Mortality at 1 Year With Combination Platelet Glycoprotein IIb/IIIa Inhibition and Reduced-Dose Fibrinolytic Therapy vs Conventional Fibrinolytic Therapy for Acute Myocardial Infarction
GUSTO V Randomized Trial
- A. Michael Lincoff, MD;
- Robert M. Califf, MD;
- Frans Van de Werf, MD;
- James T. Willerson, MD;
- Harvey D. White, MD;
- Paul W. Armstrong, MD;
- Victor Guetta, MD;
- W. Brian Gibler, MD;
- Judith S. Hochman, MD;
- Christoph Bode, MD;
- Alec Vahanian, MD;
- P. Gabriel Steg, MD;
- Diego Ardissino, MD;
- Stefano Savonitto, MD;
- Frits Bar, MD;
- Zygmunt Sadowski, MD;
- Amadeo Betriu, MD;
- Joan E. Booth, RN;
- Kathy Wolski, MS;
- Michael Waller, MD;
- Eric J. Topol, MD;
- for the GUSTO V Investigators
- Author Affiliations: Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio (Drs Lincoff and Topol and Mss Booth and Wolski); Duke Clinical Research Institute, Durham, NC (Dr Califf); University Hospital Gasthuisberg, Leuven, Belgium (Dr Van de Werf); Houston Medical Center, Houston, Tex (Dr Willerson); Green Lane Hospital, Auckland, New Zealand (Dr White); University of Alberta Hospital, Edmonton (Dr Armstrong); Chaim Sheba Medical Center, Ramat Gan, Israel (Dr Guetta); University of Cincinnati Medical Center, Cincinnati, Ohio (Dr Gibler); St Luke's Hospital, New York, NY (Dr Hochman); Medizinische Universitatsklinik, Freiburg, Germany (Dr Bode); Hopital Tenon, Paris, France (Dr Vahanian); Hopital Bichat, Paris, France (Dr Steg); Azienda Ospedaliera Di Parma, Parma, Italy (Dr Ardissino); Ospedale Niguarda Ca' Granda, Milan, Italy (Dr Savonitto); Academisch Ziekenhuis Maastricht, Maastricht, Netherlands (Dr Bar); National Institute of Cardiology, Warsaw, Poland (Dr Sadowski); University of Barcelona Hospital Clinic, Barcelona, Spain (Dr Betriu); and Centocor Inc, Malvern, Pa (Dr Waller). A complete list of the investigators and participating centers was published previously (Lancet. 2001;357:1905-1914).
Abstract
Context Among patients with acute myocardial infarction, combination reperfusion therapy with a platelet glycoprotein IIb/IIIa receptor inhibitor (abciximab) and a half dose of a plasminogen activator (reteplase) did not significantly reduce mortality at 30 days compared with a full dose of reteplase. Rates of nonfatal ischemic complications were significantly diminished.
Objective To determine if the beneficial effects of abciximab and reteplase (combination therapy) on early nonfatal complications would translate into a reduction in the risk of death by 1 year.
Design, Setting, and Patients One-year follow-up of a randomized controlled trial (Global Use of Strategies To Open Coronary Arteries [GUSTO] V). Of 16 588 patients who had been treated in 820 community and referral hospitals in 20 countries between July 1999 and February 2001, mortality data were available for 16 453 (99.2%).
Intervention Patients were randomly assigned to receive (intravenously) a standard dose of reteplase (two 10-U boluses, 30 minutes apart) or the combination of a standard dose of abciximab (0.25 mg/kg bolus, 0.125 µg/kg per minute infusion [maximum 10 µg/min for 12 hours]) and a half dose of reteplase (two 5-U boluses, 30 minutes apart).
Main Outcome Measure One-year all-cause mortality rates.
Results All-cause mortality at 1 year occurred in 692 (8.38%) of 8260 patients in the reteplase group and 698 (8.38%) of the 8328 patients in the combination therapy group (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.90-1.11; P>.99). Reinfarction within the first 7 days occurred in 3.5% of patients in the reteplase group and 2.3% of patients in the combination therapy group, and was significantly associated with 1-year mortality (22.6% in patients with reinfarction vs 8.0% in patients without reinfarction; HR, 3.08; 95% CI, 2.53-3.75; P<.001). However, treatment assignment did not significantly influence time of mortality regardless of reinfarction status.
Conclusion Combination therapy (abciximab and reteplase) did not reduce mortality over 1 year compared with fibrinolytic therapy with reteplase alone.
