BMJ 2015;351:h5153 doi: 10.1136/bmj.
h5153 (Published 20 October 2015)
Clinical Review
Acute coronary syndromes
Adam Timmis professor of clinical cardiology
NIHR Biomedical Research Unit, Barts Heart Centre, London EC1A 7BE, UK
Acute coronary syndromes, or heart attacks, include unstable
angina and acute myocardial infarction. The latter is further
classified according to electrocardiographic changes as non-ST
elevation myocardial infarction (NSTEMI) and ST elevation
myocardial infarction (STEMI), which comprise 61% and 39%,
respectively, of admissions for acute myocardial infarction
recorded in the UK national registry.1 In most developed
countries incidence rates of acute coronary syndrome are
diminishing; a recent UK study using linked hospital and
mortality data reported 33% and 31% reductions in rates for
adults in 2010 compared with 2002.2 Similar reductions have
been reported from Denmark.3 Another registry based study
from the United States found that the reduction was largely
confined to ST elevation myocardial infarction, whereas rates
of non-ST elevation myocardial infarction have tended to
increase.4 Yet, despite parallel reductions in 30 day case fatality
rates, the British Heart Foundation reports that acute coronary
syndromes remain one of the major causes of premature death
in men and women in the UK.5 This review will provide a
comprehensive account of the pathophysiology, clinical
presentation, management, and outcomes of acute coronary
syndrome, designed to update clinicians involved in caring for
patients with this potentially lethal medical emergency.
What causes acute coronary syndrome?
Acute coronary syndromes are triggered by fissuring or rupture
of an atheromatous plaque in the coronary arterial wall (fig 1).
This stimulates a thrombotic response causing variable
obstruction to flow in the coronary arterial lumen with
downstream ischaemic myocardial injury. In unstable angina
and non-ST elevation myocardial infarction the obstruction to
flow is typically incomplete, whereas in ST elevation myocardial
infarction it is complete.6
What is the definition of acute coronary
syndrome?
The prerequisite for diagnosis of acute myocardial infarction in
the universal definition is the detection of troponin release from
injured cardiac myocytes.7 Diagnosis is confirmed only if this
is associated with chest pain or other criteria listed in box 1.
Increases in troponin levels unassociated with these criteria may
occur in a variety of disorders unrelated to acute myocardial
a.d.timmis@qmul.ac.uk
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Page 1 of 13
CLINICAL REVIEW
infarction, including pulmonary oedema, pulmonary embolism,
cardiac contusion, and aortic dissection.8 Acute myocardial
infarction is most commonly a spontaneous event triggered by
plaque fissuring or rupture (type 1 acute myocardial infarction).
Other types of presentation, such as acute myocardial infarction
due to coronary embolism, coronary angioplasty, or stent
thrombosis, will not be further discussed. In unstable angina,
ischaemia is not severe enough to cause injury to myocytes but
it is now recognised that small increases in troponin levels can
often be detected using high sensitivity assays,9 allowing many
previous diagnoses of unstable angina to be reclassified as
non-ST elevation myocardial infarction. Reclassification
inevitably increases incidence rates of acute myocardial
infarction, but already evidence shows that it favourably
influences decisions about clinical management and outcomes.10
Who gets acute coronary syndrome?
The risk of acute coronary syndrome increases with age and is
greater in men and in people with a family history. However,
other potentially modifiable risk factorssmoking, diabetes,
hypertension, dyslipidaemia, obesity, psychosocial factors, lack
of exercise, and a diet low in fruit and vegetables along with
little or no alcohol consumptionaccounted for more than 90%
of the population attributable risk in the case-control
INTERHEART study across 52 countries.11 This identifies acute
myocardial infarction as a preventable disorder, and a recent
review of the declines in coronary mortality over the past 50
years concluded that the contribution of lifestyle modification
was approximately equal to that of drug and interventional
cardiovascular treatments.12
How does it present?
Clinical experience backed up by observational data show that
the clinical presentation of acute coronary syndrome is variable,
with trivial symptoms such as minor chest discomfort in some
cases and extreme haemodynamic or arrhythmic collapse in
others.13 Typically, however, presenting features are a reflection
of severe myocardial ischaemia combined with activation of
the autonomic nervous system (table 1).
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BMJ 2015;351:h5153 doi: 10.1136/bmj.h5153 (Published 20 October 2015) Page 2 of 13

