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ESC

2013
European guidelines on
the management of
stable coronary artery
disease
Dr Nikko Nugraha

These guidelines should be applied to


patients suspected coronary artery
disease (SCAD)

Stable coronary artery disease


SCAD characterized by episodes of reversible
myocardial demand/supply mismatch, related to
ischaemia or hypoxia, inducible by exercise,
emotion or other stress, or spontaneously
The prevalence 5 to 7% in women aged 4564
years to 1012% in women aged 6584 and 4 to
7% in men aged 4564 years to 1214% in
men aged 6584.
mortality rates 1.2 to 2.4%, incidence of cardiac
death between 0.6 and 1.4% and of non-fatal
myocardial infarction (MI) : 0.6% and 2.7%.

Symptoms and Signs


The characteristics of discomfort caused by
myocardial ischaemia is usually located in the
chest, near the sternum, but may be felt
anywhere from the epigastrium to the lower jaw
or teeth, between the shoulder blades or in either
arm to the wrist and ngers.
described as pressure, tightness or heaviness;
sometimes strangling, constricting or burning.
The diagnosis and assessment of SCAD involves
clinical evaluation, including biochemical risk
factors and specic cardiac investigations

Non-invasive cardiac
investigations

Three major steps used for


decision-making

Principles of diagnostic
testing

Stress testing for diagnosing


ischaemia
Electrocardiogram exercise testing. The main
diagnostic ECG abnormality during ECG exercise
testing consists of a horizontal or down-sloping STsegment depression 0.1 mV, persisting for at least
0.060.08 s after the J-point, in one or more ECG
leads.
The main value of exercise ECG testing is in patients
with normal resting ECGs.
Inconclusive exercise ECGs are common and in these
patients an alternative non-invasive imaging test often
with pharmacological stress should be selected. In
patients at low intermediate pre-test probability,
coronary CTA is another option.

Stress imaging

Myocardial perfusion scintigraphy (SPECT/PET):


Technetium 99m (99mTc) radiopharmaceuticals
are the most commonly used tracers, employed
with single photon emission computed
tomography (SPECT) in association with a
symptom-limited exercise test on either a
bicycle ergometer or a treadmill
Stress cardiac magnetic resonance: CMR
stress testing, in conjunction with a dobutamine
infusion, can be used to detect wall motion
abnormalities induced by ischaemia

Non-invasive techniques to
assess coronary anatomy
Computed tomography. Calcium scoring (without
contrast injection) has no role in symptomatic
patients for diagnosing or excluding coronary
stenosis.
high Agatston score >400, not to proceed with
coronary CTA if the calcium score exceeds 400
Magnetic resonance coronary angiography. This
technique is primarily a research tool.
Because of its simplicity and widespread availability,
treadmill or bicycle exercise testing, using 12-lead
ECG monitoring, remains a useful option

Initial diagnostic management of patients with


suspected SCAD

Invasive coronary angiography

Stratication for risk of


events

Non-invasive testing in suspected SCAD with


intermediate TPT

Stratication for risk of


events

Vasospastic Angina
Patients with microvascular angina have angina with mostly
typical features although the duration of symptoms may be
prolonged and relation to exercise is somewhat inconsistent.
Often, these patients have abnormal results of stress tests.
Patients with vasospastic angina present with typically
located anginal pain, which occurs at rest but does notor
occurs only occasionallywith exertion (typically at night and
in the early morning hours). The ECG during vasospasm is
classically described as showing ST-elevation. Nitrates usually
relieve the pain within minutes. Angiographically, these
patients may show focal occlusive spasm (Prinzmetal's angina
or variant angina)

Lifestyle and pharmacological


management
The aim of the management of SCAD is to
reduce symptoms and improve prognosis.
The management of CAD patients are
lifestyle modication, control of CAD risk
factors, evidence-based pharmacological
therapy and patient education.
Lifestyle recommendations include smoking
ces- sation, healthy diet, regular physical
activity, weight and lipid management, BP
and glucose control.

Regular physical activity is associated with a decrease


in CV morbidity and mortality in patients with CAD.
Exercise training should be advocated to improve
exercise capacity and reduce myocardial oxygen
consumption.
Sexual activity is associated with an exercise workload
of up to 6 METS. Pharmacological therapy with
phosphodiesterase type 5 (PDES) inhibitors (sildenal,
tadalal and vardenal) are effective, safe and well
tolerated in men with stable CAD.
Hormone replacement therapy is at present not
recommended for primary or secondary prevention of
CVD.

