Management of Stable Angina Pectoris

CLINICAL PRACTICE GUIDELINES
Date: MOH/
MANAGEMENT OF
STABLE ANGINA PECTORIS
MOH Academy of NHAM

Logo Medicine Logo Logo
Statement of Intent
This clinical practice guidelines (CPG) is meant to be a guide for clinical practice,
based on the best available evidence at the time of development. Adherence to
these guidelines may not necessarily guarantee the best outcome in every case.
Every health care provider is responsible for the management of his/her patient
based on the clinical picture presented by the patient and the management options
available locally.
Period of validity
This CPG was issued in ???? and will be reviewed in 5 years or sooner if
new evidence becomes available.
CPG Secretariat
c/o Health Technology Assessment Unit
Medical Development Division
Ministry of Health Malaysia
4th Floor, Block E1, Parcel E
62590, Putrajaya.
Electronic version available on the following website:
http://www.moh.gov.my
http://www.acadmed.org.my
http://www.malaysianheart.org
ii
MESSAGE FROM DIRECTOR GENERAL OF HEALTH
iii
MEMBERS OF THE EXPERT PANEL
CHAIRPERSON
Dr. Azani Mohd Daud
Consultant Cardiologist
Gleneagles Intan Medical Centre
Wilayah Persekutuan
MEMBERS (In alphabetical order)

Dr. Abd Kahar Ghapar
Hospital Serdang
Selangor
Dr. Betty Teh

Sime Darby Medical Centre
Selangor
Dr. Choo Gim Hooi

KPJ Selangor Specialist Hospital
Selangor
Dr. Haizal Haron Kamar

Tropicana Medical Centre
Selangor
Dr. K. Sree Raman

Senior Consultant Physician
Hospital Tuanku Ja’afar
Seremban
Negeri Sembilan
Dr. Oteh Maskon

University Kebangsaan Malaysia Medical Centre
Wilayah Persekutuan
Dr. Shaiful Azmi Yahaya

Institut Jantung Negara
Wilayah Persekutuan
Dr. Tong Seng Fah

Consultant Family Physician
Department of Family Medicine
University Kebangsaan Malaysia Medical Centre
Wilayah Persekutuan
iv
Wilayah Persekutuan
EXTERNAL REVIEWERS (in alphabetical order)
The following external reviewers provided feedback on the draft.
Dr. Alzamani Mohammad Idrose

Emergency Physician
Hospital Kuala Lumpur
Wilayah Persekutuan
Dr Aris Chandran
Hospital Ipoh
Perak
Basariah Naina
Pharmacist
Hospital Kuala Lumpur
Wilayah Persekutuan
Dr. Chew Boon How

Senior Medical Lecturer,
Department of Family Medicine
Faculty of Medicine and Health Sciences
University Putra Malaysia
Selangor Darul Ehsan
Dr. Kauthaman A. Mahendran

Hospital Melaka
Melaka
Dr. Jeyamalar Rajadurai

Sime Darby Medical Centre
Selangor
Dr. M. Ramalingam
Secretariat Justice of Peace
Negeri Sembilan
Dr. Shaiful Bahari Ismail

Consultant Family Physician
Hospital Universiti Sains Malaysia
Kelantan
Dr. Sim Kui Hian

Sarawak General Hospital
Sarawak
v
Dr. Sulaiman Tamanang
Consultant Radiologist
Prince Court Hospital
Wilayah Persekutuan
Dr. Wan Azman Wan Ahmad

University Medical Malaya Centre
Selangor
Dr. Venugopal Balchand

Consultant Cardiothoracic Surgeon
Institut Jantung Negara
Wilayah Persekutuan
Zaidah Baharuddin
Pharmacist
Serdang Hospital
Wilayah Persekutuan
Dr. Zurkurnai Yusof

Hospital Universiti Sains Malaysia
Kelantan
vi
Rationale and Process of Guideline Development
Rationale
Coronary artery disease (CAD) comprises a broad spectrum of manifestation ranging
from asymptomatic atherosclerosis to stable angina pectoris (SAP), acute coronary
syndrome (ACS), myocardial infarction (MI) and congestive heart failure (CHF). The
management of SAP has not been extensively studied in large randomised clinical
trials.
In Malaysia, these patients may be managed by cardiologists, physicians and primary

care doctors. The CPG on Management of SAP was developed to help guide clinicians
in the management of this group of patients. No previous guideline was available in
Malaysia prior to this.
Process
This CPG was initiated by the National Heart Association of Malaysia (NHAM) in
collaboration with the Academy of Medicine Malaysia (AM) and Ministry of Health
Malaysia (MOH). The guideline committee consisted of cardiologists, physicians and
primary care physician from the government, universities and private hospitals.
This CPG was adapted from the European Society of Cardiology (ESC) Guidelines on
the Management of Stable Angina, 2006. The CPG was evaluated using the Appraisal
of Guidelines for Research and Evaluation (AGREE) prior to adaptation. Further
evidence was evaluated from relevant publications from January 2006 through
December 2009.
Literature search was carried out at the electronic databases of PUBMED/MEDLINE,

Cochrane Databases of Systemic Reviews (CDSR), journal full text via OVID search
engine. Refer to Appendix 3 for the terms used to retrieve articles.
Reference was also made to other guidelines on the management of stable angina
pectoris including The American College of Cardiology (ACC)/American Heart
Association (AHA) 2007 chronic angina focused update of the ACC/AHA 2002
Guidelines for the Management of Patients With Chronic Stable Angina; European
Society of Cardiology (ESC) Guidelines on the Management of Stable Angina, 2006;
ACC/AHA guidelines for the clinical application of echocardiography, 1997; European
guidelines on cardiovascular disease prevention in clinical practice (constituted by
representatives of nine societies and by invited experts), 2007; American Diabetes
Association, Standards of Medical Care in Diabetes, 2008; Implications of recent
clinical trials for the National Cholesterol Education Program Adult Treatment Panel
III guidelines, 2004; ACC/AHA guidelines of percutaneous coronary interventions,
2001. Malaysia CPG on management of Type 2 Diabetes Mellitus, 2009; Malaysia CPG
on Prevention of Cardiovascular Disease in Woman, 2008; Malaysia Consensus
statement from on the utilization of cardiac CT, 2008; Malaysia CPG on Management
of Acute ST Segment Elevation Myocardial Infarction (STEMI), 2007; Malaysia Medical
Nutritional Therapy Guidelines for Hyperlipidaemia and Hypertension, 2005; Malaysia CPG on
Management of Obesity, 2004; Malaysia CPG on Treatment of Tobacco Use and
Dependence, 2003; Malaysia Clinical Practice Guidelines on Dyslipidaemia, 2003;
Malaysia CPG of UA/NSTEMI, 2002; Malaysia CPG on Erectile Dysfunction, 2000;
Malaysia Guidelines for Medical Practitioners performing medical examinations for
vocational licence (PSV and GDL).
vii
In addition, the reference lists of all relevant retrieved articles as well as the
reference list of the other guidelines reviewed were used to identify further studies.
All relevant information was discussed thoroughly over several meetings before a
draft guideline was prepared. The draft was submitted to the Technical Advisory
Committee for Clinical Practice Guidelines, as well as the Health Technology
Assessment (HTA) and Clinical Practice Guidelines Council, MOH Malaysia for review
and approval. This was then submitted to a group of external reviewers selected from
MOH hospitals, academic institutions as well as the private sector.
Objectives
These guidelines are intended to provide education and awareness on ways to:
1. Identify patients with stable angina
2. Assess, risk stratify and manage these patients appropriately
Clinical Questions
The clinical questions addressed in these guidelines include:
1. How does one diagnose a patient with SAP and exclude patient with unstable
angina?
2. Having identified patients with SAP, what appropriate tests should be done for
diagnosis and prognostication?
3. Which patients should be referred for invasive procedures?
4. What appropriate treatment modalities, either non-pharmacological and/or
pharmacological to be utilised?
Target Group
This guideline is directed at all healthcare providers treating SAP – general
practitioners, medical officers, general and family physicians and cardiologists.
Target Population
This guideline is for the management of patients with Stable Angina Pectoris. It
excludes patients with new-onset angina, crescendo angina and rest angina.
Dr. Azani Mohd Daud

