J. of Cardiovasc. Trans. Res.

DOI 10.1007/s12265-015-9639-z

America vs Europe and the 2014 Non-ST Elevation Acute

Coronary Syndrome Guidelines
Dimitri C. Cassimatis 1 & Nanette K. Wenger 2

Received: 15 January 2015 / Accepted: 4 June 2015

# Springer Science+Business Media New York 2015

Abstract In August of 2014, the American Heart Association

and American College of Cardiology (AHA/ACC) published
a new guideline for the management of patients with non-STelevation acute coronary syndromes. With similar timing, the
European Association for Cardio-Thoracic Surgery (EACTS)
released new 2014 guidelines on myocardial revascularization, including a brief update on the 2011 European Society
of Cardiology guidelines on the management of acute coronary syndromes in patients presenting without persistent STsegment elevation. We briefly summarize key components of
all three of these guideline publications, highlighting differences and concluding that similarities far outweigh differences in the American vs European approach to a patient with
non-ST-elevation acute coronary syndrome.

elevation acute coronary syndromes^ [1]. The title itself reveals an evolution from the 2007 ACC/AHA guidelines on the
Bmanagement of patients with unstable angina/non-ST elevation myocardial infarction^ [2]. In parallel with the AHA/
ACCs release, the European Society of Cardiology (ESC)
and European Association of Cardio-Thoracic Surgery
(EACTS) released new 2014 guidelines on Bmyocardial revascularization,^ [3] updating the 2011 ESC guidelines on the
Bmanagement of acute coronary syndromes in patients presenting without persistent ST -segment elevation^ [4]. There
are some distinct and some subtle differences between the new
and former guidelines, as well as between the AHA/ACC and
the ESC recommendations.

Keywords Non-ST elevation acute coronary syndrome .

Unstable angina . Guidelines . Ischemia-guided therapy

American Guidelines

In August of 2014, the American Heart Association and

American College of Cardiology (AHA/ACC) published a
new guideline for the Bmanagement of patients with non-ST-

To begin, let us more closely examine the 2014 AHA/ACC

guideline. The writing committee chose to evolve the term
unstable angina/non-ST elevation myocardial infarction
(UA/NSTEMI) to non-ST elevation acute coronary syndrome
(NSTE-ACS) to emphasize the pathophysiologic continuum
between UA and NSTEMI and to reinforce that presentations
may be quite similar between UA and NSTEMI.

Associate Editor Emanuele Barbato oversaw the review of this article

Highlights of the 2014 AHA/ACC Guideline

* Nanette K. Wenger
nwenger@emory.edu

Emory University School of Medicine, Atlanta, GA, USA

Emory Heart and Vascular Center, Emory University School of

Medicine, Atlanta, GA, USA

Introduction

An electrocardiogram should be performed and

interpreted within 10 min for chest pain suggestive of
ACS (class I).
Troponins should be drawn at presentation and again at
36 h (class I) while creatine kinase is of no benefit (class
III no benefit).

J. of Cardiovasc. Trans. Res.

Supplemental oxygen should be administered to patients

with NSTE-ACS with arterial oxygen saturation less than
90 %, respiratory distress, or other high-risk features of
hypoxemia (class I).
Oral beta-blocker should be used but only if no heart
failure symptoms, low-output signs, AV nodal block, active asthma, or increased risk for shock (class I).
High-intensity statin should be started if no contraindication (class I).
For all NSTE-ACS, aspirin should be given 162325 mg
immediately if no allergy and continued indefinitely
(class I).
For NSTE-ACS without percutaneous intervention (PCI),
clopidogrel or ticagrelor should be started and continued
for up to 12 months (class I). It is reasonable to prefer
ticagrelor to clopidogrel in this group (class IIA).
For NSTE-ACS with PCI and stent, clopidogrel,
ticagrelor, or prasugrel (P2Y12 inhibitor) should
be loaded and continued for at least 12 months
(class I). It is reasonable to prefer ticagrelor or
prasugrel over clopidogrel in this group (class
IIA), but avoid prasugrel if high risk of bleeding
or prior stroke (class III for prasugrel if prior stroke
or TIA).
Oral dosing recommendations for P2Y12 medications are
as follows:

