Journal of the American College of Cardiology
16, 2014
2014 by the American College of Cardiology Foundation
Published by Elsevier Inc.
EDITORIAL COMMENT
As REGARDS
Treatment Goal
Attainment Compared
With COURAGE
The Perfect Should Not Be
the Enemy of the Good*
David J. Maron, MD,y William E. Boden, MDz
Stanford, California; and Albany, New York
The purpose of treating patients with stable ischemic heart
disease (SIHD) is to improve prognosis and quality of life.
Evidence-based management should include comprehensive
lifestyle change, control of risk factors, and pharmacological
therapy (1). Yet, many have questioned whether achieve-
ment of these worthy goals is attainable only in the context
of randomized clinical trials and whether such achieved
targets can be replicated in real-world clinical practice. A
corollary question is this: Is it realistic to expect perfection in
secondary prevention when applied broadly to multiple
treatment targets?
See page 1626
In this issue of the Journal, Brown et al. (2) report on the
proportion of patients with SIHD enrolled in the REGARDS
(REasons for Geographic and Racial Differences in Stroke)
prospective cohort study who achieved 7 treatment goals
specied in the COURAGE (Clinical Outcomes Utilizing
Revascularization and Aggressive Drug Evaluation) trial.
Among 3,167 adults with SIHD enrolled in the REGARDS
study between 2003 and 2007, attainment of 7 treatment goals
from the COURAGE trial was ascertained: aspirin use; blood
pressure <130/85 mm Hg (<80 mm Hg if diabetic); low-
density lipoprotein cholesterol (LDL-C) <85 mg/dl, high-
density lipoprotein cholesterol (HDL-C) 40 mg/dl, and
triglycerides (TG) <150 mg/dl; fasting glucose <126 mg/dl
(a surrogate for the COURAGE trial goal of glycosylated
*Editorials published in the Journal of the American College of Cardiology reect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From the yDepartment of Medicine, Stanford University School of Medicine,
Stanford, California; and the zDepartment of Medicine, Samuel S. Stratton VA
Medical Center, Albany Medical Center, and Albany Medical College, Albany, New
York. Both authors have reported that they have no relationships relevant to the
contents of this paper to disclose.
Vol. 63, No.
ISSN 0735-1097/$36.00
http://dx.doi.org/10.1016/j.jacc.2014.01.047
hemoglobin <7% in diabetics); nonsmoking status; body
mass index (BMI) <25 kg/m2 (the COURAGE trial goal
was 10% relative weight loss if the baseline BMI was
>27.5 kg/m2); and exercise 4 days per week (a surrogate for
the COURAGE trial goal of 30 to 45 min of moderate-
intensity physical activity 5 times per week). The median
number of goals achieved in the REGARDS study was 4,
whereas <25% met 5 goals, and only 0.5% met all 7 goals.
Without question, the bar set by the authors in their pri-
mary analysis was exceedingly high. First, the authors required
perfection in reaching all 7 goals (which, in reality, were 10,
with 2 components to the blood pressure target (systolic and
diastolic) and 3 components to the lipid target (LDL-C,
HDL-C, and TG). Understandably, this led to a very low
overall success rate. Second, by using COURAGE trial goals
rather than professional society secondary prevention goals
then in effect (3), the authors likely overestimated the com-
posite target failure rate because COURAGE trial goals were
somewhat more aggressive and because they interpreted
the goals more strictly than the COURAGE investigators.
Third, there was no hierarchical weighting of risk factors such
that achievement of glycemic, HDL-C, and TG goals were
accorded the same importance as blood pressure, LDL-C,
and smoking goals, despite robust evidence to the contrary.
For example, current secondary prevention guidelines (1,4)
have downgraded glycemic control to a class II recommen-
dation, although not even recognizing HDL-C and TG as
therapeutic goals due to lack of clinical trial evidence.
These results are neither unique nor unexpected. Other
observational studies have shown similar suboptimal adher-
ence to evidence-based secondary prevention therapies and
risk factor goal attainment (58), including worse outcomes
with low adherence (5,6). In a recent analysis of 3 federally
funded randomized trials of patients with diabetes, the rates of
simultaneously achieving guideline-based, protocol-driven
treatment targets for systolic blood pressure, LDL-C,
smoking cessation, and hemoglobin A1c at 1 year of follow-
up ranged from 8% to 23% (9). We decided to reanalyze
data from the COURAGE trial to see what proportion of
patients achieved all 7 treatment goals (actually 9 for non-
diabetics and 10 for diabetics). Among nondiabetic patients,
only 0.2% (n 5) were at target for all goals at baseline and
1.9% (n 39) achieved these at 1 year. Among diabetic pa-
tients, only 0.1% (n 1) was at target for all goals (including
glycosylated hemoglobin) at baseline, whereas 0.6% (n 4)
reached these at 1 year. Hence, even among presumably more
motivated patients participating in clinical research, for whom
free medications were provided, the rate of achieving multiple
risk factor goals was just as disappointing as unselected pa-
tients in real-world clinical practice. These sobering results
indicate that, despite decades of intensive research to identify
risk factors and prove the benets of controlling them, we
struggle mightily to translate evidence-based scientic
knowledge into routine clinical practice.
We can, however, view the current study results through
a more optimistic lens. The discouraging nding that <1%
JACC Vol. 63, No. 16, 2014
April 29, 2014:16345
of patients met all targeted risk factors devalues the success
observed in the REGARDS study. For example, a secondary
analysis that focused on attainment of 3 Class I recom-
mendations (aspirin use, systolic and diastolic blood pressure
control, and LDL-C control) revealed that 91% of partici-
pants met at least 1 of these 4 goals. The free-living
American adults with SIHD who were surveyed for the
REGARDS study were not dissimilar from the patients who
volunteered to participate in the COURAGE trial. In the
REGARDS study, 38% had an LDL-C <85 mg/dl at the
time of enrollment compared with 28% in the COURAGE
trial at the time of randomization, yet that proportion of
patients in the COURAGE trial increased to 70% after 5
years (10), indicating reason for optimism.
Although skepticism persists that the treatment targets
achieved in the COURAGE trial can be replicated in the
real world, we need to also recognize that it may be unre-
alistic to achieve each and every goal and that success in
secondary prevention need not be measured in binary terms
(all or nothing). As such, we should not fall prey to the
aphorism that the perfect is the enemy of the good. We
should recognize the value of achievement of individual
Class I recommendations for secondary prevention. The
more ambitious, broad-based success that we all seek can
only be achieved by designing and implementing better
strategies to improve guideline adherence at the patient,
provider, and system levels (11). New models of team-based
healthcare delivery are needed to achieve enhanced adher-
ence to multiple treatment goals, ultimately in the context of
a more enlightened healthcare system that rewards quality
and outcomes for both patients and physicians. Clearly, this
will require a multidisciplinary effort among multiple con-
stituents, including clinicians, healthcare researchers, poli-
cymakers, and population scientists, to bridge the remaining
gaps between evidence-based medicine and clinical practice.
With REGARDS to these noteworthy challenges, let us
not lose the COURAGE and conviction that we need to
identify new ways of doing better.
Reprint requests and correspondence: Dr. David J. Maron, Falk
Cardiovascular Research Center 289, 300 Pasteur Drive, Stanford,
California 94305. E-mail: david.maron@stanford.edu.
Maron and Boden 1635
Perfect Should Not Be the Enemy of Good
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Key Words: coronary artery disease - prevention - risk factors.