Variations in patient management and outcomes for acute myocardial infarction in the United States and other countries. Results from the GUSTO trial. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries

JAMA. 1995 May;273(20):1586-91. doi: 10.1001/jama.273.20.1586.


Objective: To examine differences in outcomes and patient management between patients in the United States and outside the United States undergoing thrombolysis for acute myocardial infarction.

Design, setting, and patients: Patients in the United States (n = 23,105) and 14 other countries (n = 17,916) were randomized to receive streptokinase plus either subcutaneous or intravenous (IV) heparin, accelerated recombinant tissue-type plasminogen activator (rt-PA) plus IV heparin, or combined streptokinase and rt-PA plus IV heparin.

Outcome measures: Differences in 30-day mortality and patient management were compared among treatments and between US and non-US patients. Treatment-by-country interactions were assessed by logistic regression analyses. Expected mortality of US and non-US patients was estimated using a predictive model and was compared with observed mortality.

Results: Mortality reduction with accelerated rt-PA vs streptokinase was greater in the United States (1.2% absolute decrease vs 0.7% elsewhere), but the test for treatment-by-country interaction against streptokinase was not significant (P = .30). Benefits of accelerated rt-PA over combination therapy were observed in the United States, but not in other countries (P = .02). Despite differences in base-line characteristics and patient management, 30-day mortality was not significantly different: 6.8% in the United States vs 7.2% elsewhere (P = .09). After adjustment for baseline differences, observed vs predicted outcomes were slightly better in the United States (6.8% vs 7.0%) than elsewhere (7.2% vs 7.0%), indicating that enrollment in the United States was a marginally significant predictor of better survival (P = .047).

Conclusions: No significant evidence for a differentially greater benefit of accelerated rt-PA over streptokinase was found in US vs non-US patients. However, increased procedure and treatment use in the United States was associated with only a small decrease in short-term mortality. Long-term follow-up is required to clarify the relationship between survival and the more intensive US management approach.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Australia
  • Belgium
  • Canada
  • Drug Therapy, Combination
  • Female
  • France
  • Germany
  • Heparin / administration & dosage
  • Heparin / therapeutic use*
  • Humans
  • Ireland
  • Israel
  • Logistic Models
  • Luxembourg
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / mortality*
  • Myocardial Infarction / therapy
  • Netherlands
  • New Zealand
  • Poland
  • Recombinant Proteins / therapeutic use
  • Spain
  • Streptokinase / administration & dosage
  • Streptokinase / therapeutic use*
  • Survival Analysis
  • Switzerland
  • Thrombolytic Therapy*
  • Tissue Plasminogen Activator / administration & dosage
  • Tissue Plasminogen Activator / therapeutic use*
  • Treatment Outcome
  • United Kingdom
  • United States


  • Recombinant Proteins
  • Heparin
  • Streptokinase
  • Tissue Plasminogen Activator