(Circulation. 1996;94:891-898.)
© 1996 American Heart Association, Inc.
Articles |
Randomized Comparison of Coronary Thrombolysis Achieved With Double-Bolus Reteplase (Recombinant Plasminogen Activator) and Front-Loaded, Accelerated Alteplase (Recombinant Tissue Plasminogen Activator) in Patients With Acute Myocardial Infarction
the Medizinische Klinik III (Kardiologie) (C. Bode), Universitat Heidelberg (Germany); University of Texas Medical School (Houston) (R.W.S.); Klinikum der Universitat Homburg (Germany) (G.B.); Highline Community Hospital (C. Burnett), Seattle, Wash; Valley Medical Center (G.L.), Renton, Wash; St Francis Hospital (J.M.K.), Tulsa, Okla; Taylor Hospital (R.C.), Ridley Park, Pa; Sacred Heart General Hospital (L.G.C.), Eugene, Ore; Munroe Regional Medical Center (R.L.F.), Ocala, Fla; Memorial Medical Center (A.A.S.), Jacksonville, Fla; and University of Washington Medical Center (W.D.W.) (Seattle).
Correspondence to Christoph Bode, MD, Medizinische Klinik III (Kardiologie), Universitat Heidelberg, Bergheimerstrasse 58, 69115 Heidelberg, Germany.
Background The therapeutic benefit of thrombolytic therapy has been shown to correlate directly with completeness (TIMI grade 3 flow) and speed of reperfusion of the infarct-related coronary artery. The purpose of the RAPID II study was to determine whether a double-bolus regimen of reteplase, a recently developed deletion mutant of wild-type tissue plasminogen activator, could improve 90-minute coronary artery patency rates achieved with the most successful standard regimen, an "accelerated" front-loaded infusion of alteplase.
Methods and Results Three hundred twenty-four patients with acute myocardial infarction were randomized to receive (along with intravenous heparin and aspirin) either a 10 plus 10 megaunits double bolus of reteplase or front-loaded alteplase. The primary end point of "patency at 90 minutes, graded according to the TIMI classification" was centrally assessed in a blinded fashion. Infarct-related coronary artery patency (TIMI grade 2 or 3) and complete patency (TIMI grade 3) at 90 minutes after the start of thrombolytic therapy were significantly higher in the reteplase-treated patients (TIMI grade 2 or 3: 83.4% versus 73.3% for front-loaded alteplase-treated patients, P=.03; TIMI grade 3: 59.9% versus 45.2%, P=.01). At 60 minutes, the incidence of both, patency and complete patency, was also significantly higher in reteplase-treated patients (reteplase versus alteplase, TIMI grade 2 or 3: 81.8% versus 66.1%, P=.01; TIMI grade 3: 51.2% versus 37.4%, P<.03). Reteplase-treated patients required fewer acute additional coronary interventions (13.6% versus 26.5%, P<.01), and 35-day mortality was 4.1% for reteplase and 8.4% for alteplase (P=NS). There were no significant differences between reteplase and alteplase in bleedings requiring a transfusion (12.4% versus 9.7%) or hemorrhagic stroke (1.2% versus 1.9%).
Conclusions Reteplase, when given as a double bolus of 10 plus 10 megaunits to patients with acute myocardial infarction, achieves significantly higher rates of early reperfusion of the infarct-related coronary artery and requires significantly fewer acute coronary interventions than front-loaded alteplase without an apparent increased risk of complications.