Chairperson
viii
GRADES OF RECOMMENDATIONS AND LEVELS OF EVIDENCE
Grades of Recommendation
Conditions for which there is evidence and/or general agreement that
I
a given procedure/therapy is beneficial, useful and/or effective
Conditions for which there is conflicting evidence and/or divergence

II
of opinion about the usefulness/efficacy of a procedure/therapy
IIa Weight of evidence/opinion is in favor of its usefulness/efficacy
IIb Usefulness/efficacy is less well established by evidence/opinion
III Conditions for which there is evidence and/or general agreement that
a procedure/therapy is not useful/effective and in some cases may be
harmful
Levels of Evidence
Data derived from multiple randomised clinical trials or meta
A
analyses
Data derived from a single randomised clinical trial or large non
B
randomised studies
Only consensus of opinions of experts, case studies or standard of
C
care
LEVELS OF EVIDENCE
Adapted from the American Heart Association (AHA) and the European Society of
Cardiology (ESC)
ix
Clinical Evaluation of patients with chest pain
Chest pain
CLINICAL EVALUATION
1. History
2. ECG
3. Basic investigations
Diagnosis
Non anginal chest pain* Suspected stable angina Suspected UA/ACS
Manage accordingly Refer to CPG on

UA/NSTEMI & CPG on
Assessment of ischaemia Management of Acute ST-
1. Stress ECG and or Segment-Elevation
2. Stress imaging Myocardial Infarction
NO ischaemia
(Pharmacological/Exercise) (STEMI) 2007, 2nd edition
Ischaemia
Confirmed stable angina
Evaluate prognosis on basis of clinical evaluation and non-invasive tests

Prognosis
Low risk Intermediate risk High risk
Medical therapy Medical therapy

Medical therapy
± AND
Coronary arteriography Coronary arteriography
*Refer to Table 4
Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of
angina.
x
TABLE OF CONTENT
Statement of intent ii
Message from the Director General of Health iii
Members of expert panel iv
List of external reviewers v
Rationale and process of guidelines development vii
Grades of recommendation and levels of evidence ix
Algorithm for the initial evaluation of patients with clinical symptoms of
x
angina
Table of Content xi
1. INTRODUCTION 1
2. DEFINITION AND PATHOPHYSIOLOGY 2
3. PROGNOSIS 3
4. DIAGNOSIS AND ASSESSMENT 4
4.1 Symptoms and signs 4
4.2 Laboratory tests 5
4.3 Chest radiography (CXR) 6
4.4 Non-invasive cardiac investigations 6
4.4.1 Resting Electrocardiography (ECG) 6
4.4.2 Exercise stress testing 7
4.4.3 Stress testing in combination with imaging 8
4.4.4 Pharmacological stress testing in combination with
9
imaging
4.4.5 Stress Cardiac Magnetic Resonance (CMR) 10
4.4.6 Echocardiography (Echo) at rest 11
4.4.7 Ambulatory ECG monitoring 11
4.5 Non-invasive techniques to assess coronary calcification
11
and coronary anatomy
4.5.1 Electron Beam Computed Tomography (EBCT) 11
4.5.2 Multislice Computed Tomography (MSCT) 12
4.5.3 Cardiac Magnetic Resonance (CMR) 12
4.6 Invasive techniques to assess coronary anatomy 12
4.6.1 Coronary angiography 12
5. RISK STRATIFICATION 13
5.1 Clinical Evaluation 14
5.1.1 Clinical history 14
5.1.2 Physical Examination 14
5.2 Resting ECG 14
5.3 Stress Testing 15
5.3.1 Exercise stress test 15
5.3.2 Stress echocardiography (Echo) 16
5.3.3 Pharmacological stress echocardiography 16
5.3.4 Stress perfusion scintigraphy 17
5.3.5 Stress cardiac magnetic resonance (CMR) 17
5.4 Ventricular function 17
5.5 Coronary arteriography 18
6. TREATMENT 19
6.1 Aim of Treatment 19
6.2 General Management 19
6.2.1 Lifestyle Modification 19
xi
6.2.1.1 Smoking 19
6.2.1.2 Dietary control and fibre intake 21
6.2.1.3 Alcohol restriction 22
6.2.1.4 Physical activity 22
6.2.2 Health Supplements 22
6.2.2.1 Omega-3 fatty acids 22
6.2.2.2 Vitamins, anti-oxidants and other health
22
supplements
6.2.3 Others 23
6.2.3.1 Psychological factors 23
6.2.3.2 Sexual activity 23
6.2.3.3 Employment 23
6.2.3.4 Heavy vehicle driving 24
6.2.4 Hypertension (HPT), Diabetes Mellitus (DM) and
24
other disorder
6.3 Pharmacological Treatment of Stable Angina Pectoris 25
6.3.1 Acute Treatment 25
6.3.2 Long-term Treatment 25
6.3.2.1 Anti-thrombotic agents 25
6.3.2.1.1 Low dose aspirin 25
6.3.2.1.2 Thienopyridines 25
6.3.2.1.3 Other anti-thrombotic agents 26
6.3.2.2 Lipid lowering therapy 26
6.3.2.3 ACE-inhibitors (ACEIs) 27
6.3.2.4 Angiotensin receptor blockers (ARBs) 27
6.3.2.5 Heart rate reducing agents 28
6.3.2.5.1 Beta-blockers 28
6.3.2.5.2 Ivabradine 28
6.3.2.5.3 Non-dihydropyridine calcium channel
29
blockers (CCBs)
6.3.2.6 Calcium channel blockers (CCBs) 29
6.3.2.6.1 Dihydropyridine calcium channel blockers
29
(CCB)
6.3.2.6.2 Non-dihydropyridine calcium channel
29
blockers (CCBs)
6.3.2.7 Long acting nitrates 29
6.3.2.8 Trimetazidine 30
6.3.3 Other medical therapy 31
6.3.3.1 NSAIDs and COX 2 inhibitors 31
6.4 Myocardial Revascularisation 31
6.4.1 Percutaneous Coronary Intervention (PCI) 32
6.4.2 Coronary Artery Bypass Grafting (CABG) 32
6.4.3 Percutaneous Coronary Intervention (PCI) versus Coronary
32
Artery Bypass Grafting (CABG)
6.4.4 Revascularisation versus medical therapy 33
6.5 Special Sub-groups 34
6.5.1 Women 34
6.5.2 Diabetes Mellitus (DM) 35
6.5.3 Elderly 36
6.5.4 Chronic refractory angina 37
xii
REFERENCES 38
APPENDIX 1 65
APPENDIX 2 66
APPENDIX 3 67
ABBREVIATIONS 68
ACRONYMS 70
ACKNOWLEDGMENT 71
STATEMENT OF DISCLOSURE 71
SOURCES OF FUNDING 71
xiii
1 INTRODUCTION
Coronary Artery Disease (CAD) comprises a broad spectrum of manifestation ranging
from asymptomatic atherosclerosis to symptomatic stable angina, acute coronary
syndrome (ACS) and congestive heart failure (CHF).
Local data for the prevalence of patients with SAP is not available. However in 2008,
cardiovascular disease (CVD) was the commonest cause of death in MOH hospitals at
25.19% of total deaths.1
Data from USA shows that SAP is the initial presenting manifestation in approximately
half of patients with CAD.2,3
Reported annual incidence of angina is 213 per 100 000 population greater than 30
years old.2 Annual incidence of uncomplicated angina pectoris in western population
aged > 40 years is approximately 0.5% with geographic variations.3,4-10
Prevalence of angina varies according to sex and age ranging from 0.1-1% in women
aged 45-54 years, 10-15% in women aged 65-74 years to 2-5% in men aged 45-54 years
and 10-20% in men aged 65-74 years.11-18
The management of SAP has not been extensively studied with large Randomised
Clinical Trials as other parts of the disease spectrum hampering efforts to define an
optimum strategy for management of SAP.
2. DEFINITION AND PATHOPHYSIOLOGY