CLINICAL REVIEW

The bottom line

In the United Kingdom and most other developed countries, incidence rates of acute coronary syndrome are diminishing, but they
remain a major cause of premature death in adults
Death before reaching hospital occurs in nearly 25% of cases of acute myocardial infarction but can usually be prevented by rapid
access to a defibrillator
Prompt reperfusion therapy in ST elevation myocardial infarction reduces infarct size and helps prevent death from heart failure and
ventricular arrhythmias
Lifestyle modificationparticularly smoking cessationand secondary prevention drugs protect against recurrent acute coronary
syndrome
Adherence to guideline recommendations for treatment with an implantable cardioverter defibrillator protects against sudden arrhythmic
death late after acute coronary syndrome

Sources and selection criteria

We searched PubMed and Google using the terms acute coronary syndromes, acute myocardial infarction, unstable angina, ST
elevation myocardial infarction, and non-ST elevation myocardial infarction. We also carried out additional searches targeted at specific
aspects of acute coronary syndrome. Major sources of information were guidelines published by the American Heart Association, the
European Society of Cardiology, and the National Institute for Health and Care Excellence; randomised trials, meta-analyses, and observational
studies reported in major general medical and clinical cardiovascular journals; and personal experience.

Box 1 Third international definition of acute myocardial infarction

Increase or decrease in troponin levels with at least one value >99th centile of upper reference limit, plus at least one of the following:
Symptoms of ischaemia
New ST segment or T wave changes or new left bundle branch block on electrocardiography
Development of pathological Q waves on electrocardiography
Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality
Identification of an intracoronary thrombus by angiography or at postmortem examination

