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(Circulation. 2000;102:1761.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Survival Outcomes 1 Year After Reperfusion Therapy With Either Alteplase or Reteplase for Acute Myocardial Infarction

Results From the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) III Trial

Eric J. Topol, MD; E. Magnus Ohman, MD; Paul W. Armstrong, MD; Robert Wilcox, MD; Alan M. Skene, PhD; Philip Aylward, MD; John Simes, MD; Anthony Dalby, MD; Amadeo Betriu, MD; Christoph Bode, MD; Harvey D. White, MD; Judith S. Hochman, MD; Hakan Emanuelson, MD; Alec Vahanian, MD; Shelly Sapp, MS; Amanda Stebbins, MS; David J. Moliterno, MD; Robert M. Califf, MD; on Behalf of the GUSTO-III Investigators¹

From The Cleveland Clinic Foundation, Cleveland, Ohio (E.J.T., D.J.M., S.S.); Duke University, Durham, NC (E.M.O., A.S., R.M.C.); University of Alberta, Edmonton, Canada (P.W.A.); Queen’s Medical Center University Hospital, Nottingham, UK (R.W.); Nottingham Clinical Trials Data Center, Nottingham, UK (A.M.S.); Flinders Medical Center, Bedford Park, Australia (P.A.); University of Sydney, New South Wales, Australia (J.S.); Milpark Hospital, Johannesburg, South Africa (A.D.); Hospital Clinic, University of Barcelona, Barcelona, Spain (A.B.); Medical Clinic of the University of Heidelberg, Heidelberg, Germany (C.B.); Green Lane Hospital, Auckland, New Zealand (H.D.W.); St Lukes-Roosevelt Hospital Center, New York, NY (J.S.H.); Astra Charnwood Clinical R & D, Loughborough, UK (H.E.); and Hospital Bichat, Paris, France (A.V.).

Correspondence to Eric J. Topol, MD, Department of Cardiology, Cleveland Clinic Foundation, Desk F25, 9500 Euclid Ave, Cleveland, OH 44195. E-mail topole{at}ccf.org

Background—New recombinant plasminogen activators have been developed to simulate the fibrinolytic action of the physiological serine protease tissue plasminogen activator (alteplase, t-PA), and have prolonged half-life features permitting bolus administration. One such activator, reteplase (r-PA), was compared with t-PA in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-III Trial.

Methods and Results—At 1-year follow-up, survival status was ascertained in 97.4% of the 15 059 patients enrolled in the GUSTO-III trial. At 1 year, the mortality rate for the t-PA–assigned group was 11.06%, and for r-PA it was 11.20% (P=0.77). The absolute mortality difference of 0.14% has 95% CIs of -1.21% to 0.93%. There were no significant differences in outcome by intention-to-treat for the 2 different plasminogen activators in the prespecified groups (age, infarct location, time-to-treatment). The absolute difference in mortality rates between t-PA and r-PA progressively narrowed over the predetermined observation times after random assignment; it was 0.31% at 24 hours, 0.26% at 7 days, 0.23% at 30 days, and 0.14% at 1 year. Of note, mortality rate in the trial between 30 days and 1 year in 13 883 patients was 4.02% and did not differ between the treatment groups. However, this mortality rate was substantially greater than in GUSTO-I, in which mortality rate for t-PA versus streptokinase between 30 days and 1-year was 2.97% (heart rate 1.36, 95% CI 1.23, 1.50, P<0.001).

Conclusions—The r-PA and t-PA strategies yielded similar survival outcomes after 30 days in this trial. The increase in mortality rate during extended follow-up compared with previous trials may reflect higher-risk patients and highlights the need for improved secondary prevention strategies.

Key Words: reperfusion • myocardial infarction • plasminogen activators

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