2.1 DEFINITION
ANGINA
Clinical syndrome characterised by:
• Discomfort in chest, jaw, shoulder, back or arms
• Typically aggravated by exertion or emotional stress
• Relieved by rest or nitroglycerin (GTN)
Unstable Angina (UA) may present in the following ways:19

Table 1. Presentation of UA
Type Description
Rest angina Pain of characteristic nature and location, but
occurring at rest and for prolonged periods, up to
20 min
Crescendo angina Previously stable angina, which progressively
increases in severity, intensity, and at lower
threshold over a short period of 4 weeks or less
New-onset angina Recent onset of severe angina, such that the
patient experiences marked limitation of ordinary
activity within 2 months of initial presentation
1
This CPG is a guide for the management of patients with angina who do not fulfill
the criteria of UA.
2.2 PATHOPHYSIOLOGY
The syndrome is attributed to myocardial ischaemia, the most common cause being
atherosclerotic CAD.
Other causes of myocardial ischaemia include:

• Hypertrophic cardiomyopathy
• Aortic stenosis
• Coronary vasospasm
• Coronary vasculitis from connective tissue disease
• Aortic aneurysms
• Coronary artery anomalies
• Anemia
Myocardial ischaemia is caused by an imbalance between myocardial oxygen supply

and demand.
Coronary arterial flow which is dependant on luminal cross-sectional area and

arteriolar tone, is a major determinant of myocardial oxygen supply.
Mismatch in myocardial oxygen supply and demand results in metabolic abnormalities,

regional or global myocardial dysfunction, ECG changes and angina.
In SAP, angina threshold may vary from day to day or even within the same day.
Table 2. Canadian Cardiovascular Society Classification (CCS) of Angina

Limitation of
Class Severity of exertional stress inducing angina
ordinary activity
Strenuous, rapid or prolonged exertion at
I None
work or recreation
Walking or climbing stairs rapidly, walking
uphill, walking or stair climbing after
II meals, or in cold, or in wind, or under Slight
emotional stress, or only during the few
hours after awakening
Walking one or two blocks on the level and
III climbing one flight of stairs in normal Marked
conditions and at a normal pace.
Inability to carry out any physical activity
Discomfort in all
IV without discomfort or symptoms may be
activity performed
present at rest
Patients with SAP may become unstable. UA is characterised by angina which may be
more prolonged, more frequent, more severe, occurring at a lower threshold or at
rest20 and patients may progress to non-ST-elevation or ST- elevation MI. (For
management of UA or MI, please refer to the Malaysia Clinical Practice Guidelines on
2
UA/NSTEMI21 and Clinical Practice Guidelines on Management of Acute ST Segment
Elevation Myocardial Infarction (STEMI) 200722)
3 PROGNOSIS
European data estimates CAD mortality rates for men of 17.6 per 1000 patient-years
between 1970s and 1990s.18,23 In the Framingham Heart Study, 2-year incidence rates
for non-fatal MI and CAD death were 14.3% and 5.5% in men and 6.2% and 3.8% in
women, respectively.3,24
Annual mortality rates from clinical trial on anti-anginal therapies and or

revascularisation ranges between 0.9-1.4%.25-29 However, the prognosis for each
patient may vary considerably and the individual prognostic assessment is an integral
part of management of patients with SAP.
4 DIAGNOSIS AND ASSESSMENT

• Diagnosis and assessment of angina involves clinical assessment, laboratory
tests, and specific cardiac investigations.
• In practice, diagnostic and prognostic assessments are conducted in tandem
rather than separately, and many of the investigations used for the diagnosis
also offer prognostic information.
• An algorithm for the initial evaluation of patients presenting with clinical
symptoms suggestive of angina is depicted in Figure 1 (Page X)
4.1 Symptoms and signs

• A careful history alone may be enough for the diagnosis of angina pectoris, and
confirmation is made by physical examination and objective tests.
• The characteristics of discomfort related to myocardial ischaemia (angina
pectoris) may be divided into four categories, summarised in Table 3 below:
Table 3. The characteristics of discomfort related to myocardial

ischaemia (angina pectoris)
Characteristics Examples
Location Classically retrosternal, but may be felt anywhere
from the epigastrium to the jaw or teeth, between
the shoulder blades or in either arm to the wrist
and fingers.
Character Pressure, tightness, or heaviness, sometimes
strangling, constricting, or burning. The severity of
the discomfort varies greatly and is not related to
the severity of the underlying coronary disease.
Shortness of breath may accompany angina.
Duration Not more than 10 minutes in the majority of cases
Exacerbating Symptoms classically get worse with increased
and relieving levels of exertion, and rapidly disappear at rest
factors within a few minutes. Exacerbations of symptoms
after a heavy meal, during emotional stress or first
thing in the morning are features of angina.
Sublingual nitrates may rapidly relieve angina.
3
Definitions of typical and atypical angina have been previously published30 and are
summarised in Table 4.
Table 4. Clinical classification of chest pain

Type Characteristics
Typical angina (definite) Meets three of the following
characteristics
• Retrosternal chest discomfort of
characteristic quality and duration
• Provoked by exertion or emotional
stress
• Relieved by rest and/or GTN
Atypical angina Meets two of the above characteristics
(probable)
Non-cardiac chest pain Meets one or none of the above
characteristics
Non-anginal pain lacks the characteristic qualities described above and non-
cardiac causes of pain should be evaluated in such cases.
Table 5. Causes of non-anginal chest pain

