Copyright © 2000 by the European Society of Cardiology.
Intravenous NPA for the treatment of infarcting myocardium early. InTIME-II, a double-blind comparison of single-bolus lanoteplase vs accelerated alteplase for the treatment of patients with acute myocardial infarction
Received October 10, 2000; accepted October 16, 2000Abstract
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 6h of onset of ST elevation acute myocardial infarction.
Methods and Results 15078 patients were recruited from 855 hospitals worldwide and randomized in a 2:1 ratio to receive either lanoteplase 120KU.kg–1as a single intravenous bolus, or up to 100mg accelerated alteplase given over 90min. 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.
Key Words: Acute myocardial infarction, bolus lytic therapy, lanoteplase
References
- N Engl J Med. 1993;329:673–682
[Abstract/Free Full Text] - Califf RM, White HD, Van de Werf F. One-year results from the global utilisation of streptokinase and t-PA for occluded coronary arteries (GUSTO-I) Trial. Circulation. 1996;94:1233–1238
[Abstract/Free Full Text] - N Engl J Med. 1993;329:1615–1622
[Abstract/Free Full Text] - Hansen L, Blue Y, Barone K, Collen D, Larsen GR. Functional effects of asparagine-linked oligosaccharide on natural and variant human tissue-type plasminogen activator. J Biol Chem. 1988;263:15713–15719
[Abstract/Free Full Text] - Den Heijer P, Vermeer F, Ambrosioni E. 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. 1998;98:2117–2125
[Abstract/Free Full Text] - Lancet. 1995;346:329–336[CrossRef][ISI][Medline]
- N Engl J Med. 1997;337:1124–1130
[Abstract/Free Full Text] - Lancet. 1999;354:716–722[CrossRef][ISI][Medline]
- Cleveland WS, Devlin SJ. Locally weighted regression. An approach to regression analysis by local fitting. J Am Statist Assoc. 1988;83:596–610[CrossRef][ISI]
- Gurwitz JH, Gore JM, Goldberg RJ. Risk for intracranial hemorrhage after tissue plasminogen activator treatment for acute myocardial infarction. Participants in the National Registry of Myocardial Infarction 2. Ann Intern Med. 1998;129:597–604
[Abstract/Free Full Text] - Lancet. 1994;343:311–322[CrossRef][ISI][Medline]
- N Engl J Med. 1997;337:1118–1123
[Abstract/Free Full Text] - Lancet. 1988;2:349–360[Medline]
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|
|
|
|
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|
|
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|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
P. W. Armstrong and D. Collen Fibrinolysis for Acute Myocardial Infarction : Current Status and New Horizons for Pharmacological Reperfusion, Part 2 Circulation, June 19, 2001; 103(24): 2987 - 2992. [Full Text] [PDF]
|
|
|
|
|
|
P. W. Armstrong and D. Collen Fibrinolysis for Acute Myocardial Infarction : Current Status and New Horizons for Pharmacological Reperfusion, Part 1 Circulation, June 12, 2001; 103(23): 2862 - 2866. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Widimsky Pharmacological versus catheter-based reperfusion: What is present state of the art? Eur. Heart J. Suppl., June 1, 2001; 3(suppl_C): C47 - C54. [Abstract] [PDF]
|
|
|
|
|
|
P. W. Armstrong, C. Granger, and F. Van de Werf Bolus Fibrinolysis : Risk, Benefit, and Opportunities Circulation, February 27, 2001; 103(8): 1171 - 1173. [Full Text] [PDF]
|
|
|
|
|
|
F. Van de Werf In TIME-II: more than a study on lanoteplase Eur. Heart J., December 2, 2000; 21(24): 1996 - 1997. [PDF]
|
|
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