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Are international differences in the outcomes of acute coronary syndromes apparent or real? A multilevel analysis
  1. Wei-Ching Chang1,
  2. William K Midodzi1,
  3. Cynthia M Westerhout1,
  4. Eric Boersma2,
  5. Judith Cooper3,
  6. Elliot S Barnathan3,
  7. Maarten L Simoons2,
  8. Lars Wallentin4,
  9. E Magnus Ohman5,
  10. Paul W Armstrong1,
  11. for the GUSTO-IV ACS Investigators
  1. 1University of Alberta, Edmonton, Alberta, Canada
  2. 2Erasmus Medical Centre, Rotterdam, Netherlands
  3. 3Centocor, Malvern, Pennsylvania, USA
  4. 4Uppsala Clinical Research Centre, Uppsala, Sweden
  5. 5University of North Carolina, Chapel Hill, North Carolina, USA
  1. Correspondence to:
 Dr P W Armstrong
 2-51 Medical Sciences Building, University of Alberta, Edmonton, Alberta T6G 2H7, Canada;


Study objective: International variation in the outcomes of patients with acute coronary syndromes (ACS) has been well reported. The relative contributions of patient, hospital, and country level factors on clinical outcomes, however, remain unclear, and thus, was the objective of this study.

Design: Multilevel logistic regression models were developed for death/(re)infarction (MI) at 30 days and death in one year, with patients (1st level) nested in hospitals (2nd level) and hospitals in countries (3rd level).

Settings: The GUSTO IV ACS clinical trial was carried out at 458 hospital sites in 24 countries.

Patients: 7800 non-ST segment elevation (NSTE) ACS patients.

Main results: There were substantial variations among countries in the processes and outcomes of care at 30 days, ranging from 5.4% to 50.0% for percutaneous coronary intervention, 4.3% to 21.2% for coronary artery bypass graft surgery, 5.0% to 13.9% for 30 day death/(re)MI, and 4.9% to 14.8% for one year mortality. However, the residual inter-country variations in 30 day death/(re)MI and one year mortality became non-significant and nearly disappeared (p>0.500 for both) after adjusting for key baseline patient characteristics and hospital factors, which became significant (p<0.01 for both). Patient level factors accounted for 96%–99% of total variation in these end points, leaving the remaining 1% and 4% of variance attributable to hospital level factors.

Conclusion: The international differences in clinical outcomes in this study of NSTE ACS are primarily accounted for by the patient level factors, with hospital level factors playing a minor part, and the country level factors a negligible one. These findings have significant policy and research implications involving international collaboration and comparisons.

  • NSTE, non-ST segment elevation
  • ACS, acute coronary syndrome
  • GUSTO IV ACS, global utilisation of strategies to open occluded coronary arteries IV acute coronary syndromes trial
  • PCI, percutaneous coronary intervention
  • CABG, coronary artery bypass graft
  • PCV, proportional change in variance
  • ICC, intraclass correlation coefficient
  • MI, myocardial infaction
  • STEMI, ST segment elevation myocardial infarction
  • international differences
  • acute coronary syndromes
  • multilevel modelling

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  • Funding: Eli Lilly/Canada. Research grants were received from Centocor, Malvern, PA.

  • Conflicts of interest: none declared.

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