Comparison of ESC and ACC/AHA guidelines for the diagnosis and management of patients with stable coronary heart disease: Are the differences clinically relevant? An American perspective
Comparison of ESC and ACC/AHA guidelines for the diagnosis and management of patients with stable coronary heart disease: Are the differences clinically relevant? An American perspective
Raymond J. Gibbons 0
0 Reprint requests: Raymond J. Gibbons, MD, Department of Cardiovascular Medicine, Mayo Clinic , 200 First Street, SW, Rochester, MN 55905 , USA
1 Department of Cardiovascular Medicine, Mayo Clinic , Rochester, MN , USA
This issue of the journal features a paper by Joseph
et al.1 which is the latest entry in the series of articles
entitled ‘‘Guidelines in Review’’. This editorial is
intended to provide an American perspective on the
clinically relevant differences between the ESC and
ACC/AHA Guidelines for the diagnosis and
management of patients with stable ischemic heart disease.
Joseph et al have done an excellent job of succinctly
summarizing the many recommendations from these
guidelines that are relevant to imaging in a series of 6
tables and 2 figures, despite the different organizational
structures and wording used by the 2 guidelines to
present recommendations. This editorial will provide my
own personal perspective on the clinically relevant
differences between the 2 guidelines. However, I would
encourage the reader to carefully review the tables and
figures in Joseph et al on their own, as their personal
perspective on what is most relevant to their clinical
practice which may well differ from mine.
Many of the recommendations that appear in the
guidelines for stable coronary artery disease also appear
in separate guidelines for revascularization. The
Guidelines in Review series has already published a
paper on the guidelines for myocardial
revascularization,2 along with two excellent editorials
that provide a European perspective3 and an American
perspective4 on those guidelines. Both of these editorials
include comments about the recommendations for
diagnostic testing, which by necessity overlap with
As previously described,3 the ESC and ACC/AHA
Guidelines satisfy somewhat different needs. The ESC
Guidelines must cover more than 30 different countries
and unique health care systems. Although the US
practice of medicine is certainly not homogeneous, the
overall differences between individual states and regions
in this country are much smaller than the differences in
Europe. The ESC guideline process involves review by
multiple national societies. The ACC/AHA guideline
reviewers are generally more aligned in their perspective
of US medicine. Both guidelines processes involve
evidence review. However, the evidence review process
for the ACC/AHA Guidelines has become much more
rigorous in recent years, as there is now a separate
systematic evidence review committee that examines
key questions for each guideline. This independent
process was instituted by the ACC/AHA in response to
the recommendations from two separate Institute of
Medicine committees—one focused on trustworthiness
of clinical practice guidelines; the other, focused on
systematic evidence reviews. The ACC/AHA Guideline
Task Force carefully reviewed all of these
recommendations and modified the ACC/AHA process.5
I will consider the tables that appear in Joseph et al,
beginning with Table 1 (and Figure 1) regarding stress
testing for diagnosis.
There are several clinically relevant differences
between the guidelines in this table. The first is the
different ways that the guidelines choose to address
patients with a low pre-test probability. The ESC
Guidelines urge consideration of non-cardiac causes of
chest pain in these patients. In contrast, the ACC/AHA
Guidelines have several class IIb recommendations for
patients with a low pre-test probability who ‘‘require
testing’’. These recommendations reflect the common
practice in the US to perform testing on such patients,
although Bayes’ theorem indicates that such testing is
unlikely to be beneficial. Positive tests will inevitably
occur in such patients, due to the imperfect specificity of
our tests, and are very likely to be ‘‘false-positives’’.
These ‘‘false-positives’’ often lead to further
unnecessary testing, and patient confusion rather than
The second clinically relevant difference between
the guidelines deals with the thresholds for pre-test
probability. The exact thresholds for ‘‘low probability’’
and ‘‘high probability’’ are uncertain. The original
ACC/AHA Guideline on stable angina6 used 10% and
90% thresholds, respectively, for these two categories.
The ESC Guidelines have favored 15% and 85%
thresholds. This relatively minor difference is less
important than how these probabilities are determined.
The ACC/AHA Guidelines have favored the early
estimates of Diamond and Forrester,7 modified by the
influence of risk factors(particularly, diabetes mellitus).8
However, in recent years, a consortium of European
centers9 have suggested an important revision of these
estimates, which is incorporated in the ESC Guidelines.
This European formulation reclassifies many patients; in
particular, very few women have a high pre-test
probability. This change likely reflects a number of influences,
including the declining overall population prevalence of
hypertension, hyperlipidemia, and tobacco use.10
The third clinically relevant difference between the
guidelines with respect to diagnosis is the specific Class
III recommendation in the ACC/AHA Guidelines
regarding the use of pharmacologic stress testing in
patients who are able to exercise. Although both
guidelines recommend exercise as the preferred stress
modality in patients who can exercise, the inclusion of
this Class III recommendation in the ACC/AHA
Guidelines reflect a general impression that
pharmacologic stress testing is often used in the United States in
patients who are able to exercise, as clinicians find it too
difficult to take the time to estimate the patient’s ability
to exercise. This unfortunate trend in clinical practice
merits this Class III recommendation.