Is the patient having a heart attack?
Acute myocardial infarction is a medical emergency, with
survival closely related to timely diagnosis and treatment. If
acute myocardial infarction is suspected, the guideline from the
UK National Institute for Health and Care Excellence prioritises
calling the emergency services, which provide access to a
defibrillator during transfer to hospital.14 On arrival in the
emergency department the first requirement is 12 lead
electrocardiography (fig 2). If the electrocardiogram can be
recorded in the ambulance before arrival at hospital it accelerates
triage, with registry data suggesting that this may increase the
rates of reperfusion treatment and reduce 30 day mortality.15
Regional ST segment elevation or new left bundle branch block
makes diagnosis of ST elevation myocardial infarction
sufficiently secure for immediate admission. If the
electrocardiogram is non-diagnostic but the clinical presentation
is with typical cardiac chest pain, then admission is also
required. If the chest pain is atypical and the electrocardiogram
is non-diagnostic, troponin levels will determine the admission
diagnosis and the need for hospital stay. Using conventional
troponin assays, decisions have been based on serial blood
samples drawn on first assessment and again 6-9 hours later. In
patients with chest pain, an increasing or decreasing troponin
level with at least one value above the upper reference limit
confirms acute myocardial infarction.7 The advent of high
sensitivity assays now allows diagnostic thresholds to be set at
much lower levels, improving diagnostic sensitivity at the
expense of specificity, with the potential for earlier rule-out of
acute myocardial infarction.16 This potential has been endorsed
by NICE as a means of accelerating diagnostic pathways and
reducing the pressure on emergency beds.17 Patients with atypical
chest pain and without a diagnostic increase in troponin levels
who are rhythmically and haemodynamically stable should
usually be allowed home; a recent study reported adverse cardiac
events in only 0.2% of such cases.18
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How should patients be managed in the
emergency setting?
The NICE guideline recommends intravenous opioids in
sufficient dosage to relieve chest pain.19 It also recommends an
oral loading dose of aspirin 300 mg based on salutary prognostic
benefits first reported in the ISIS-2 (Second International Study
of Infarct Survival trial), when treatment independently reduced
30 day mortality in acute coronary syndrome, further enhancing
the benefits of reperfusion treatment.20 Oxygen treatment is
unhelpful in patients with preserved arterial oxygen saturations
(94%), and may be harmfula recent randomised trial reported
that it tends to increase early myocardial injury.21 In other
respects, management strategies depend on whether the
presenting electrocardiogram shows regional ST elevation.
ST elevation myocardial infarction
Patients presenting within 12 hours of symptom onset require
emergency reperfusion treatment to restore coronary flow and
minimise irreversible myocardial injury.
Primary percutaneous coronary intervention
Primary percutaneous coronary intervention is the preferred
reperfusion strategy (fig 3); the NICE quality standard22 calls
for it to be performed as soon as possible after hospital arrival
but within 120 minutes of the time when clot busting
fibrinolytic treatment could have been given, any delay being
associated with higher mortality.23 If this cannot be achieved,
fibrinolytic treatmentusing agents such as alteplase or
reteplase that can be given by a bolus intravenous
injectionwith coronary stenting in the next 6-24 hours is an
effective alternative.24 Radial access for primary percutaneous
coronary intervention is associated with fewer bleeding
complications and reduced all cause mortality compared with
femoral access.25 Whether complete revascularisation, with
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BMJ 2015;351:h5153 doi: 10.1136/bmj.h5153 (Published 20 October 2015)
additional stenting of high grade coronary stenoses remote from
the culprit artery, improves outcomes remains the subject of
some debate, despite recent randomised trials that have reported
in favour.26 27 The results of larger trials currently in progress
are awaited.
Antiplatelet treatment
Aspirin loading should be accompanied by a loading dose of a
P2Y12 receptor antagonist before primary percutaneous
coronary intervention (table 2). Clopidogrel has long been the
drug of choice but preference is now being given to prasugrel
and ticagrelor, two antiplatelet agents that are more potent and
more rapidly active than clopidogrel. In separate head to head
trials prasugrel and ticagrelor reduced the hazard of death from
cardiovascular causes, non-fatal myocardial infarction, or
non-fatal stroke by 19% and 16%, compared with
clopidogrel.30 31 However, prasugrel increased the risk of life
threatening and fatal bleeding resulting in net harm to patients
with a history of stroke and was no benefit to patients aged 75
or more. These unwanted bleeding effects were less evident
with ticagrelor. Guidelines have been inconsistent about which
P2Y12 receptor antagonist to choose,32 33 but NICE recommends
ticagrelor, which should now be regarded as the P2Y12 receptor
antagonist of choice in patients with ST elevation myocardial
infarction.19 34 Whichever P2Y12 receptor antagonist is chosen