Underlying cause System Specific condition
involvement
Gastrointestinal Gastro-oesophageal
system reflux
Peptic ulcer disease
Oesophageal spasm
Gallstones
Respiratory Pleurisy
Non-cardiovascular system Pneumothorax
Pulmonary embolism
Pneumonia
Neurology Neuralgia
Psychiatry Psychosomatic
Musculoskeletal Costochondritis
Myalgia
Cardiac Mitral valve prolapse
Cardiovascular
Pericarditis
(not myocardial
Non-cardiac Aortic dissection
ischaemia)
Unstable Angina (UA)

• It is important when taking the history to identify those patients with UA
• UA may present in one of three ways as defined in Table 1.
The investigation and management of suspected UA are dealt within the guidelines for
the management of ACS. (For management of ACS, please refer to the Malaysia
4
Clinical Practice Guidelines on Management of Acute ST Segment Elevation Myocardial
Infarction (STEMI) 200722)
Physical examination is directed at:

• looking for complications of CAD such as murmurs indicating mitral valvular
regurgitation, septal defects, signs of cardiomegaly and CHF
• other sites of atherosclerosis – carotid bruits, peripheral vascular disease,
aortic aneurysms
• risk factors for atherosclerosis such as hypertension, metabolic syndrome, etc
• other causes of angina such as hypertrophic obstructive cardiomyopathy
(HOCM), aortic stenosis
Investigations in stable angina may be divided broadly into 5 groups:

4.2 Laboratory tests
4.3 Chest X-Ray (CXR)
4.4 Non-invasive cardiac investigations
4.4.1 Resting electrocardiography (ECG)
4.4.2 Exercise stress testing
4.4.3 Stress testing in combination with imaging
4.4.3.1 Echocardiography (Echo)
4.4.3.2 Myocardial perfusion scintigraphy
4.4.4 Pharmacological stress testing in combination with imaging
4.4.4.1 Echocardiography (Echo)
4.4.4.2 Myocardial perfusion scintigraphy
4.4.5 Stress cardiac magnetic resonance (CMR) imaging
4.4.6 Echocardiography (Echo) at rest
4.4.7 Ambulatory electrocardiography (ECG) monitoring
4.5 Non-invasive techniques to assess coronary calcification and coronary
anatomy
4.6 Invasive techniques to assess coronary anatomy
4.2 Laboratory tests

The objectives of laboratory investigations are to:
• establish cardiovascular (CV) risk factors (eg. fasting glucose level31-34
fasting lipid profile,35-37 homocysteine,38 Lp(a), ApoA,39 ApoB39
• provide information relating to possible causes of ischaemia (eg.
haemoglobin level)40
• determine prognosis (eg. hs-CRP,38,41,42 serum creatinine43)
Recommendation of laboratory investigations

Full blood count, serum creatinine I, C
Fasting glucose I, B
Fasting lipid profile I, B
hs-CRP, homocysteine, Lp(a), ApoA, ApoB IIb, B
5
4.3 Chest X-Ray (CXR)
• In SAP, the CXR does not provide specific information for diagnosis or for risk
stratification
• The test should be requested only in patients with suspected CHF,44 valvular
disease, or pulmonary disease19
• The presence of cardiomegaly, pulmonary congestion, atrial enlargement,
and cardiac calcifications have been related to prognosis45-48
Recommendations for CXR for initial diagnostic assessment of angina

CXR in patients with suspected CHF I, C
CXR in patients with clinical evidence of significant I, B
pulmonary disease
4.4 Non-invasive cardiac investigations

This section describes investigations used in the assessment of angina and
concentrate on recommendations for their use in diagnosis and evaluation of
efficacy of treatment, whereas recommendations for risk stratification will be
dealt with in the following section.
4.4.1 Resting electrocardiography (ECG)

• All patients with suspected angina pectoris based on symptoms should have
a resting 12-lead ECG recorded
• A resting ECG may show evidences of CAD such as previous MI or an
abnormal repolarisation pattern
• A normal resting ECG does NOT exclude the diagnosis of ischaemia
• The ECG may assist in clarifying the differential diagnosis if taken in the
presence of pain such as in vasospasm, allowing detection of dynamic ST-
segment changes in the presence of ischaemia,49,50 or by identifying features
of pericardial disease.
• The ECG may also show other abnormalities such as left ventricular
hypertrophy (LVH), bundle branch block, pre-excitation, arrhythmias, or
conduction defects.
• Such information may be helpful in defining the mechanisms responsible for
chest pain, in selecting appropriate further investigation or in tailoring
individual patient treatment.
Recommendations for resting ECG for initial diagnostic assessment

of angina
Resting ECG while pain free I, C
Resting ECG during episode of pain (if possible) I, B
Recommendations for resting ECG for routine re-assessment in

patients with SAP
Routine periodic ECG in the absence of clinical change IIb, C
6
4.4.2 Exercise stress testing
• An exercise test should be carried out only after careful clinical evaluation
of symptoms and a physical examination including resting ECG
• Exercise ECG is more sensitive and specific than rest ECG for detecting
myocardial ischaemia51-56
• Exercise ECG should not be carried out routinely in patients with known
severe aortic stenosis or hypertrophic cardiomyopathy
• Interpretation of the exercise ECG test should be based on the pre-test
probability of disease19,57
• Exercise ECG testing is not of diagnostic value in the presence of
ο Left bundle branch block (LBBB)
ο Paced rhythm
ο Wolff-Parkinson-White (WPW) syndrome
• The reasons for stopping the test are listed in Table 6
• In some patients, the exercise ECG may be non-conclusive if:
ο at least 85% of maximum heart rate (HR) is not achieved in the absence
of symptoms or ischaemia
ο exercise is limited by orthopaedic or other non-cardiac problems
ο ECG changes are equivocal
• Inconclusive exercise test should then be followed by an alternative non-
invasive diagnostic test, unless the patient has a very low pre-test
probability (<10%) of disease
• For diagnostic purposes, the test should be conducted in patients without
taking anti-ischaemic drugs provided it is safe to do so
• Exercise stress testing can also be useful to evaluate the efficacy of
treatment after control of angina with medical treatment or
revascularisation or to assist prescription of exercise after control of
symptoms
• The effect of routine periodical exercise testing on patient outcomes has
not been formally evaluated
• False positive results are more frequent in patients with abnormal resting
ECG, in the presence of LVH, electrolyte imbalance, intraventricular
conduction abnormalities, and use of digitalis
• Exercise ECG testing is also less sensitive and specific in women58
7
Table 6. Reasons for terminating exercise stress test19
Reasons Examples
Symptom limitation Pain, fatigue, dyspnoea, and claudication
Combination (symptoms and Pain with significant ST-changes
ECG)
Safety reasons - Marked ST-depression (>2 mm as relative
indication for termination and 4 mm as
an absolute indication to stop the test)
- ST-elevation 1 mm
- Significant arrhythmia
- Sustained fall in systolic blood pressure
(SBP) >10 mmHg
- Marked HPT (>250 mmHg systolic or
>115 mmHg diastolic)
Achievement of maximum Decision to terminate the test is at the
predicted HR discretion of the physician
Recommendations for exercise ECG for initial diagnostic assessment

of angina
Patients with angina and intermediate-to-high pre-test I, B
a
probability of CAD unless unable to exercise or displays
ECG changes which make ECG non-evaluable
Patients with 1 mm ST-depression on resting ECG or taking IIb, B
digoxin
Patients with low pre-test probability (<10%) of CADa IIb, B
a = based on age, gender and symptoms, see appendix 1.
Recommendations for exercise ECG for routine re-assessment in

patients with SAP
Routine periodic exercise ECG in the absence of clinical IIb, C
change
4.4.3 Stress testing in combination with imaging