Clopidogrel 600 mg load then 75 mg daily

Ticagrelor 180 mg load then 90 mg twice daily
Prasugrel 60 mg load then 10 mg daily

All patients with NSTE-ACS need both antiplatelet

agents and anticoagulation. Anticoagulation should
be stopped after PCI unless there is a compelling
reason to continue it (class I). If PCI is not performed, the duration of anticoagulation varies depending on the medication. Unfractionated heparin
should be continued for 48 h, while enoxaparin and
fondaparinux are recommended for the duration of
the hospitalization.
Use of GP IIB/IIIA inhibitor is recommended (class I) if
PCI is performed without adequate P2Y12 inhibition.
Use of GP IIB/IIIA inhibitor is reasonable (class IIA) if
PCI is performed with high-risk features, even with simultaneous adequate P2Y12 administration.
There are two main strategies: Binvasive^ and Bischemiaguided.^ Invasive strategy is further subdivided into immediate invasive, early invasive, and delayed invasive as
follows:
BImmediate (or urgent) invasive strategy^ (<2 h from
diagnosis until invasive evaluation) is recommended for

refractory angina, hemodynamic instability, and electrical

instability (class I).
Early invasive strategy (invasive evaluation within
24 h) is recommended for stabilized NSTE-ACS
with increased risk for events and no contraindication to invasive testing. Use of clinical risk scores
such as the thrombolysis in myocardial infarction
(TIMI) risk score and global registry of acute coronary events (GRACE) risk model are advocated to
determine clinical risk (class I).
BDelayed invasive strategy^ is defined as invasive
evaluation within 2572 h. It is reasonable for patients with NSTE-ACS who are not at high or intermediate risk (class IIA).
BIschemia-guided therapy^ (formerly termed Bnoninvasive^) is recommended for patients at low risk, especially if negative troponin, female, and ACS clinically
unlikely (use of invasive strategy in such patients is class
III no benefit).
Invasive therapy should be avoided for those in whom
risks outweigh benefits, for example, those with extensive
comorbidities.
Regarding perioperative NSTE-ACS related to noncardiac surgery, patients should receive a goaldirected medical therapy modified within the limitations imposed by their specific surgical procedure
(class I). Management should be directed at the underlying cause (class I). In other words, attention
must be directed to potential non-plaque rupture-related causes for ischemia and infarction, such as
anemia, hypoxia, or severe pain (type II MI).
The choice of PCI vs coronary artery bypass graft
(CABG) surgery is for the most part omitted from these
guidelines, with discussion focusing on how to manage
based on the choice made by the clinician. A reference is
made to ACC/AHA PCI and CABG guidelines [5, 6].
The use of P2Y12 inhibition (loading of clopidogrel,
ticagrelor, or prasugrel) is specifically noted to be only a
relative contraindication to CABG within 5 days. For
stable patients, a 5-day delay after clopidogrel or
ticagrelor is recommended, while a 7-day delay after
prasugrel is recommended.
The new guidelines stress the importance of postACS cardiac rehabilitation referral, clear communications regarding prescriptions for medications/activity/diet, and specific instructions to patients for return to driving, working, and sexual activity (class
I). The recommendation level underscores the importance the writing group placed on these (class
I) but the lack of randomized trial evidence in this
area (evidence level C).

J. of Cardiovasc. Trans. Res.

Comparison of American Guideline in 2014 to Those

from 2007
Differences between the 2014 and 2007 ACC/AHA
guidelines start with the updated title, moving away
from calling unstable angina a separate entity from
NSTEMI in 2007 and grouping both as NSTE-ACS in
2014. A second terminology change was made in regard
to the name of the less-invasive management strategy:
In 2007, it was called the Binitial conservative^ strategy,
and in 2014, this was updated to the Bischemia-guided^
strategy.
The drugs ticagrelor and prasugrel are new for the
2014 guideline and were not available for use and thus
not addressed in 2007. Troponin measurement in 2007
was recommended at presentation and again at 68 h;
this was updated in 2014 to presentation and again at
36 h. Oxygen is no longer recommended routinely for
all patients in 2014, as it was in 2007, but only for
those with arterial oxygen saturation less than 90 %,
respiratory distress, or other high-risk features of
hypoxemia.
In 2007, there was a class IIA recommendation within a non-invasive strategy for enoxaparin or
fondaparinux vs unfractionated heparin (UFH); in
2014, this was replaced by a class I recommendation
that all patients with definite NSTE-ACS receive
anticoagulation in addition to antiplatelet therapy. The
choice of anticoagulants in 2014 includes enoxaparin,
bivalirudin, fondaparinux, and UFH, all class I with
specific guidelines on duration of treatment for each
and how performing PCI affects their use. Also in
2014, a specific IIB recommendation regarding PCI
was added, that it is reasonable to consider multivessel
PCI at time of NSTE-ACS to both culprit and nonculprit lesions. Finally, the format of the newer guidelines is slightly more succinct, seeking to provide as
m u c h i n f o r m a t i o n a s p o s s i b l e in fe w e r w o r d s
referencing rather than duplicating relevant recent
guidelines.