to accompany aspirin, the guidelines are consistent that dual
antiplatelet treatment should continue for 12 months after
primary percutaneous coronary intervention.
Other antithrombotic treatment
Anticoagulation with heparin is mandatory during primary
percutaneous coronary intervention. The European guideline33
considers that enoxaparin may be preferred over
unfractionated heparin, consistent with the findings of a recent
meta-analysis of randomised trials,35 but NICE expresses no
preference.19 The drug is administered by intravenous bolus
injection: 100 U/kg bodyweight for unfractionated heparin, with
continued treatment titrated against partial thromboplastin time,
and 30 mg for enoxaparin, with 12 hourly subcutaneous
injections of 1 mg/kg bodyweight.
Non-ST elevation myocardial infarction and
unstable angina
Clinical management of non-ST elevation myocardial infarction
is guided by the estimated six month mortality risk using the
GRACE score,36 calculated by entering simple clinical risk
factors into a web based model (fig 4).
All patients should receive a loading dose of aspirin 300 mg
and a P2Y12 receptor antagonist. Again, guidelines are
inconsistent about choice of P2Y12 receptor antagonist,37 38 but
NICE prefers ticagrelor because randomised trials30 31 showed
it works better than other treatments available on the NHS.34
As with other acute coronary syndrome, dual antiplatelet
treatment should continue for 12 months. Anticoagulation with
oral fondaparinux 2.5 mg daily is also recommended in non-ST
elevation myocardial infarction based on trial findings of
comparable cardiovascular outcomes but lower bleeding
complications compared with heparin.39 Fondaparinux is usually
continued until its substitution with heparin during cardiac
catheterisation or until full mobilisation in patients treated
conservatively. The NICE quality standard calls for cardiac
catheterisation in the first 72 hours after hospital admission in
patients with an estimated six month mortality 3.0% or more
by the GRACE score, with a view to coronary revascularisation
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Page 3 of 13
CLINICAL REVIEW
by stenting or bypass surgery.22 Meanwhile, treatment with
glycoprotein IIb/IIIa inhibitors (intravenous eptifibatide or
tirofiban) should be considered if chest pain remains
uncontrolled, when earlier cardiac catheterisation may be
necessary. Effective stabilisation of symptoms often occurs with
these potent platelet inhibitors, but mortality reduction has been
hard to confirm in patients pretreated with aspirin and P2Y12
receptor antagonists.40
What if the patient collapses before
reaching hospital?
Obstructive coronary disease with acute coronary syndrome or
widespread myocardial scarring is causative in perhaps 80% of
cases of out of hospital cardiac arrest, the remainder having
non-ischaemic or non-cardiac causes.41 Acute myocardial
infarction is responsible for most cases and carries a high
mortality; UK data for 2002-10 showed that death before
reaching hospital occurs in nearly 25% of cases, constituting
70% of the total attributable mortality.2 Observational studies
confirm that bystander resuscitation is helpful for reducing
mortality,42 but prompt defibrillation is the intervention of choice
for patients with ventricular tachycardia or fibrillation, with
every minute of delay reducing the chances of survival by an
estimated 7-10%.41 If resuscitation leads to return of spontaneous
circulation, survival depends on haemodynamic and neurological
recovery.43 Primary percutaneous coronary intervention,
regardless of the level of consciousness, is now a guideline
recommendation33 for restoring coronary patency and improving
survival if the electrocardiogram shows ST elevation.43 44 Cardiac
catheterisation is also recommended if acute myocardial
ischaemia is suspected, even if electrocardiographic changes
are non-diagnostic.33 One large observational study reported
survival with neurological recovery in about 80% of patients
with return of spontaneous circulation who had regained
consciousness by the time of hospital admission, but up to 33%
of patients who were delivered to hospital unconscious, despite
the return of spontaneous circulation, also made satisfactory
recoveries.43 Randomised trials have failed to show survival
benefit for systemic cooling strategies using infusions of 4C
normal saline.45
What complications might occur?
Box 2 lists the potential complications of acute coronary
syndrome and how they can be managed.
What plans should be in place before
discharge?
Discharge home after 48-72 hours is safe for patients with
uncomplicated acute myocardial infarction.49 Predischarge
echocardiography is recommended for assessment of left
ventricular function, an ejection fraction of 40% or less
providing indication for an aldosterone inhibitor, such as
eplerenone.50 Meanwhile, secondary prevention aimed at
reducing the risk of recurrent acute coronary syndrome and
coronary death should be initiated or planned.
Lifestyle modification
Patients should be offered cardiac rehabilitation with exercise
training and education about how to quit smoking (box 3), eat
healthily, and lose weight. A recent observational study reported
a mortality reduction of 45% for patients after acute coronary
syndrome attending cardiac rehabilitation,51 although the extent
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BMJ 2015;351:h5153 doi: 10.1136/bmj.h5153 (Published 20 October 2015) Page 4 of 13