• The most well-established stress imaging techniques are echo and perfusion
scintigraphy and both may be used in combination with either exercise
stress or pharmacological stress
• Novel stress imaging techniques also include stress CMR, which, for logistical
reasons, is most frequently performed using pharmacological stress rather
than exercise stress
• Stress imaging techniques have several advantages over the conventional
exercise ECG testing including superior diagnostic performance (Table 7) for
the following reasons:
o
detection of obstructive CAD
o
the ability to quantify and localise areas of ischaemia
o
the ability to provide diagnostic information in the presence of resting
ECG abnormalities
8
• Stress imaging techniques are often preferred in patients with previous PCI
or CABG52 because of superiority in localising ischaemia
• In patients with angiographically confirmed intermediate coronary lesions
(50%-70% stenosis on angiography), evidence of anatomically appropriate
ischaemia is predictive of future events, whereas a negative stress imaging
test can be used to define patients with a low cardiac risk, who can be re-
assured
Table 7. Summary of test characteristics for investigations used in the

diagnosis of SAP19
Diagnosis of CAD
Sensitivity (%) Specificity (%)
Exercise ECG 68 77
Exercise echo 80-85 84-86
Exercise myocardial perfusion 85-90 70-75
Dobutamine stress echo 40-100 62-100
Vasodilator stress echo 56-92 87-100
Vasodilator stress myocardial perfusion 83-94 64-90
4.4.3.1 Exercise testing with echocardiography

• Exercise stress echo is an alternative to ‘classical’ exercise testing with ECG
and provides additional information to establish the presence or location
and extent of myocardial ischaemia during stress
• A resting echocardiogram is acquired before a symptom-limited exercise test
is performed with further image acquisition at peak exercise
• Overall sensitivity and specificity of exercise echocardiography is 80-85%
and 84-86% respectively59-62
• Tissue Doppler and strain rate imaging are expected to improve the
accuracy and reproducibility of stress echo in the broader clinical setting63-66
4.4.3.2 Exercise testing with myocardial perfusion scintigraphy

• Thallium-201 and technetium-99m 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
• It produces images of regional tracer uptake that reflects relative regional
myocardial blood flow. Myocardial hypoperfusion is characterised by
reduced tracer uptake during stress in comparison with uptake at rest
• It is more sensitive and specific than exercise ECG (Table 7)61,62,67,68
4.4.4 Pharmacological stress testing with imaging techniques

• Pharmacological stress may also be employed when the use of exercise
imaging is not possible
• Pharmacological stress testing with either perfusion scintigraphy or
echocardiography is indicated in patients who are unable to exercise
adequately or may be used as an alternative to exercise stress
• Two approaches may be used to achieve this:
o infusion of short-acting sympathomimetic drugs (eg. dobutamine)69
o infusion of coronary vasodilators (eg. adenosine and dipyridamole)
9
• The diagnostic performance of pharmacological stress perfusion and
pharmacological stress echo is also similar to that of exercise imaging
techniques (Table 7)60,61
• Stress imaging has an important role to play in evaluating patients with a
low pre-test probability of disease, particularly women, 70-73when exercise
testing is inconclusive, in selecting lesions for revascularisation and in
assessing ischaemia after revascularisation74-77
Recommendations for the use of exercise stress with imaging

techniques (either echo or perfusion) in the initial diagnostic
assessment of angina
Patients with resting ECG abnormalities eg LBBB, >1 mm ST- I, B
depression, paced rhythm, or WPW which prevent accurate
interpretation of ECG changes during stress
Patients with a non-conclusive exercise ECG but reasonable I, B
exercise tolerance, who do not have a high probability of
significant coronary disease and in whom the diagnosis is
still in doubt
Patients with prior revascularisation (PCI or CABG) in whom IIa, B
localisation of ischaemia is important
As an alternative to exercise ECG in patients where IIa, B
facilities, costs, and personnel resources allow
As an alternative to exercise ECG in patients with a low pre- IIa, B
test probability of disease
To assess functional severity of intermediate lesions on IIa, C
coronary arteriography
To localise ischaemia when planning revascularisation IIa, C
options in patients who have already had arteriography
Recommendations for the use of pharmacological stress with imaging

techniques (either echo or perfusion) in the initial diagnostic
Class I, IIa, and IIb indications as mentioned earlier, if the patient is unable
to exercise adequately
4.4.5 Stress Cardiac Magnetic Resonance (CMR)

• Stress CMR can be used to detect wall motion abnormalities induced by
ischaemia or perfusion abnormalities
• Stress CMR, using either perfusion imaging or stress-induced wall motion
abnormalities imaging, demonstrates good sensitivity 83-91% and specificity
81-86% for the diagnosis of CAD.78
• High quality CMR perfusion has been shown to be at least as good as single
photon emission computed tomography scan (SPECT) for the diagnosis of
CAD. It also has a close correlation with invasive flow and pressure
measurements.79
• Dobutamine stress CMR has been shown to be superior to adenosine stress
CMR to detect ischaemia in patients with suspected or known CAD but no
history of prior MI80
10
4.4.6 Echocardiography (Echo) at rest
• Two-dimensional and doppler echo is useful in patients with clinically
detected murmurs,81-84 history and ECG changes compatible with
hypertrophic cardiomyopathy85,86 or previous MI87,88 and symptoms or signs
of CHF89,90
• Recent developments in tissue Doppler imaging and strain rate
measurement have greatly improved the ability to study diastolic
function66,91
Recommendations for echo for initial diagnostic assessment of angina

Patients with abnormal auscultation suggesting valvular I, B
heart disease or hypertrophic cardiomyopathy
Patients with suspected CHF I, B
Patients with prior MI I, B
Patients with LBBB, Q waves or other significant I, C
pathological changes on ECG, including left anterior
hemiblock
4.4.7 Ambulatory electrocardiographic (ECG) monitoring

• Ambulatory ECG (Holter) monitoring may reveal evidence of myocardial
ischaemia during normal ‘daily’ activities92
• However, it rarely adds important diagnostic or prognostic information in
chronic stable angina pectoris over and above that provided by an exercise
test93,94
• It may have a role in patients in whom vasospastic angina is suspected
• In patients with SAP and suspected major arrhythmias, Holter monitoring is
an important method of diagnosing arrhythmias
Recommendations for ambulatory ECG for initial diagnostic

Angina with suspected arrhythmia I, B
Suspected vasospastic angina IIa, C
4.5 Non-invasive techniques to assess coronary calcification and

coronary anatomy
There are 3 non-invasive modalities to define the coronary anatomy:

