The End of the RiskTreatment Paradox?: A Rising Tide Lifts All Boats
Finlay A. McAlister
J. Am. Coll. Cardiol. 2011;58;1766-1767
doi:10.1016/j.jacc.2011.07.028
This information is current as of October 10, 2011
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Journal of the American College of Cardiology
© 2011 by the American College of Cardiology Foundation
Published by Elsevier Inc.
EDITORIAL COMMENT
The End of the
Risk–Treatment Paradox?
A Rising Tide Lifts All Boats*
Finlay A. McAlister, MD, MSC
Edmonton, Alberta, Canada
The risk–treatment paradox describes a treatment selection
bias in which low-risk individuals are more likely to receive
therapy than those patients at higher risk for poor outcomes
from the underlying condition. The implications of the
risk–treatment paradox are 2-fold. For clinicians, it is
important to consciously work to avoid the paradox because
the relative benefits of most therapies are similar across
patient subgroups defined by baseline risk, and thus the
absolute benefits of therapy are greatest in those patients at
highest baseline risk. For individuals conducting (or reading) comparative effectiveness research, the risk–treatment
paradox is an important source of confounding to be
cognizant of when drawing conclusions about treatment
effects on the basis of associations between treatment
See page 1760
exposure and outcomes. Observational studies can provide
spuriously high estimates of treatment benefit if the risk–
treatment paradox is manifest because low-risk patients are
both more likely to be exposed to the therapy of interest and
also less likely to experience the outcome regardless of therapy.
In this issue of the Journal, Motivala et al. (1) report data
from the Get With The Guidelines–Coronary Artery Disease (GWTG-CAD) program demonstrating that although
adherence with guideline-recommended care in U.S. patients with myocardial infarction has improved over the past
decade, a risk–treatment paradox remains in that those
patients with the poorest prognosis are also those least likely
to receive guideline-recommended care. However, the magnitude of the risk–treatment paradox declined over the years
studied, and it is worth noting that patients in the high-risk
tertile in 2008, who received the “poorest” quality of care in
*Editorials published in the Journal of the American College of Cardiology reflect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From the Division of General Internal Medicine and the Patient Health Outcomes
Research Institute, University of Alberta, Edmonton, Alberta, Canada. Dr. McAlister
is supported by a career salary award from the Alberta Heritage Foundation for
Medical Research.
Vol. 58, No. 17, 2011
ISSN 0735-1097/$36.00
doi:10.1016/j.jacc.2011.07.028
that year, still received excellent care: 91% received all
guideline-recommended interventions for which they were
eligible, and discharge prescription rates were 97% for
aspirin, 96% for beta-blockers, 92% for angiotensinconverting enzyme inhibitors or angiotensin receptor blockers in those with systolic dysfunction, and 89% for lipidlowering drugs in those with elevated levels of low-density
lipoprotein cholesterol. In fact, the care provided to the
high-risk tertile in 2008 was substantially better than the
care received by patients in lower risk tertiles in earlier years
of the study. The rising tide in quality of care in the
GWTG-CAD over the past decade lifted all boats—the
adjusted composite performance measure improved each
year by 30% to 33% in the low-, intermediate-, and
high-risk tertiles. Importantly, the observed improvements
in quality of care over time were due to numerator enhancement (i.e., increased treatment of eligible patients) rather
than denominator minimization (i.e., increased exclusion of
patients due to more rigorous recording of contraindications).
The risk–treatment paradox has been attributed to gaps
in the evidence base (i.e., uncertainty about the risk:benefit
ratio in patients at higher risk who are generally underrepresented in randomized trials) and/or information gaps
inherent in administrative datasets (i.e., lack of data on
confounding clinical and functional variables that the clinician must weigh in making clinical decisions but which are
not captured in administrative databases). Echoing a recent
report from the GWTG–Heart Failure program (2), Motivala et al. (1) found that higher risk patients did have a
greater prevalence of contraindications to many guidelinerecommended therapies but that the risk–treatment paradox
was still present even when the analyses were restricted to
only eligible patients and even when adjustment was made
for multiple clinical covariates not typically captured in
administrative datasets (e.g., body mass index, smoking
status, heart rate, blood pressure, laboratory values).
