Evidence-Based Care for All Patients
Karen P. Alexander, MD, Eric D. Peterson, MD, MPH
Evidence-based medicine is the conscientious and judicious
use of current best evidence from clinical care research in the
management of individual patients.
Sackett et al. (1)
O
ver the past three decades, large randomized tri-
als have expanded our armamentarium of safe
and effective therapies for cardiovascular dis-
ease. These therapeutic advances have reduced mortality
from heart disease and stroke by more than half (2).
However, Rathore and colleagues in this issue of the Jour-
nal remind us that there is still considerable work to be
done before patients of all ages can expect to receive
proven cardiac therapies in routine practice (3).
Using the data from the Cooperative Cardiovascular
Project, Rathore et al. explore acute and discharge medi-
cine use in a large cohort of Medicare patients with acute
myocardial infarction. The study’s strengths include ac-
cess to a large, community-based patient population, de-
tailed clinical data, and state-of-the-art analytic methods.
The study, which focuses on the association between age
and the use of evidence-based medications, has several
notable observations.
First, patients with myocardial infarction enrolled in
randomized trials differ from those treated in community
practice. The elderly (age ⱖ75 years) have traditionally
been underrepresented in cardiovascular clinical trial
populations (4). Although there has been recent im-
provements in this area, 60% of trials of myocardial in-
farction in the last decade still failed to enroll any patient
over the age of 75 years (5). Even when the elderly are
included, their representation tends to be selective. For
example, in the Global Use of Strategies to Open Oc-
cluded Coronary Arteries (GUSTO-I) study, 40% of pa-
tients were aged ⱖ65 years and 12% were aged ⱖ75 years
(6). In comparison, 65% of patients with myocardial in-
farction in community practice are aged ⱖ65 years and
37% are aged ⱖ75 years (7). A comparison of patients
aged ⱖ65 years in the GUSTO study and those in the
current study further demonstrates trial selection biases.
For example, nearly 100% of the GUSTO sample pre-
sented within 6 hours from symptom onset (a criterion
for enrollment) compared with 50% of patients from the
Cooperative Cardiovascular Project. Patients in the Co-
operative Cardiovascular Project were also more likely to
Am J Med. 2003;114:333–335.
From the Duke Clinical Research Institute, Durham, North Carolina.
Requests for reprints should be addressed to Eric D. Peterson, MD,
MPH, Duke Clinical Research Institute, Box 17969, Durham, North
Carolina 27715, or peter016@mc.duke.edu.
Manuscript submitted October 26, 2002.
©2003 by Excerpta Medica Inc.
All rights reserved.
have diabetes mellitus (31% vs. 15%) and hypertension
(62% vs. 45%) and be in Killip class ⬎II (37% vs. 5%)
than were those in the GUSTO-I study (8). Additionally,
6% of patients in the Cooperative Cardiovascular Project
had dementia and 20% needed assistance with mobility,
which is unusual for subjects enrolled in clinical trials. In
general, this limited and selective representation of the
elderly in trials contributes to concerns about the gener-
alizability of trial findings to real-world practice.
Second, there is underutilization of evidence-based
care in patients of all ages. Using strict criteria, Rathore et
al. defined “ideal” candidates for treatment as those with-
out any potential contraindication. These conservative
definitions removed many patients from the perfor-
mance assessment, excluding nearly 90% from assess-
ments of thrombolytic therapy and 67% from assess-
ments of use of beta-blockers at hospital discharge. Even
among these “ideal” patient subsets, only half received
potentially life-saving interventions, such as thrombo-
lytic therapy or beta-blockers. Similarly, 25% to 40% of
“ideal” subjects failed to receive secondary prevention
medications, including aspirin, beta-blockers, or angio-
tensin-converting enzyme (ACE) inhibitors at discharge.
Finally, the study reflects care patterns from the mid-
1990s, and guideline adherence rates may have improved.
Regardless, the degree of undertreatment observed by
Rathore et al. is still alarming as each therapy was well
established as beneficial before the study period.