CLINICAL REVIEW

Box 2 Symptoms and management of potential complications of acute coronary syndrome

Tachyarrhythmia
Atrial fibrillation is often asymptomatic and self limiting, but if the rate is rapid it may exacerbate ischaemia and predispose to heart
failure
Sustained ventricular tachycardia may cause severe heart failure or cardiac arrest, whereas ventricular fibrillation is the usual cause
of out of hospital death if electrical cardioversion is unavailable
Ventricular tachycardia or ventricular fibrillation late (>24 hours) after the onset of chest pain usually requires an implantable cardioverter
defibrillator to protect against sudden death (see box 4)

Bradycardia
Sinus bradycardia and atrioventricular block may complicate inferior infarction but are self limiting and often asymptomatic
Rate often responds to atropine, and temporary pacing is not usually necessary
When advanced atrioventricular block complicates anterior infarction it always denotes extensive myocardial injury. Severe bradycardia
is inevitable and permanent pacing nearly always required

Heart failure
Reflects extensive myocardial injury and is the usual cause of in-hospital death
Pulmonary oedema causes severe shortness of breath and may progress to cardiogenic shock characterised by hypotension, oliguria,
and variable disorientation
Treatment is with oxygen and loop diuretics, cardiogenic shock requiring additional inotrope infusion plus haemofiltration in the event
of resistance to diuretics46
Evidence that intra-aortic balloon pumping influences outcomes is lacking,47 and experience with left ventricular assist devices is
insufficient to support their use outside of specialist centres48

Other complications
Pericarditismay be confused with recurrent ischaemic pain
Myocardial ruptureoften requires emergency surgery if it involves the interventricular septum or papillary muscle
Postmyocardial infarction syndromecharacterised by relapsing pleuropericarditis and increased levels of inflammatory markers

of bias by hidden confounders remains controversial52 and the
results of an earlier randomised trial were negative.53
Which drugs for secondary prevention?
Guidelines recommend secondary prevention with five classes
of drugs that have each been shown to protect against recurrent
acute coronary syndrome and coronary death in randomised
trials (table 3). These are dual antiplatelet treatments with
aspirin and a P2Y12 receptor antagonist, blockers, angiotensin
converting enzyme (ACE) inhibitors, and statins.56-68 High dose
statins are now recommended (atorvastatin 80 mg daily or
equivalent), and for patients intolerant of ACE inhibitors,
angiotensin receptor blockers are an appropriate alternative.
Evidence for blockers is based on early trials in acute
myocardial infarction showing mortality reductions in patients
randomised to metoprolol, although once daily blockers such
as bisoprolol are now preferred even though the trials have been
in populations with heart failure and not acute myocardial
infarction.69 The survival benefits of blockers after acute
myocardial infarction seem to be undiminished in patients with
chronic obstructive pulmonary disease, a condition that should
no longer be regarded as a contraindication for these drugs.70
Based on assumptions of additive and indefinite efficacy,
international guidelines recommend lifelong treatment, with the
exception of dual antiplatelet treatment, for which treatment is
recommended for 12 months, with continuing aspirin
monotherapy thereafter.
protect against sudden death if implanted on the basis of reduced
left ventricular function alone (ejection fraction <30%).73 These
trials have underpinned NICE recommendations (box 4).74
What is the prognosis after an acute
coronary syndrome?
Comparing 2002 with 2010, UK 30 day case fatality rates for
acute myocardial infarction treated in hospital decreased from
18.5% to 12.2% in men and from 20.0% to 12.5% in women
(fig 5).2 Overall case fatality rates, taking account of out of
hospital deaths, were over twice as high in both sexes but
showed similar temporal declines.
Early mortality is higher for ST elevation myocardial infarction
than for non-ST elevation myocardial infarction, but long term
outcomes are similar or worse for non-ST elevation myocardial
infarction.75 76 Among all patients with acute coronary syndrome,
the major independent determinants of mortality in the GRACE
risk model (fig 4) are age, development (or history) of heart
failure, peripheral vascular disease, systolic blood pressure,
renal function, increased troponin levels, cardiac arrest on
admission, and ST segment deviation.36
We thank Barts NIHR Cardiovascular Biomedical Research Unit, funded
by the National Institute for Health Research, and Liz Clark for reading
and critically reviewing the manuscript.
Competing interests: I have read and understood the BMJ policy on
declaration of interests and declare the following: none.

