Context Elderly persons and women were underrepresented in randomized controlled
trials (RCTs) prior to 1990. Since then, efforts have been made to correct
these biases, but their effect is unclear.
Objective To determine whether the percentage of elderly persons and women in
published clinical trials of acute coronary syndromes has increased and how
this enrollment compared with disease prevalence.
Data Sources The MEDLINE and Cochrane databases were searched for English-language
articles from January 1966 to March 2000 regarding myocardial infarction,
unstable angina, or acute coronary syndromes. Additional data sources included
meta-analyses, review articles, and cardiology textbooks. Estimates of community-based
myocardial infarction rates came from the National Registry of Myocardial
Infarction and the Worcester Heart Study.
Study Selection Published RCTs of acute coronary syndrome patients were included and
trials enrolling 50 patients or fewer, those without clinical end points,
papers published in a language other than English, and unpublished manuscripts
were excluded. Of 7645 studies identified, 593 RCTs were selected for review.
Data Extraction The RCTs were abstracted by 2 of the authors for year of publication,
source of support (ie, funding), pharmacotherapy, study phase, number of study
sites, trial location, number of patients, mean age of the study population,
and any age exclusion criteria for enrollment.
Data Synthesis The number of published RCTs with explicit age exclusions has declined
from 58% during 1966-1990 to 40% during 1991-2000. Trial enrollment of patients
aged 75 years or older increased from 2% for studies published during 1966-1990
to 9% during 1991-2000, but remains well below their representation among
all patients with myocardial infarction (37%) in the United States. Enrollment
of women has risen from 20% for studies published between 1966-1990 to 25%
during 1991-2000, but remains well below their proportion of all patients
with myocardial infarction (43%) in the United States.
Conclusions Attempts at making cardiovascular RCTs more inclusive appear to have
had limited success; thus, women and elderly persons remain underrepresented
in published trial literature relative to their disease prevalence. Because
safety and efficacy can vary as a function of sex and age, these enrollment
biases undermine efforts to provide evidence-based care to all cardiac patients.