Pharmacological management
of SCAD
To obtain relief of angina symptoms the guidelines
advise:
Short-acting nitrates to provide immediate relief of angina
symptoms.
Lifestyle changes, regular exercise training and patient
education.
To prevent the occurrence of cardiovascular events
the guidelines advise:
To reduce the incidence of acute thrombotic events and the
development of ventricular dysfunction by
pharmacological or lifestyle interventions.
A combined pharmacological and revascularization strategy
in patients with severe lesions in coronary arteries

Medical management of patients


with SCAD


Anti-ischaemic drugs
Nitrates offer coronary arteriolar and venous
vasodilatation, and by the reduction of preload. For
acute effort angina short-acting nitrates as sublingual
nitroglycerin is the standard initial therapy.
In post-MI patient b-blockers achieved a 30% risk
reduction for CV death and MI. b-blockers may be the
rst line anti- anginal therapy in stable CAD patients
without contraindica- tions.
Calcium channel blockers reduce the peripheral
vascular resistance. Group of non-dihydropyridine ,
verapamil has a large range of approved indications,
including all varieties of angina

Nicorandil is a nitrate derivative of nicotinamide may be added


after b-blockers and CCBs. Long-term use of oral nicorandil may
stabilize coronary plaques. Occasional side- effects include oral,
intestinal and perianal ulceration.
Trimetazidine is an anti-ischaemic metabolic modulator.
Trimetazidine added to beta-blockade improved effort-in- duced
myocardial ischaemia.
Ranolazine is a selective inhibitor of late sodium channel current
with anti-ischaemic and metabolic properties. Rano- lazine prolongs
QTc.
Allopurinol, an inhibitor of xanthine oxidase reduces vascular
oxidative stress.
Molsidomine as a direct NO donor has anti-ischaemic effects similar
to those of isosorbide dinitrate.
Patients with low blood pressure or low heart rate should be started
at very low doses, with preferential use of drugs with no- or limited
impact on BP, HR, such as ivabradine (in patients with sinus rhythm),
ranolazine or trimetazidine.

Event prevention
Antiplatelet in prevention of ischaemic events and
aspirin is the drug of choice. The use of antiplatelet
agents is associated with a higher bleeding risk.
Clopidogrel is a second-line treatment for aspirinintolerant CVD patients.
Prasugrel and ticagrelor are new P2Y12 antagonists that
achieve greater platelet inhibition, compared with
clopidogrel.
Dual antiplatelet therapy combining aspirin and a
thienopyridine is the standard of care for patients with
ACS
Platelet function testing in SCAD patients undergoing PCI
is not recommended as a routine.

SCAD patients should be treated with statin with a target of LDL-C <
1.8 mmol/l and/or >50% reduction
ACE inhibitors reduce total mortality, MI stroke and heart failure in
patients with co-existing hypertension, LVEF 40%, diabetes or
CKD. ARB treatment may be an alternative when ACE is not
tolerated.
Aldosterone blockade with spironolactone or eplerenone is
recommended in post-MI patients without signicant renal
dysfunction or hyperkalaemia, who are already receiving therapeutic
doses of an ACE inhibitor and a b-blocker, have an LVEF 40% and
have either diabetes or heart failure.
It is recommended in the rst line a b-blocker or a CCB to a shortacting nitrate.

New ESC guidelines and


Ivabradine
Adding ivabradine 7.5 mg twice daily to atenolol therapy gave better control of heart rate and
anginal symptoms.
In 1507 patients with prior angina enrolled in the Morbidity-Mortality Evaluation of the If Inhibitor
Ivabradine in Patients With Coronary Artery Disease and Left Ventricular Dysfunction
(BEAUTIFUL) trial, ivabradine reduced the composite primary end point of CV death,
hospitalization with MI and HF, and reduced hospitalization for MI. The effect was
predominant in patients with a heart rate 70 bpm.
Ivabradine is thus an effective anti-anginal agent, alone or in combination with -blockers.

Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery
disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949-3003.

New ESC guidelines and


Trimetazidine
Trimetazidine is an anti-ischemic metabolic modulator, with similar antianginal efficacy to propranolol in doses of 20 mg thrice daily.
Trimetazidine (35 mg twice daily) added to -blockade (atenolol)
improved effort-induced myocardial ischemia, as reviewed by the EMA in
June 2012.
In diabetic persons, Trimetazidine improved HbA1c and glycemia, while
increasing forearm glucose uptake.

Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery
disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949-3003.

Revascularization
Bare metal stents (BMS) are associated with a
2030% rate of angiographic stenosis within 69
months after implantation.
Drug-eluting stents (DES) reduce the incidence
of restenosis and ischaemia-driven repeat
revascularization.
Coronary artery bypass surgery
When technically feasible, with an acceptable
level of risk and a good life expectancy,
revascularization is indicated in chronic
angina refractory to OMT

Revascularization Procedure

Specic patient proles


Women
Women more frequently have CAD with stable angina and no
obstructive coronary disease.
Women are more likely to have complications from revascularization.

Diabetic patients
Need different risk factor management.

Older patients
High-risk group with higher mortality and higher rates of myocardial
infarction.
Usually undertreated, receiving less drugs.
Difficult diagnosis due to atypical symptoms.
Higher risk of complications during and after coronary revascularization.

Comorbidities/intolerance
Depending on comorbidities/tolerance, it is indicated to use second-line
therapies as rst-line treatment in selected patients.

Conclusion
ESC Guidelines highlighted two aims for the pharmacological management
of stable CAD patients: obtain relief of symptoms and prevent cardiovascular
events.
CAD patients should all receive aspirin and a statin, plus an ACE inhibitor
in case of comorbidities.
-blockers or CCBs should be prescribed as first-line treatment to reduce
angina.
Ivabradine and Trimetazidine (as well as long-acting nitrates, nicorandil and
ranolazine) are recommended second-line, in combination with first-line
treatment, in patients remaining symptomatic.
Physicians should consider
revascularization procedures.

optimal

medical

treatment

before

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