for invasive evaluation and treatment but precisely, as in 2011,

utilize the terminology Burgent invasive^ (<2 h), Bearly
invasive^ (<24 h), and Bdelayed invasive^ (2472 h) vs
Bconservative.^

Summary of the 2014 ESC/EACTS Guidelines

(Regarding NSTE-ACS)

Utilize a conservative strategy in low-risk patients, especially women with negative troponin (class I).
An urgent invasive strategy (<2 h) for very high-risk patients, i.e., those with refractory angina, heart failure,
shock, hemodynamic instability, and electrical instability
(class I).
Early invasive strategy (<24 h) for intermediate to highrisk patients. ESC guidelines utilize a GRACE score
>140 to identify such patients and also mention positive
troponin with typical rise and fall and dynamic ST/T
changes (class I).
Delayed invasive strategy (2472 h) for lowintermediate-risk patients, with a GRACE score <140
but at least one other risk factor such as diabetes, reduced
ejection fraction, recurrent angina, recent PCI, prior coronary artery bypass grafting (CABG), or renal dysfunction (class I).
PCI vs CABG in patients with multivessel disease
or complex lesions should be discussed by a heart
team approach, taking into account clinical status,
comorbidities, lesion characteristics, and SYNTAX
score (class I).
If PCI with stenting is done, use of a newer generation
drug eluting stent (DES) is recommended, with at least
12 months of dual antiplatelet therapy (DAPT) for all
stents (class I).
Although not given a strength of classification, it is stated
that if CABG is done, timing depends on clinical status
and also that patient exposure to DAPT is only a relative
contraindication to early CABG.

European Guidelines
The September 2014 guidelines from the ESC/EACTS on
myocardial revascularization include a short section on
Bnon-ST segment elevation acute coronary syndrome.^ The
focus is primarily on myocardial revascularization, and details
of management are primarily unchanged from the 2011 ESC
guidelines on NSTE-ACS. As with the AHA/ACC guideline,
the ESC/EACTS 2014 guidelines compare timing strategies

Comparison of European Guidelines in 2014

to Those from 2011
The ESC full guidelines on the management of acute
coronary syndromes in patients presenting without
persistent ST segment elevation were published in
2011. The 2014 ESC guidelines update detailed above
is virtually unchanged from the 2011 guidelines but is

J. of Cardiovasc. Trans. Res.

much less detailed than the full guidelines in 2011,

especially regarding treatments not directly related to
revascularization. One notable change is the 2014 recommendation to use newer-generation drug-eluting
stents in all cases.

Key ESC 2011 Guidelines, Highlighting Those

That Contrast AHA/ACC

For all NSTE-ACS, load aspirin 150300 mg and maintain 75100 mg daily (class I).
The ESC gives a strong recommendation for ticagrelor or
prasugrel over clopidogrel:
Ticagrelor is favored for all patients at increased risk (e.g.,
positive troponin likely from ACS), even if this means
changing from clopidogrel (class I).
Prasugrel is favored after anatomy is known and
only if patient going for PCI with stent, in a select
group without high risk of bleeding and no prior
stroke, who are P2Y12 inhibitor nave, especially
if diabetic (class I).
Clopidogrel should be used if patient cannot take
ticagrelor or prasugrel (class I).