Key Words: thrombolysis • myocardial infarction • plasminogen activators
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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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|
|
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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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|
|
|
|
|
|
C. P. Cannon Overcoming thrombolytic resistance: Rationale and initial clinical experience combining thrombolytic therapy and glycoprotein IIb/IIIa receptor inhibition for acute myocardial infarction J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1395 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.J. Van de Werf The ideal fibrinolytic: can drug design improve clinical results? Eur. Heart J., October 2, 1999; 20(20): 1452 - 1458. [PDF]
|
|
|
|
|
|
E Straumann, S Yoon, B Naegeli, J Frielingsdorf, A Gerber, E Schuiki, and O Bertel Hospital transfer for primary coronary angioplasty in high risk patients with acute myocardial infarction Heart, October 1, 1999; 82(4): 415 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
J. K. French, T. A. Hyde, H. Patel, D. J. Amos, S. C. McLaughlin, B. J. Webber, and H. D. White Survival 12 years after randomization to streptokinase: the influence of thrombolysis in myocardial infarction flow at three to four weeks J. Am. Coll. Cardiol., July 1, 1999; 34(1): 62 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Gibson Primary Angioplasty Compared with Thrombolysis: New Issues in the Era of Glycoprotein IIb/IIIa Inhibition and Intracoronary Stenting Ann Intern Med, May 18, 1999; 130(10): 841 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Breuer, A. Schutz, B. Gansera, W. Eichinger, J. Weingartner, and B. Kemkes Intraoperative local fibrinolysis as emergency therapy after early coronary artery bypass thrombosis Eur. J. Cardiothorac. Surg., March 1, 1999; 15(3): 266 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Cannon, C. M. Gibson, C. H. McCabe, A. A. J. Adgey, M. J. Schweiger, R. F. Sequeira, G. Grollier, R. P. Giugliano, M. Frey, H. S. Mueller, et al. TNK–Tissue Plasminogen Activator Compared With Front-Loaded Alteplase in Acute Myocardial Infarction : Results of the TIMI 10B Trial Circulation, December 22, 1998; 98(25): 2805 - 2814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. den Heijer, F. Vermeer, E. Ambrosioni, Z. Sadowski, J. L. Lopez-Sendon, R. von Essen, P. Beaufils, U. Thadani, J. Adgey, L. Pierard, et al. 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, November 17, 1998; 98(20): 2117 - 2125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Brodie, T. D. Stuckey, T. C. Wall, G. Kissling, C. J. Hansen, D. B. Muncy, R. A. Weintraub, and T. A. Kelly Importance of time to reperfusion for 30-day and late survival and recovery of left ventricular function after primary angioplasty for acute myocardial infarction J. Am. Coll. Cardiol., November 1, 1998; 32(5): 1312 - 1319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. F. Lundergan, J. S. Reiner, W. F. McCarthy, K. S. Coyne, R. M. Califf, A. M. Ross, and for the GUSTO-I Angiographic Investigators Clinical predictors of early infarct-related artery patency following thrombolytic therapy: importance of body weight, smoking history, infarct-related artery and choice of thrombolytic regimen: the GUSTO-I experience J. Am. Coll. Cardiol., September 1, 1998; 32(3): 641 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. D. White and F. J. J. Van de Werf Thrombolysis for Acute Myocardial Infarction Circulation, April 28, 1998; 97(16): 1632 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. F. Gensini, M. Comeglio, and A. Colella Coronary and Peripheral Thrombolysis: Current Status and Recommendations Clinical and Applied Thrombosis/Hemostasis, April 1, 1998; 4(2): 82 - 86. [Abstract] [PDF]
|
|
|
|
 |
|
 R. L White Thrombolytic Therapy in Acute Myocardial Infarction Part II: 1997 Update Asian Cardiovasc Thorac Ann, March 1, 1998; 6(1): 03 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A H Gershlick and R S More Recent advances: Treatment of myocardial infarction BMJ, January 24, 1998; 316(7127): 280 - 284. [Full Text]
|
|
|
|
|
|
R. W. Smalling and H. V. Anderson Pathophysiological Insight Into the Possible Optimal Therapies for Acute Myocardial Infarction and Unstable Angina Circulation, January 13, 1998; 97(1): 10 - 11. [Full Text] [PDF]
|
|
|
|
|
|
The Global Use of Strategies to Open Occluded Coro A Comparison of Reteplase with Alteplase for Acute Myocardial Infarction N. Engl. J. Med., October 16, 1997; 337(16): 1118 - 1123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|