1. Electron beam computed tomography (EBCT) with/without angiogram
2. Multislice computed tomography (MSCT) angiogram
3. Cardiac magnetic resonance (CMR)
4.5.1 Electron beam computed tomography (EBCT)

The EBCT is effective in quantifying the extent of coronary calcification.95-97 The
coronary calcium score identifies a population at higher risk of significant coronary
artery disease, and has been found to correlate well with overall burden of
plaque.98 However, due to low spatial resolution and high image noise, EBCT
angiogram is not an appropriate diagnostic tool for patients with SAP.99
11
4.5.2 Multislice computed tomography (MSCT)
Cardiac CT is performed as a 2-part examination. Firstly, the coronary artery
calcium score and secondly the coronary artery CT angiogram.100 The use of MSCT
angiogram allows good diagnosis, accurate detection and quantification of stenosis
of major segments of right and left coronary arteries. The 64 slice detector CT
angiogram has a negative predictive value of 93-99% and sensitivities and
specificities of 90-94% and 95-97% respectively.101,102
Recommendations for the use of CT angiography in SAP

Diagnosis of CAD when other modalities (eg., stress testing or stress
IIa, C
imaging) provide equivocal results, especially in patients with a low
to intermediate probability of disease
Patients who cannot undergo non-invasive testing due to disability,
IIb, C
illness, or morbid obesity
Patients with recurrent chest pain in whom a definite diagnosis is
IIb, C
judged necessary
4.5.3 Cardiac Magnetic Resonance (CMR)

CMR is an emerging modality for cardiac imaging. It is an excellent modality for
evaluation of myocardial structure, function, reversible ischaemia and viability,
however the current MRI technology has limited diagnostic accuracy for
assessment of coronary stenosis.103
4.6 Invasive techniques to assess coronary anatomy

4.6.1 Coronary angiography
Coronary angiography is defined as the radiographic visualisation of the coronary
vessels after injection of radiopaque contrast media. Coronary angiography allows
anatomical definition of the coronary arteries, degree of luminal obstruction and
determination of prognosis. The risk of complications with routine angiogram is
between 1 and 2% with the current methods.104 The composite rate of death, MI,
or stroke is of the order of 0.1-0.2%.104
12
Recommendations for coronary angiography for establishing a diagnosis of SAP
Severe SAP (Class 3 or greater of CCS Classification), with a high
pre-test probability of disease, especially if symptoms are not I, B
responding to medical treatment
Survivors of cardiac arrest I, B
Patients with serious ventricular arrhythmias I, C
Patients previously treated by myocardial revascularisation (PCI,
CABG) who develop early recurrence of moderate or severe angina I, C
pectoris
Patients with an inconclusive diagnosis on non-invasive testing, or
conflicting result from different non-invasive modalities at IIa, C
intermediate to high risk of coronary disease
Patients with a high risk of restenosis after PCI if PCI has been done
IIa, C
in a prognostically important site
Patients who cannot undergo non-invasive testing due to disability,
IIa, C
illness, or morbid obesity
Patients with a high pre-test probability of left main or 3-vessel
IIa, C
CAD
Patients with significant LV dysfunction (left ventricular ejection
fraction (LVEF) <45%), CCS class I or II angina, and demonstrable IIa, C
ischaemia but less than high-risk criteria on non-invasive testing
Patients with recurrent chest pain in whom a definite diagnosis is
IIb, C
judged necessary
Patients with significant co-morbidity in whom the risk of coronary
III, C
arteriography outweighs the benefit of the procedure
Adjunctive invasive techniques with coronary angiography for assessment of CAD

include intravascular ultrasound (IVUS), fractional flow reserve (FFR) and coronary
angioscopy.
5 RISK STRATIFICATION
The process of risk stratification serves 2 purposes:
• To provide information regarding prognosis
• To assist in choosing appropriate treatment, eg. revascularisation in high risk
groups
While clear risk stratification exists for primary prevention, absolute levels of what
constitutes high risk and low risk are not clearly defined for those with established
CVD. Risk stratification primarily refers to the risk of cardiovascular death. However,
there is no systematic predictive method to determine what constitutes high risk or
low risk.105,106 The Euro heart angina score probably provides the simplest and most
objective way to discriminate extremely low risk group and those at high risk.
Comorbidity, diabetes, severity of angina, duration of symptoms, left ventricular
function and ST segment changes on resting ECG independently predict outcome, i.e.
non-fatal MI and death.107
13
For the purposes of these guidelines, an individual with SAP is deemed:
• high risk - if he has annual CV mortality of >2%108
• intermediate risk – if he has annual CV mortality of 1-2%
• low risk – if he has annual CV mortality of <1%109
Information required to stratify a patient's risk:

A. Clinical evaluation
B. Non-invasive assessment of ischaemia
C. Quantification of ventricular function
D. Extent of CAD (angiography)
5.1 Clinical Evaluation46,94,105,110-112

5.1.1 Clinical history
Important predictors of adverse outcome in patients with established CAD105,106:
• DM37,38,113-116
• HPT37,38,114-116
• Metabolic syndrome
• Current smoking37,38,114-116
• Increasing age45,110
•
Prior MI45,110
• Symptoms and signs of CHF45,46,110
• Pattern of occurrence of angina (recent onset or progressive)112,117
• Severity of angina, particularly if unresponsive to therapy112,117
• Dyslipidaemia
5.1.2 Physical examination

The presence of the following assists in determining risk:
• peripheral vascular disease (PVD) - either lower limb or carotid118,119
• signs related to CHF
5.2 Resting ECG

Resting ECG abnormalities can predict patients at greater risk of future CV events
than those with a normal ECG. 23,120-123 The abnormalities are:
• Evidence of prior MI
• LBBB
• Left anterior hemiblock,
• LVH
• Second or third degree AV block
• Atrial fibrillation (AF)
Recommendations for risk stratification by clinical evaluation, including

ECG and laboratory tests, in SAP
Detailed clinical history and physical examination – including BMI
I, B
and/or waist circumference and CV risk profile
Resting ECG I, B
14
5.3 Stress Testing46,94,105,110-112
Risk stratification using stress testing
• Stress testing can be in the form of exercise or pharmacological stress, with
or without imaging.
• Prognostic information that can be obtained from stress testing:
o detection of ischaemia
o ischaemic threshold
o extent and severity of ischaemia (for imaging techniques)
o functional capacity (for exercise testing)
• The choice of initial stress test should be based on the patient's resting ECG,
physical ability to perform exercise, local expertise, and available
technologies.
• Commonly used stress testing modalities are:
1. Exercise stress test
2. Stress echo
3. Stress perfusion scintigraphy
5.3.1 Exercise stress test

• Prognostic exercise testing markers include exercise capacity and exercise-
induced ischaemia (clinical and ECG).
• Maximum exercise capacity is a consistent prognostic marker. It may be
measured by
o maximum exercise duration
o maximum MET level achieved
o maximum HR
o double (rate–pressure) product
• In patients with known CAD and normal or mildly impaired LV function, the 5-
year survival is higher in patients with a better exercise tolerance.45,56,124-126
• An early positive exercise test (ST depression > 1mm within stage 1 or 2 of
standard Bruce protocol) identifies a high risk population126
• The Duke treadmill score (DTS) is a well-validated score which combines
exercise time, ST deviation, and angina during exercise to calculate the
patient's risk (Figure 2).124,127
Duke treadmill score Score

a. Exercise time (in minutes) n
b. ST-depression (mm x 5) -n
c. Angina (non-limiting) OR -4
d. Angina (limiting) -8
Total score = a + b + (c OR d)
Risk Total score 1-year mortality