When should implantable cardioverter Provenance and peer review: Commissioned; externally peer reviewed.

defibrillators be considered?
Randomised trials have shown that among patients with acute
myocardial infarction and impaired left ventricular function
(ejection fraction 35%) who experience ventricular arrhythmias
late (>24 hours) after hospital admission implantable
cardioverter defibrillators reduce the risk of sudden death by
30-55%.71 72 More recently these devices have been shown to
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1 Myocardial Ischaemia National Audit Project. How the NHS cares for patients with heart
attack. Annual Public Report April 2013-March 2014. www.ucl.ac.uk/nicor/nicor-news-
publication/minap-annual-report-2014.
2 Smolina K, Wright FL, Rayner M, et al. Determinants of the decline in mortality from acute
myocardial infarction in England between 2002 and 2010: linked national database study.
BMJ 2012;344:d8059.
3 Alzuhairi KS, Sgaard P, Ravkilde J, Gislason G, Kber L, Torp-Pedersen C. Incidence
and outcome of first myocardial infarction according to gender and age in Denmark over
a 35-year period (1978-2012). Eur Heart J Qual Care Clin Outcomes 2015 (In press).
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BMJ 2015;351:h5153 doi: 10.1136/bmj.h5153 (Published 20 October 2015) Page 5 of 13

CLINICAL REVIEW

Box 3 Smoking and acute myocardial infarction

20% of patients with acute myocardial infarction are current smokers54
Among young patients (60 years), 50% are current smokers54
Only about 33% of smokers quit after acute myocardial infarction54
Smokers who quit reduce their risk of major adverse cardiac events by 40%54
Behavioural counselling for one month or more after discharge increases quit rates by 60%55
Adding nicotine replacement therapy to counselling may further increase smoking cessation rates55

Box 4 Indications for implantable cardioverter defibrillators for secondary prevention after acute myocardial
infarction
Cardiac arrest caused by ventricular tachycardia/ventricular fibrillation more than 24 hours after onset of acute myocardial infarction
Sustained ventricular tachycardia with syncope more than 24 hours after onset of acute myocardial infarction
Left ventricular ejection fraction less than 35% three months after acute myocardial infarction

Questions for future research

How can public information campaigns be refined to deliver reductions in the high rates of prehospital death in patients with acute
coronary syndromes?
Will high sensitivity troponin assays permit the safe rule-out of acute myocardial infarction using a single blood test?
How can the management of patients who are unconscious after cardiac arrest be improved to reduce rates of neurological injury?

Tips for non-specialists

Key strategies for saving lives in patients with acute coronary syndromes:
Provide access to a defibrillator as quickly as possible after the onset of symptoms to prevent death from ventricular arrhythmias
Initiate reperfusion treatment immediately after hospital arrival in patients with ST elevation myocardial infarction to reduce infarct size
and prevent death from cardiogenic shock
Before hospital discharge, offer all patients with acute coronary syndromes the full range of secondary prevention measures including
drugs, lifestyle advice, and referral for cardiac rehabilitation to protect against recurrent cardiovascular events
Seek advice about device treatment for patients with late ventricular arrhythmias >24 hours after presentation, who may benefit from
an implantable cardioverter defibrillator to protect against sudden death after hospital discharge

Additional educational resources

Information for healthcare professionals
British Heart Foundation. Heart statistics (www.bhf.org.uk/research/heart-statistics)most comprehensive and up to date statistics on
the effects, prevention, treatment, costs, and causes of cardiovascular disease in the UK
British Cardiovascular Society. Education (bcs.com)information on a broad range of current education initiatives from the BCS
European Society of Cardiology. Education (escardio.org)selection of educational products such as webinars, online courses, clinical
cases, and guidelines into practice
American Heart Association Professional Education Center (https://learn.heart.org)quality science, evidence based, continuing medical
education for healthcare professionals
Medscape. Acute coronary syndromes (ACS) (www.medscape.org/resource/acs/cme)continuing medical education learning centre

Information for patients

British Heart Foundation (www.bhf.org.uk/publications)100s of free publications, leaflets, DVDs, and more for patients with heart
conditions, their families, and those who want to learn more about healthy living
British Heart Foundation. Heart attackheart health (www.bhf.org.uk/heart-health/conditions/heart-attack)information about heart
attacks, including what one feels like and whether aspirin should be taken by particular patients
NHS Choices. Heart attack (www.nhs.uk/conditions/Heart-attack/Pages/Introduction.aspx)information on this medical emergency,
including a short video
National Heart, Lung, and Blood Institute. What is a heart attack? (www.nhlbi.nih.gov/health/health-topics/topics/heartattack)information
to help the public better understand the facts about heart attacks
Womens Heart Foundation. Heart attack facts (www.womensheart.org/content/heartattack/heart_attack_facts.asp)facts about heart
attacks in women

How patients were involved in the creation of this article

This article was critically reviewed by a patient with a cardiac condition who was experienced in the development of the NICE guideline. She
said: I found this article interesting and easy to follow. By the end of it I felt that I had a much better understanding of the conditions which
make up acute coronary syndromes.