Thus, other factors must be driving the persistence of the
risk–treatment paradox in myocardial infarction. As clinicians, we tend to be risk-averse, and errors of omission (e.g.,
not prescribing a preventive therapy) are easier to accept
than errors of commission (e.g., prescribing a medication
that then causes an adverse effect in a patient), especially in
patients whom we perceive to have a poor prognosis. Thus,
it is not surprising that an analysis of Medicare data revealed
that utilization of cardiac catheterization in elderly patients
with acute myocardial infarction was more closely correlated
with markers of potential harm (i.e., patients’ bleeding risk
and number of comorbidities) than with potential to benefit
(i.e., patients’ baseline risk) (3). This problem is compounded by the fact that as clinicians we underestimate the
potential benefits and overestimate the risks of preventive
therapies for cardiovascular conditions (4,5), especially in
older or sicker patients. Indeed, an analysis from the
Canadian ACS (Acute Coronary Syndromes) II Registry
did confirm that physicians’ subjective risk assessments for
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McAlister
The Risk–Treatment Paradox
JACC Vol. 58, No. 17, 2011
October 18, 2011:1766–7
patients with acute coronary syndromes correlated poorly
with their Thrombolysis In Myocardial Infarction, Platelet
Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin, and Global Registry of Acute
Coronary Events validated risk scores (6). In fact, the
risk–treatment paradox in that dataset was entirely due to
this imperfect risk stratification because treatment intensity
was directly related to the patient risk at baseline as
perceived by the treating physician. Wider availability of
risk prediction models that permit physicians to accurately
calibrate the potential long-term benefits and risks from
preventive therapies will be a key step in ultimately eliminating the risk–treatment paradox for CAD and other
cardiovascular conditions.
Although the risk–treatment paradox as it is currently
defined is likely to continue to shrink over time as quality of
care improves for patients across the spectrum of risk, I have
one reservation with the current definition. Namely, all
studies of the risk–treatment paradox thus far have focused
on the underutilization of evidence-based therapies in atrisk individuals. However, the other side of the quality coin
is the overutilization of nonevidence-based therapies. Additional studies should examine to what extent overutilization differs across patient risk strata. It has been estimated
that nearly one-quarter of outpatient prescriptions in the
United States were for “off-label” indications (i.e., not
supported by randomized trial evidence or guideline recommendations) (7). Similar off-label utilization rates have also
been reported for cardiac devices such as implantable
cardioverter-defibrillator, cardiac resynchronization therapy,
drug-eluting stents, and percutaneous coronary interventions (8 –11). Of course, off-label use is not necessarily
inappropriate; skilled clinicians often use clinical judgment
in extrapolating beyond the limits of the randomized trial
data for individual patients, and what is considered off-label
in 2011 may become an on-label indication in subsequent
years as the evidence base evolves.
In conclusion, although the rising tide of quality appears
to be attenuating the risk–treatment paradox in acute
myocardial infarction, there are multiple other areas in
cardiology (and other fields of medicine) in which gaps in
1767
care are still sufficiently large (12) that the risk–treatment
paradox remains an important issue for clinicians and
purveyors/consumers of comparative effectiveness research.
It is premature to declare the end of the risk–treatment
paradox.
Reprint requests and correspondence: Dr. Finlay A. McAlister,
2F1.21 WMC, University of Alberta Hospital, 8440 112 Street,
Edmonton, Alberta T6G 2R7, Canada. E-mail: Finlay.McAlister@
ualberta.ca.
REFERENCES
1. Motivala AA, Cannon CP, Srinivas VS, et al. Changes in myocardial
infarction guideline adherence as a function of patient risk: an end to
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failure. Gaps in evidence or quality? Circ Cardiovasc Qual Outcomes
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3. Ko DT, Ross JS, Wang Y, Krumholz HM. Determinants of cardiac
catheterization use in older Medicare patients with acute myocardial
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4. Bungard TJ, Ghali WA, McAlister FA, et al. Physicians’ perceptions
of the benefits and risks of warfarin for patients with non-valvular
atrial fibrillation. CMAJ. 2001;165:301–2.
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6. Yan AT, Yan RT, Huynh T, et al. Understanding physicians’ risk
stratification of acute coronary syndromes. Insights from the Canadian
ACS 2 Registry. Arch Intern Med 2009;169:372– 8.
7. Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among
office-based physicians. Arch Intern Med 2006;166:1021– 6.
8. Al-Khatib SM, Hellkamp A, Curtis J, et al. Non-evidence-based ICD
implantations in the United States. JAMA 2011;305:43–9.
9. Lenfant C. Clinical research to clinical practice—lost in translation?
N Engl J Med 2003;349:868 –74.
10. Ko DT, Chiu M, Guo H, et al. Safety and effectiveness of drug-eluting
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J Am Coll Cardiol 2009;53:1773– 82.
11. Piccini JP, Hernandez AF, Dai D, et al. Use of cardiac resynchronization therapy in patients hospitalized with heart failure. Circulation
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Key Words: guideline adherence y myocardial infarction y paradox y
risk y trends.
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The End of the RiskTreatment Paradox?: A Rising Tide Lifts All Boats
Finlay A. McAlister
J. Am. Coll. Cardiol. 2011;58;1766-1767
doi:10.1016/j.jacc.2011.07.028
This information is current as of October 10, 2011
Updated Information
& Services
including high-resolution figures, can be found at:
http://content.onlinejacc.org/cgi/content/full/58/17/1766
References
This article cites 12 articles, 11 of which you can access for
free at:
http://content.onlinejacc.org/cgi/content/full/58/17/1766#BIB
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