Table 2 describes the use of CCTA and the
diagnosis of coronary artery disease. There are two clinically
relevant differences. In the ESC Guidelines, CCTA is
given a Class IIa recommendation for diagnosis as an
alternative to stress imaging in patients with
low-intermediate pre-test probability. The ACC/AHA Guidelines
give a similar Class IIa recommendation if the patient is
unable to exercise, but only give a Class IIb
recommendation if the patient is able to exercise. This is not a
minor difference, as many patients are able to exercise.
It reflects a concern at the time the ACC/AHA
Guidelines were developed that there was early evidence in the
United States that the performance of CCTA led to an
increased rate of invasive angiography and subsequent
revascularization.11 That early evidence has been
confirmed subsequently in the PROMISE Trial.12 Both the
PROMISE and SCOT-HEART Trials13 were published
after these ESC and ACC/AHA Guidelines were
developed. It will be interesting to observe the
subsequent changes that are made in these guidelines in
response to the publication of these two trials. It is worth
noting that the different results in the two trials reflect a
difference in behavior of physicians in the United
Kingdom and in that United States in response to
abnormalities detected by CCTA.
The second clinically relevant difference regarding
CCTA for diagnosis is the inclusion of two separate
Class IIb recommendations in the ACC/AHA Guidelines
regarding the use of calcium scoring. These
recommendations reflect the use of calcium scoring by some
clinicians for decision making in symptomatic patients,
even though the evidence supporting that use was very
limited at the time these guidelines were developed.
This is another area where there is now more current
evidence, including a publication from the PROMISE
Trial.14 The ACC/AHA Guideline process will need to
consider this new evidence, and decide whether to
modify its recommendations and text based on these
Table 3 describes the use of stress testing and
CCTA for risk stratification. The recommendations for
CCTA are more detailed in the ACC/AHA document.
Rather than the broad Class IIa recommendation
assigned in the ESC Guidelines, the ACC/AHA
Guidelines identify 2 categories of patients for whom CCTA
has a weaker IIb recommendation – those who can
exercise but have an interpretable ECG, those who
cannot undergo stress imaging, and as an alternative to
invasive coronary angiography when functional testing
indicates moderate to high risk of cardiac events. These
Class IIb recommendations reflect the concern described
previously that CCTA in the US has led to an increased
rate of invasive angiography and subsequent
revascularization. Subsequent revisions of both the ESC and
ACC/AHA Guidelines will reflect the new evidence
from the PROMISE and SCOT-HEART Trials on this
One of the most relevant differences between the
ESC and ACC/AHA Guidelines for risk stratification is
not obvious from review of Table 3, i.e., how to
interpret the results of a stress test to decide that early
invasive angiography and/or revascularization is
warranted. The ESC Guidelines emphasize the identification
of [ 10% ischemia by stress imaging, but misinterpret
the available evidence for SPECT imaging. As detailed
in a 2015 review,15 the ESC Guidelines focus only on
the extent of ischemia, rather than the extent and
severity of ischemia, which was the focus of previous
SPECT studies. The ACC/AHA Guidelines do not make
this error. However, they do not provide clear guidance
for interpretation of the exercise ECG. The ACC/AHA
Guidelines include a figure from the landmark paper by
Lauer,16 but refer to high-risk criteria that are based on
ST segment change and chest pain, components of the
Duke treadmill score17 which were not found to be
significant in the thorough (both retrospective and
prospective) analysis by Lauer.
Table 4 describes the use of stress testing and/or
CCTA for re-assessment of patients during follow-up.
The most clinically relevant difference in this table with
respect to follow-up testing in symptomatic patients is a
Class IIb recommendation for the use of CCTA in the
ACC/AHA Guideline. This recommendation
presumably reflects a desire to ‘‘specify boundaries’’ for the use
of CCTA to avoid its overuse and any downstream
increase in invasive coronary angiography and
With respect to asymptomatic patients or patients
with stable symptoms, the ESC Guidelines include a
Class IIb recommendation for re-assessment in
asymptomatic patients after the ‘‘warranty period’’ has
expired. In contrast, the ACC/AHA recommendations
include a stronger Class III recommendation against
stress imaging or CCTA at follow-up intervals of less
than 5 years post-CABG or 2-years post PCI. This
clinically relevant difference reflects the single
published study regarding the use of the warranty period by
US clinicians18 which found that follow-up testing was
frequently performed before the expiration of the
warranty period in patients without known coronary artery
disease, and well after the expiration of the warranty
period in patients with known coronary artery disease.
