JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
17, 2017
2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER
EDITORIAL COMMENT
On the Stability of
Stable Coronary Artery Disease*
Jos A. Barrabs, MD, Bruno Garca del Blanco, MD, David Garcia-Dorado, MD
S table coronary artery disease (CAD) remains a
major public health burden worldwide. It is
estimated that 6.3% of US adults $20 years
of age have some form of CAD. The prevalence of
myocardial infarction (MI) in this age group is
3.0% and the prevalence of angina is 3.4%, with
signicantly higher percentages among the elderly
(1). Treatment of patients who have stable CAD in-
cludes lifestyle modications, control of CAD risk
factors, use of antithrombotic agents and other
drugs that have been shown to reduce ischemic
adverse events, antianginal therapies if needed,
and revascularization in patients with poorly
controlled symptoms or with high-risk features on
noninvasive testing.
At the present time, risk stratication in patients
with stable CAD is becoming particularly important,
given the current possibility of individualizing the
intensity of secondary prevention therapies aimed at
inhibiting thrombosis or reducing blood cholesterol
levels (25) and the existence of data supporting
prolongation of dual antiplatelet therapy after stent
implantation in patients at higher risk of thrombotic
events (6,7). However, there is relatively little
information on the prognosis and predictors of
ischemic adverse events in patients with stable CAD
*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 Servicio de Cardiologa, Hospital Universitari Vall dHebron,
Universitat Autnoma de Barcelona, Barcelona, Spain. The authors
research is supported by Instituto de Salud Carlos III, Spain (PI12/01844,
PI16/00232, PI14/01431, and CIBER-CV), co-nanced by the European
Regional Development Fund. Dr. Barrabs has received funding from
AstraZeneca and Menarini for educational activities. Dr. Garcia del Blanco
has received funding from Edwards Lifesciences and Medtronic for
educational activities. Dr. Garcia-Dorado is a consultant to Neurovive
Pharmaceutical.
VOL. 69, NO.
ISSN 0735-1097/$36.00
http://dx.doi.org/10.1016/j.jacc.2017.03.535
managed according to contemporary standards of
care. Studies addressing these issues are relatively
old and/or included patients with recent acute
events (810). The recent PEGASUS-TIMI 54 (Pre-
vention of Cardiovascular Events in Patients with
Prior Heart Attack Using Ticagrelor Compared to
Placebo on a Background of AspirinThrombolysis In
Myocardial Infarction 54) trial included patients
with MI 1 to 3 years before enrollment with some
additional high-risk features (2). In the control arm
of the study (n 7,067), the incidence of
cardiovascular death, MI, or stroke increased
linearly, up to 9.04% at 3 years. In the multinational
REACH (Reduction of Atherothrombosis for
Continued Health) registry, the 4-year rate of the
same combined endpoint in 15,264 outpatients with
stable atherosclerosis but no previous ischemic
events was 12.2%, and in 21,890 patients with
previous ischemic events (no mention of exclusion
of patients with recent events), it was 18.3% (11).
SEE PAGE 2149
In this issue of the Journal, Lemesle et al. (12)
report on the incidence, predictors, and prognosis
of MI in 4,094 patients with stable CAD (no MI or
coronary revascularization in the previous year)
enrolled between 2010 and 2011 in the French
CORONOR (Follow-up of a cohort of stable coronary
patients in Nord-pas-de-Calais region) Registry who
had 5-year follow up data (98% of those included). MI
incidence occurred linearly at a rate of 0.8% per year,
and one-third were classied as ST-segment eleva-
tion myocardial (STEMI). Baseline predictors of MI
were active smoking, poorly controlled diabetes
mellitus or hypercholesterolemia, persistent angina,
and multivessel disease, whereas previous coronary
artery bypass surgery was inversely associated with
this complication. Incident MI was associated with an
increased age- and sex-adjusted risk of death. Among
2158 Barrabs et al. JACC VOL. 69, NO. 17, 2017

MI Incidence in Stable CAD MAY 2, 2017:21579

the 2,816 patients with previous stent implantation,
MI was related to very late stent thrombosis (VLST) in
20% (59% of these were STEMI) and occurred at a
nonstented site in 77% (only 26% of these were
STEMI). The risk of death was particularly increased
after VLST-related MI even after adjusting according
to the type of MI. The authors concluded that, in
outpatients with stable CAD, MI incidence occurred
at a stable rate of 0.8% annually, was related to VLST
in one-fth of cases, and was associated with an
increased mortality, especially for VLST. They also
found that multivessel CAD and
uncontrolled risk factors were strongly associated
with MI, whereas previous coronary artery bypass
surgery had a protective effect.
This study is one of the few that has focused on the
risk of ischemic events in patients with truly stable
CAD (12), and the authors are to be commended for
their comprehensive follow-up and analysis. The
study provides data on the contemporary incidence of
MI and VLST in this population and underscores the
importance of adequate risk factor control and the
poor prognosis associated with VLST. Some aspects
should be considered when interpreting the low rates
of MI observed compared with previous studies
(2,8,10,11). First, median times from the last MI or the
last revascularization procedure to inclusion were
5 and 4 years, respectively, and most patients were
free of angina at study entry (13). This nding means
that the results cannot be extrapolated to patients
with more recent events or with persistent symp-
toms. Second, the fact that two-thirds of the stents
implanted were bare metal should not be overlooked
when interpreting the rates of VLST observed. Third,
the study focused on incident MI, but the combined
incidence of sudden death (which we know is caused
by an acute MI in a signicant proportion of cases)
and MI was 50% higher than that of conrmed MI. In
addition, other ischemic endpoints such as ischemic
stroke, which shares pathophysiological features
with MI and can be prevented in part with the same
interventions (2,8), were not considered. Finally, it is
remarkable that one-fth of these patients with very
stable CAD were undergoing dual antiplatelet therapy
at study entry and that this subset had a higher inci-
dence of MI. It would have been interesting to know
whether these patients had a higher baseline risk
prole and whether dual antiplatelet therapy was
continued throughout the follow-up period.
residual Although it was less than optimal, control of CAD
risk factors in this study (12) tended to be better
than that reported previously in similar populations
(11,14), which may partially explain the low rates of
MI observed. Interestingly, the study that reported
MI rates closer to those observed herein also
described a comparable degree of risk factor control
(9). Given this close association between risk factor
control and incident MI, the results underscore the
critical importance of a tight control of residual risk
factors to reduce the incidence of ischemic events
in patients with stable CAD in the long term.
Finally, the study by Lemesle et al. provides some
hints about the subset of stable patients who might
benet from a more potent antithrombotic therapy.
However, more tools to quantify as precisely as
possible the balance between the risks of ischemic
and bleeding complications in patients with stable
CAD are needed, and hopefully will be available
in the near future, to guide clinicians decisions in
this respect.
ADDRESS FOR CORRESPONDENCE: Dr. Jos A.
Barrabs, Servicio de Cardiologa, Hospital Uni-
versitari Vall dHebron, Pg. Vall dHebron 119, 08035
Barcelona, Spain. E-mail: jabarrabes@vhebron.net.

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KEY WORDS myocardial infarction, prognosis,
secondary prevention, stable coronary artery
disease, stent thrombosis
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