Third, inequalities in evidence-based care for myocar-
dial infarction increase with age. Rathore et al. demon-
strated that the very elderly are particularly vulnerable to
undertreatment. Even among “ideal” candidates, there
was a consistent decrease in the use of evidenced-based
treatments as age increased from 65 to ⬎85 years. These
age-related treatment gaps ranged from 15% for dis-
charge aspirin to as much as 40% for thrombolytic ther-
apy. This decrease in treatment with age may be explained
by several factors: very elderly patients with myocardial
infarction present later, are more ill, and have more co-
morbid conditions—which may reduce candidacy for
treatment. After adjustment for patient clinical factors,
the age-associated treatment differences diminished for
certain therapies (aspirin and ACE inhibitors), but per-
sisted for others (beta-blockers and thrombolytics). Ad-
ditionally, very elderly patients are less likely to be treated
at hospitals with catheterization laboratories or cardiolo-
gists, which are known to affect care patterns and out-
comes (9,10). Yet the age-related differences remained
after the authors adjusted further for physician and treat-
ing hospital.
Age itself is an independent determinant of cardiovas-
0002-9343/03/$–see front matter 333
doi:10.1016/S0002-9343(03)00069-X
 Evidence-Based Care for All Patients/Alexander and Peterson
cular care. Owing to limitations inherent in retrospective
chart review studies, the current analysis cannot fully ex-
clude other factors (such as patient preferences and
health care resources) that may confound analyses. The
data seem to identify an age-related treatment threshold
of about 75 years, beyond which care patterns are affected
by age rather than by their clinical condition. This was
evident for high-risk therapies, such as thrombolytic
therapy, cardiac catheterization, or revascularization
procedures (11). When treating the very elderly, clini-
cians more often recall the rare but serious complications
of intervention than the many (unseen) deaths that could
be avoided. In following the Hippocratic doctrine of “do
no harm,” physicians may unintentionally cause greater
harm by withholding beneficial therapies. Recent studies
have confirmed that the benefits of many medications
(aspirin, lipid-lowering beta-blockers, and ACE inhibi-
tors) outweigh their risks even among very elderly pa-
tients (12–16). Even invasive diagnostic and revascular-
ization strategies have been shown to provide similar
benefits in elderly patients as in younger patients (17–19).
It is hoped that these recent analyses will help to dispel the
notion that these therapies are only effective in the young.
This study should provide a motivating force to im-
prove the delivery of evidence-based care for all patients
with myocardial infarction in the United States. Future
clinical trials should be designed to be representative of
the patients treated in the community. Recently com-
pleted trials have shown the feasibility of including a large
proportion of very elderly patients in the study sample, as
well as of conducting trials exclusively in the elderly
(13,20,21). Future research should focus on defining the
causes for these age-related differences in care, as well as
on how to overcome these disparities. In such research,
physicians would need to document more clearly which
therapies were considered and why care may have devi-
ated from the standard. The development of clinical de-
cision aids may also help clinicians to determine the risks
and benefits of treatment in elderly patients, thus sup-
porting more empirical and rational care decisions. The
Thrombolytic Predictive Instrument, which provides
bedside feedback on the risks and benefits of thrombolyt-
ics in myocardial infarction, is an example of such a tool
and has had a positive effect on the use of thrombolytics
(22).
In conclusion, continuing national registries such as
the Cooperative Cardiovascular Project will enable us to
monitor cardiovascular trends and identify disparities in
care as well as areas for quality improvement. As exem-
plified by the current study, quality measurement needs
to focus on care patterns in the general population and in
understudied populations (e.g., women, racial or ethnic
minorities, and the elderly) (23). Caregivers will need to
act on the data, implementing continuous quality im-
provement efforts within their hospital and office envi-
334 March 2003 THE AMERICAN JOURNAL OF MEDICINE威 Volume 114
ronments. This way we can ensure that patients of all ages
routinely receive the very best evidence-based care.
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