Low ≥5 0.25%
Intermediate 4 to -10 1.25%
High ≤ -11 5.25%
Figure 2 DTS score.127
15
Recommendations for risk stratification according to exercise stress ECG in
SAP in patients who can exercise
All patients without significant resting ECG abnormalities
I, B
undergoing initial evaluation
Patients with stable coronary disease after a significant change
I, C
in symptom level
Patients post-revascularisation with a significant deterioration in
IIa, B
symptomatic status
5.3.2 Stress echocardiography

• May be used to risk stratify patients at risk of CV events62,128
• Has an excellent negative predictive value in patients with a negative test
having an event rate (death or MI) of <0.5% per year129,130
• Risk of future events is influenced by the number of
o resting regional wall motion abnormalities
o inducible wall motion abnormalities on stress echo59
• Identification of a high risk cohort allows for appropriate further investigation
and/or intervention
Recommendations for risk stratification according to exercise stress

imaging (perfusion or echo) in SAP in patients who can exercise
Patients with resting ECG abnormalities eg. LBBB, >1 mm I, C
ST-depression, paced rhythm, or WPW which prevent
accurate interpretation of ECG changes during stress
Patients with a non-conclusive exercise ECG, but I, B
intermediate or high probability of disease
Patients with a deterioration in symptoms post- IIa, B
revascularisation
As an alternative to exercise ECG in patients, in which IIa, B
facilities, cost, and personnel resources allow
5.3.3 Pharmacological stress echocardiography

• Dobutamine and vasodilators (e.g. dipyridamole) at appropriately high doses
are equally potent ischaemic stressors and have similar accuracies and
specificities to exercise132-134
• The presence (or absence) of inducible wall motion abnormalities separates
patients with different prognosis129,135-149
• Normal stress echocardiogram yields a cardiac event risk of 0.4% to 0.9%150
Recommendations for risk stratification according to pharmacological

stress imaging (perfusion or echo) in SAP
Patients who cannot exercise I, B
Other class I and II indications as for exercise stress imaging
(perfusion or echocardiography) in SAP in patients who can
exercise, but where local facilities do not include exercise
imaging
16
5.3.4 Stress perfusion scintigraphy
• Normal stress myocardial perfusion images carries a benign prognosis, with an
event rate of <1% per year, which is nearly as low as that of the general
population.151-153
• The only exceptions would appear to be patients with normal perfusion
images with either a high-risk treadmill ECG score or severe resting LV
dysfunction154
• In contrast, abnormal findings have been associated with severe CAD and
subsequent cardiac events
• Large stress-induced perfusion defects, defects in multiple coronary artery
territories, transient post-stress ischaemic LV dilatation, and in patients
studied with thallium-201, increased lung uptake155 on post-exercise or
pharmacologic stress images are all adverse prognostic indicators.62,68,153,154
• Exercise stress imaging offers greater prognostic information than
pharmacological stress imaging because of the information regarding
symptoms, exercise tolerance and haemodynamic response to exercise, which
is additive to that obtained from perfusion or echo data alone.
5.3.5 Stress Cardiac Magnetic Resonance (CMR)

• In patients with known or suspected CAD, myocardial ischaemia detected by
adenosine and dobutamine stress CMR can be used to identify patients at high
risk for subsequent cardiac death or non-fatal MI. For those with normal
stress CMR, the 3-year event-free survival was 99.2%.156
• Adenosine stress CMR imaging is safe to perform early after acute STEMI and
can identify patients with significant coronary stenosis more accurately than
exercise stress test.157
• Adenosine stress CMR may help to identify patients at risk who would benefit
from intensified medical treatment and close follow-up.158
5.4 Ventricular function46,94,105,110-112

Risk stratification using ventricular function
• Strongest predictor of long-term survival is LV function
• Prevalence of asymptomatic ventricular dysfunction has been reported to be
as high as twice that of clinical CHF, with the presence of IHD a major risk
factor for its occurrence.159-161
• In patients with SAP, as LVEF declines, mortality increases.
• Resting LVEF of <35% is associated with an annual mortality rate >3% per
year45,46,111,162
• An estimation of ventricular function is desirable in risk stratifying patients
with SAP, and an assessment for ventricular hypertrophy (by echo or MRI) and
of ventricular function is particularly pertinent in patients with HPT163 or DM.
LVEF 12-year survival rate19

(P<0.0001)
<35% 21%
35–49% 54%
>50% 73%
17
Recommendations for risk stratification by echo evaluation of ventricular
function in SAP
Resting echo in patients with prior MI, symptoms or signs of
I, B
CHF, or resting ECG abnormalities
Resting echo in patients with HPT I, B
Resting echo in patients with DM I, C
Resting echo in patients with a normal resting ECG without
prior MI who are not otherwise to be considered for coronary IIa, C
arteriography
5.5 Coronary arteriography46,94,105,110-112

Risk stratification using coronary arteriography
• Despite the recognised limitations of coronary arteriography to identify
vulnerable plaques which are likely to lead to acute coronary events, the
following have been convincingly demonstrated to be important prognostic
indicators in patients with angina.46,111,164,165
o extent of CAD (number of vessels involved)
o severity of luminal obstruction
o location of coronary disease (left main stem (LMS) and proximal left
anterior descending artery (LAD)
• In the CASS registry of medically treated patients, the 12-year survival rate of
patients with normal coronary arteries was 91% compared with 74% for those
with single vessel disease, 59% for those with two-vessel disease (2VD), and
50% for those with three-vessel disease (3VD) (P<0.001).162
• The 5-year survival rate for patients with 3VD including a >95% proximal LAD
stenosis was 54% compared with a rate of 79% for patients with 3VD without
LAD stenosis.165
• The use of coronary arteriography to identify patients whose prognosis can be
improved is likely to be appropriate in high but not low risk groups.
• In the intermediate risk group, the decision should be guided by a variety of
factors including the patient's symptoms, functional status, lifestyle,
occupation, co-morbidity, and response to initial medical therapy.
• It is the duty of the physician to ensure that the patient is fully informed of
their risk and the potential benefits or lack of benefit of any particular
procedure and to guide their decision appropriately.
• Coronary arteriography should NOT be performed in patients
o with angina who refuse invasive procedures
o who prefer to avoid revascularisation
o who are not candidates for PCI or CABG
o in whom PCI/CABG will not improve quality-of-life
18
Recommendations for risk stratification by coronary arteriography in
patients with SAP
Patients determined to be at high risk for adverse outcome on the
basis of non-invasive testing even if they present with mild or I, B
moderate symptoms of angina
Severe SAP (Class 3 or greater of CCS Classification), particularly if
I, B
the symptoms are inadequately responding to medical treatment
SAP in patients who are being considered for major non-cardiac
surgery, especially vascular surgery (repair of aortic aneurysm,
I, B
femoral bypass, carotid endarterectomy) with intermediate or
high risk features on non-invasive testing
Patients with an inconclusive diagnosis on non-invasive testing, or
IIa, C
conflicting results from different non-invasive modalities
Patients with a high risk of restenosis after PCI, if PCI has been
IIa, C
performed in a prognostically important site
A summary of the recommendations for the routine use of investigations in the

evaluation of SAP, with corresponding levels of evidence related to diagnosis and
prognosis, is presented in Appendix 2.
6 TREATMENT
6.1 Aims of treatment:
Generally treatment is aimed to:
• prevent MI and death
• minimise or abolish symptoms of angina thereby improving quality of life (QoL)
6.2 General Management

