Is there evidence of implicit exclusion criteria for elderly subjects in randomized trials? Evidence from the GUSTO-1 study

Harlan M. Krumholz, Cary P. Gross, Eric D. Peterson, Hal V. Barron, Martha J. Radford, Lori S. Parsons, Nathan R. Every

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Background: Some experts have raised concerns about the ability to generalize randomized trials, emphasizing that patients who participate in these studies are often not representative of those seen in clinical practice, particularly in the case of elderly patients. To determine the effect of implicit exclusion criteria on a trial study sample, we compared data from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial with data from a retrospective registry from selected hospitals, the National Registry of Myocardial Infarction (NRMI), and a nationally representative study of myocardial infarction care, the Cooperative Cardiovascular Project (CCP). Methods: We compared GUSTO subjects aged 65 years and older who were enrolled in the United States with similarily aged patients in the 2 observational studies who met the trial's eligibility criteria. We examined baseline characteristics, clinical presentation, treatments, procedures, clinical events, and in-hospital mortality rates. Results: We found modest, although significant, differences between patients in NRMI, CCP, and GUSTO in demographic and clinical characteristics, treatment, and outcome. For example, GUSTO patients were significantly younger (73.1 ± 5.7 vs 74.7 ± 6.8 for NRMI and 75.8 ± 7.2 for CCP), less likely to have Killip class III/IV at presentation (3.1% vs 6.2% for NRMI and 32.7% for CCP), and more likely to receive aspirin (95.5% vs 86.3% for NRMI and 86.5% for CCP) and β-blockers (71.9% vs 43.5% for NRMI and 52.7% for CCP). Overall, NRMI and CCP patients had a lower risk of 30-day mortality after adjustment for demographic, clinical, and hospital characteristics than patients in GUSTO (odds ratio, 0.79; 95% CI, 0.73-0.86 for NRMI; odds ratio, 0.65; 95% CI, 0.59-0.71 for CCP). Conclusions: Older patients enrolled in a randomized trial without an age restriction had many similarities compared with patients seen in clinical practice. The higher mortality rate of the GUSTO patients does not support the hypothesis that the trial enrolled a healthier cohort than is seen in practice.

Original languageEnglish (US)
Pages (from-to)839-847
Number of pages9
JournalAmerican heart journal
Issue number5
StatePublished - Nov 2003
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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