(Circulation. 1998;98:2117-2125.)
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports |
Evaluation of a Weight-Adjusted Single-Bolus Plasminogen Activator in Patients With Myocardial Infarction
A Double-Blind, Randomized Angiographic Trial of Lanoteplase Versus Alteplase
Presented in part at the Scientific Session of the American College of Cardiology, March 17, 1997.
From the University Hospital Groningen, Netherlands (P.d.H.); Academic Hospital Maastricht, Netherlands (F.V.); Universita degli Studi de Bologna, Italy (E.A.); Instytut Kardiologii, Warsaw, Poland (Z.S.); Hospital Gregorio Marañón, Madrid, Spain (J.L.L.-S.); Stiftsklinikum Augustinum, Munich, Germany (R.v.E.); Hôpital Lariboisière, Paris, France (P.B.); VA Medical Center, Oklahoma City, Okla (U.T.); Royal Victoria Hospital, Belfast, Ireland (J.A.); Centre Hospitalier Universitaire du Sart Tilman, Liège, Belgium (L.P.); Johns Hopkins Hospital, Baltimore, Md (J.B.); University of Ottawa Heart Institute, Ottawa, Ontario, Canada (R.F.D.); University of Texas Medical School, Houston (R.W.S.); Akademiska Sjukhuset, Uppsala, Sweden (L.W.); Heart Institute, Kaplan Hospital, Rehovot, Israel (A.C.); Bristol-Myers Squibb Co, Munich, Germany (A.P.); Bristol-Myers Squibb Co, Waterloo, Belgium (L.T.); and Bristol-Myers Squibb Co, Princeton, NJ (C.H., D.H., P.C.). Peter den Heijer is now at Ignatius Ziekenhuis, Breda, Netherlands.
Correspondence to Paul Chew, MD, Bristol-Myers Squibb, PO Box 4000, Princeton, NJ 08540.
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.
Key Words: plasminogen activators • thrombolysis • reperfusion • myocardial infarction • trials
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