This published experience suggests that US clinicians do
not properly apply the warranty period concept.
Table 5, which addresses recommendations for the
use of resting echocardiography, demonstrates clinically
relevant differences between the ESC and the ACC/
AHA Guidelines. The ESC Guidelines list a broad Class
I recommendation for echocardiography. The ACC/
AHA Guidelines restrict the Class I recommendation to
patients with ECG Q waves, a history of prior
myocardial infarction, symptoms or signs of heart failure,
complex ventricular arrhythmias, or an undiagnosed
heart murmur. The ACC/AHA Guidelines include a
weaker Class IIb recommendation for patients with
hypertension or diabetes and an abnormal ECG. The
more restrictive ACC/AHA recommendation is founded
on strong evidence, as multiple previous studies have
shown a very low yield for the assessment of left
ventricular function in patients with a normal resting ECG.
The earlier studies on this subject, summarized in the
original 1998 ACC/AHA Stable Angina Guideline,6
employed a variety of modalities—first-pass
radionuclide angiography, gated radionuclide angiography,
echocardiography, and contrast ventriculography.
Regardless of the imaging method, patients with a
normal ECG had a [ 95% prevalence of normal left
ventricular function. To avoid unnecessary imaging, a
Class III recommendation for patients with a normal
ECG and no other indication for echocardiography has
been a consistent feature of the ACC/AHA Guidelines.
Two recent studies examined the compliance over a
five year period with this Class III recommendation in
both local patients and referral patients.19,20 The findings
in the two studies were remarkably consistent. Among
patients with chest pain and a normal resting ECG,
relatively few patients had an echocardiogram in the
absence of other indications. In those who did, the rate
of abnormal findings was remarkably low and had little
impact on clinical management. In a few patients,
abnormal findings on the resting echocardiogram
performed in violation of the Class III recommendation led
to additional testing using other modalities which failed
to confirm the abnormal echocardiographic finding.
Thus, two recent contemporary studies have reaffirmed
the value of the original long-standing Class III
recommendation in the ACC/AHA Guidelines.
Table 6 describes the investigation of patients with
suspected microvascular or vasospastic angina. The ESC
Guidelines have a number of recommendations; the
ACC/AHA Guidelines do not have any
recommendations for these patients. These differences are certainly
clinically relevant. However, the true prevalence of
these disorders in general patient populations is not
known, as the published data is restricted to a limited
number of academic medical centers with a specific
interest in such patients. For microvascular angina, the
ESC Guidelines define a Class IIb recommendation for
‘‘intracoronary acetylcholine adenosine with Doppler
measurements… to assess coronary flow reserve and to
detect vasospasm’’. This time-consuming protocol is not
widely available. The published experience from the
Mayo Clinic is the largest available series of such
patients.21 It comprised 1,552 patients over a 20 year
period. Most of these highly selected patients (about 1.5
patients per week over 20 years) were referred from
outside Mayo after a coronary angiogram failed to
demonstrate obstructive disease. The level of evidence
cited for this recommendation is expert opinion, which
undoubtedly reflects the presence of one of the
recognized international experts in this area on the ESC
Guideline committee. Recognition of the importance of
this issue in the US prompted a 2016 workshop that was
jointly sponsored by the National Institutes of Health,
the ACC and the AHA. Proceedings of that INOCA
workshop were published in 201722 and provide a very
thoughtful review of the published data and the
The ESC Guidelines also include specific
recommendations for the evaluation of patients with suspected
vasospastic angina, including an ECG during angina,
coronary angiography to determine the extent of CAD in
patients with a characteristic clinical pattern, and
intracoronary provocation tests to identify the type of spasm.
All of these recommendations are only supported by
expert opinion. I suspect that the presence of a
recognized international expert on the ESC committee again
played a role in their inclusion in the ESC guidelines. I
doubt that anyone on the ACC/AHA Guideline
committee would dispute the potential value of these steps in
these highly selected patients. Their omission from the
ACC/AHA Guideline likely reflects the absence of
definitive evidence regarding the prevalence of this
disorder and the absence of any randomized trial
evidence demonstrating the efficacy of the commonly used
empirical therapies. The previously cited INOCA
workshop paper had very specific criteria for the
diagnosis of coronary vasospasm, which are rarely met in
clinical practice in the United States.
I hope that this editorial has highlighted some of the
clinical relevant differences that are evident in the
Guidelines in Review paper by Joseph et al. Joseph et al
did an excellent job. Interested clinicians should
carefully review their paper and this editorial with respect to
their own clinical practice. Readers are encouraged to
monitor further revisions in these guidelines, reflecting
the emerging data from the PROMISE and
SCOTHEART Trials, as well as the INOCA workshop.
Dr. Gibbons is a consultant to Astellas Pharmaceuticals,
PeerView Institute, and Medtronic Corporation.
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