ESC loading and maintenance dose regimens for P2Y12

inhibitors are comparable to AHA/ACC (see above)
except:
If using clopidogrel after PCI, may consider dose of
150 mg daily for the first 7 days in patients not at high
risk of bleeding (class IIA).

Recommendations for GPIIB/IIIA inhibitor use are

essentially the same as in the AHA/ACC guidelines:
use GP IIB/IIIA inhibitor in high-risk PCI in conjunction with P2Y12 inhibitor or use with PCI and
stenting if no P2Y12 inhibitor was used, but do
NOT use a GPIIB/IIIA inhibitor routinely with
PCI when a P2Y12 inhibitor was already given,
and do not use GP IIB/IIIA inhibitor as part of a
non-invasive strategy.
Recommendations for anticoagulation use are also
similar between the ESC 2011 and AHA/ACC
2014 guidelines: class I recommendation to use
anticoagulation in all NSTE/ACS patients, with specific guidelines on how to manage each medication,
but choice of which one to use left to clinician
(UFH vs enoxaparin vs fondaparinux vs
bivalirudin).
Routine invasive evaluation of the low-risk patient is not
recommended (class III).

Discussion: Comparison of European and American

Guidelines
The major differences between the 2011 ESC NSTEACS guidelines and the 2014 AHA/ACC guideline relate to the stronger recommendation for ticagrelor (or in
select cases, prasugrel) over clopidogrel in the ESC
guidelines and the consideration for higher clopidogrel
dosing in the first week after PCI in the ESC guidelines. The ESC guidelines stress the use of a Bheart
team^ approach to guide revascularization, which is also
discussed but with less emphasis in the text of the
AHA/ACC document. Troponin is recognized as the
key biomarker for myocardial infarction in both guidelines; however, the European guidelines include the use
of a highly sensitive assay that is not yet widely available in America. The recommended dose of aspirin is
slightly different between the two groups: 150300 mg
load and 75100 mg maintenance per ESC, compared to
162325 mg load and 81-325 mg maintenance per
AHA/ACC.
With regard to terminology of timing strategies, the
ESC has been consistent from 2011 to 2014, maintaining the use of the term Bconservative^ for the less invasive strategy, while the AHA/ACC changed the term
to Bischemia guided^ in 2014. To help guide the choice
of timing strategy, the European guidelines recommend
using the GRACE score for risk assessment, while the
American guidelines recommend either the GRACE or
TIMI risk scoring systems. Both European and American guidelines describe in some detail special considerations for women, elderly, and certain comorbidities
such as diabetes and renal failure. Both guidelines share
similar timing strategies, have nearly identical approaches to therapeutic anticoagulation and GP IIB/
IIIA inhibition, and advise against invasive evaluation
of the low-risk patient.

Conclusion
The similarities far outweigh the differences between the 2014
AHA/ACC and 2011 ESC guidelines on the treatment of
NSTE-ACS. The three figures recommended from the guidelines (Figs. 1, 2, and 3) provide excellent summaries of the
treatment strategies outlined in each. The strength with which
the clinician chooses ticagrelor over clopidogrel (one of the
only major differences between the two guidelines based on
required level of evidence for the AHA/ACC version) will
likely increase over time in the USA, but at present, is hindered by the frequent cost difference to the patient, given that
clopidogrel but not ticagrelor is now available in generic form
in the USA. The 2014 AHA/ACC writing group joined their

J. of Cardiovasc. Trans. Res.

Fig. 1 Algorithm for the management of patients with definite or likely NSTE-ACS, reproduced directly from the original 2014 AHA/ACC Guideline [1]

J. of Cardiovasc. Trans. Res.

Fig. 2 Chest pain evaluation algorithms reproduced directly from the original 2011 ESC Guidelines [4]

European colleagues in emphasizing the similar pathophysiology between unstable angina and NSTEMI, by combining
both into the entity of NSTE-ACS. The AHA/ACC guidelines

writing group alone, however, chose to evolve the term

Bconservative strategy^ into Bischemia guided strategy^, to
emphasize that this strategy always includes guideline-based

Fig. 3 Chest pain evaluation algorithms reproduced directly from the original 2011 ESC Guidelines [4]

J. of Cardiovasc. Trans. Res.

medical therapy and may or may not progress to invasive

management based on the individual patients risk for recurrent ischemic events.

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