AU - Wallentin, Lars
AU - Caspi, Abraham
AU - Pangerl, Andreas
AU - Trickett, Linda
AU - Hauck, Cynthia
AU - Henry, David
AU - Chew, Paul
PY - 1998/11/17
Y1 - 1998/11/17
N2 - 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 - In TIME (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.
AB - 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 - In TIME (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.
KW - Myocardial infarction
KW - Plasminogen activators
KW - Reperfusion
KW - Thrombolysis
KW - Trials
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U2 - 10.1161/01.CIR.98.20.2117
DO - 10.1161/01.CIR.98.20.2117
M3 - Article
C2 - 9815865
AN - SCOPUS:0032542048
SN - 0009-7322
VL - 98
SP - 2117
EP - 2125
JO - Circulation
JF - Circulation
IS - 20
ER -