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73 Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients 76 Chan MY, Sun JL, Newby LK, et al. Long-term mortality of patients undergoing cardiac
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different? 1 year outcomes in acute myocardial infarction as defined by the ESC/ACC
BMJ Publishing Group Ltd 2015
definition (the OPERA registry). Eur Heart J 2007;28:1409-17.

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Tables

Table 1| Symptoms and signs of acute myocardial infarction

Symptoms and signs Mechanisms

Severe myocardial ischaemia:
Chest pain Ischaemia
Fourth heart sound Forceful filling of non-compliant left ventricle
Low grade fever Inflammation
Leucocytosis and increased levels of inflammatory markers Inflammation
Increase in troponin levels Leakage of protein from injured cardiac myocytes
Activation of autonomic nervous system:
Tachycardia and sweating Sympathetic activation
Bradycardia, nausea, and vomiting Vagal activation (especially in inferior acute myocardial infarction)

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Table 2| Pharmacology and dosing schedules of P2Y12 receptor antagonists

P2Y12 receptor antagonist Prodrug Platelet inhibition (human studies) Onset of antiplatelet action Dose in acute coronary syndrome
Loading Maintenance
Clopidogrel Yes ~35%28 29 Slow 600 mg 75 mg daily
Prasugrel Yes ~80% 28
Fast 60 mg 10 mg daily
Ticagrelor No ~80%29 Fast 180 mg 90 mg twice daily

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Table 3| Drugs for secondary prevention of acute coronary syndrome

Drugs and dose (reference) Duration of treatment Notes

Aspirin
75 mg once daily20
P2Y12 receptor antagonist
Ticagrelor 90 mg twice daily31
or Prasugrel 10 mg once daily30
or Clopidogrel 75 mg once daily30 31
Statins
Atorvastatin 80 mg once daily67
blockers
Bisoprolol 10 mg once daily69
or Metoprolol 100 mg twice daily57 58
Angiotensin converting enzyme inhibitors
Ramipril 10 mg once daily60
or Lisinopril 10 mg once daily61
Life long In patients with atrial fibrillation requiring warfarin or novel oral anticoagulant, triple
treatment increases the bleeding risk and aspirin is often discontinued after four weeks,
particularly if the risk of bleeding is high. In such cases treatment should continue for life
with a P2Y12 receptor antagonist and warfarin or novel oral anticoagulant
12 months
Life long High dose statins are now recommended for all patients with acute coronary syndrome.
Patients with renal disease may require lower doses
Life long Preference is now given to once daily blockers such as bisoprolol even though the benefits
of these drugs have been shown primarily in populations with heart failure.69 Chronic
obstructive pulmonary disease is not a contraindication for blockers70
Life long If side effects occur, particularly cough, substitute with an angiotensin receptor blocker such
as losartan 50-100 mg daily

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Figures

Fig 1 Pathophysiology and electrocardiographic changes in non-ST elevation myocardial infarction (NSTEMI) and ST
elevation myocardial infarction (STEMI)

Fig 2 Admission decisions with acute chest pain. Based on NICE clinical guideline CG9514

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Fig 3 Arteriograms showing thrombotic occlusion of left anterior descending coronary artery (arrowed) in a patient presenting
with anterior ST elevation myocardial infarction (left), and widely patent stented artery after successful primary percutaneous
intervention (right)

Fig 4 The GRACE (Global Registry of Acute Coronary Events) scoring system

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Fig 5 Age standardised 30 day overall and case fatality rates for admissions to hospital (%) for acute myocardial infarction
by sex, 2002-10, England. Adapted from Smolina et al2

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