Life-style modification should be emphasised to all patients with SAP in addition to
pharmacological measures and revascularisation. Symptoms can be improved in most
patients with appropriate measures.
Upon comprehensive risk stratification (see section 5):

• patients and close relatives should be well-informed of the nature and
prognosis of the disease as well as the implication of the diagnosis
• treatment goals and strategies should be discussed to improve compliance
• life-style risks should be identified and managed accordingly
6.2.1 Life-style modification

6.2.1.1 Smoking cessation
Smoking is strongly discouraged. This is the most important reversible risk factor.
Smoking cessation greatly improves symptoms and prognosis. There was a 36%
relative reduction in mortality and a 32% relative reduction in non-fatal MI for
patients with CHD who quit smoking compared with those who continue to
smoke.166
Nicotine replacement therapy is safe and helpful.167 If possible, patient should be
referred to centres with expertise in smoking cessation because a structured
smoking cessation program has a higher success rate than brief office advice.168
Table 8 below provides the list of available nicotine replacement therapy
available in Malaysia.
19
Varenicline tartrate is now available and effective in smoking cessation. It has
proven efficacy and safety in general population.169,170 The same treatment
regime is advocated for CAD patients.171
However there has been some safety concerns by Food and Drug Administration in
the United States regarding the risk of depression and suicidal thoughts.
Clinicians may want to refer to Malaysia Clinical Practice Guidelines on Treatment

of Tobacco Use and Dependence.172
Table 8. Nicotine replacement therapy available in Malaysia172

Nicotine Recommended Regime
replacement
therapy
Nicotine gum
• Nicorette® 2mg • Use 2 mg gum for patients smoking less than 20
• Nicorette® 4mg cigarettes per day
• Use 4 mg gum for patients smoking 20 or more
cigarettes per day
• Generally, the gum should be used for up to 12
weeks with no more than 24 pieces/day
• Clinicians should tailor the dosage and duration of
therapy to fit the needs of each patient
Nicotine patch • Applied on skin as soon as the patient wakes on
1. Nicorette® their quit day
• Use 15 mg x 8 weeks, then 10 mg x 2 weeks and
finally 5 mg x 2 weeks
2. Nicotinell® • Applied on skin as soon as the patient wakes on

• TTS10 (7mg) their quit day
• TTS20 (14mg) • For patient smokes > 20 cig/day, use:
• TTS30 (21mg) TTS30 for 1-4 weeks
TTS20 for 5-8 weeks
TTS10 for 9-12 weeks
• For patient smokes < 20 cig/day, use:
TTS20 for 1-4 weeks
TTS20 for 5-8 weeks
TTS10 for 9-12 weeks
Nicotine inhaler • 6-16 cartridges/day up to 6 months of treatment
(4 mg/cartridge) • Taper dosage during the final 3 months of
treatment
Varenicline • Day 1-3: 0.5 mg once daily
tartrate • Day 4-7: 0.5 mg bd
• Day 8-end of treatment: 1 mg bd
• Duration: 12 wk. If successful stopped at 12 wk,
an additional course of 12 wk treatment may be
considered
• Quit date is set 1-2 wk before taking varenicline
20
6.2.1.2 Dietary control and fibre intake
Dietary intervention is an effective adjunct measure if properly implemented.
173,174
Healthy eating and appropriate dietary intervention have favourable effects
on many CAD risk factors175 notably HPT, hypercholesterolaemia, obesity and DM.
Patients should be encouraged to adopt a healthy eating habit,176 which includes

• Eating a variety of fruits, vegetables, legumes, nuts, soy products, low-fat
dairy products, and whole grain breads, cereals and pastas
• Minimising the intake of foods high in saturated and trans-fats, such as red
meat, whole milk products, and pastries
Polyunsaturated fat is preferable to monounsaturated fat because it is associated

with lower CV mortality in patients after MI.177-179 However, there has been no
direct study on patients with stable CAD. Food high in polyunsaturated fat
include:
• oily fish
• walnuts
• sesame and pumpkin seeds
• vegetable oils such as sunflower oil
The intensity of dietary changes is guided by abnormality of patients’ lipid

profile, weight, DM and blood pressure (BP) control. An ideal body weight and
waist circumference should be aimed for if achievable with appropriate calorie
intake.
Clinicians may want to refer to the respective clinical practice guidelines for CV
risk factors management.
Table 8. Targets for BMI 180

Group BMI (kg/m²) Risk of co-morbidities
Underweight <18.5 Low (but increased risk of other
clinical problems)
Ideal 18.5 – 22.9 Average: target for BMI
Pre-obese 23.0 – 27.4 Increased
Obese I 27.5 – 34.9 Moderate
Obese II 35.0 – 39.9 Severe
Obese III > 40.0 Very severe
Targets for waist circumference (Malaysia Clinical Practice Guideline Clinical

Practice Guidelines on Management of Obesity, 2003):180
• Men < 85 cm
• Women < 80cm
Increase intake of soluble fibres is encouraged because it has been shown to have
a small but significant reduction in total cholesterol and LDL cholesterol level in
meta-analysis among healthy subjects and high risk patients for CAD.181 Soluble
fibre is found in oats, peas, beans, legumes (dhall, chickpeas, red beans and
green beans), apples, citrus fruits, carrots, and barley. High fibre intake was also
associated with reduced risk of MI and death from CAD in cohort studies among
healthy subjects.182,183 Patients should be advised to increase total fibre intake by
21
including 3 servings of vegetables and 2 servings of fruits daily. They should also
increase whole grains such as brown rice, whole wheat breads and chapatti.184
The benefit of soluble fibres should not be denied for patients with stable CAD
despite insufficient evidence on the benefit of increasing fibre intake among
patients with CAD.
6.2.1.3 Alcohol restriction
Alcohol intake at moderation may be beneficial in reducing the population risk of
CV events.185 There is insufficient evidence to recommend alcohol consumption
among patients with stable CAD. It is also generally difficult to quantify units of
alcohol intake by general public.186,187
6.2.1.4 Physical activity
Patients should be encouraged to engage in physical activities within their limits.
The minimal goal should be 30mins, 3-4 days per week. Moderate intensity
aerobic activities are recommended eg. brisk walking.
Physical activity is beneficial on weight reduction, BP control, lipid abnormalities,

glucose tolerance and insulin sensitivity. Several randomised control trials and
meta-analysis have demonstrated improvement in mortality, symptoms and
exercise tolerance with exercise programs.188-190
Regular exercise is recommended, but individual fitness and severity of symptoms

should be taking into consideration. Exercise stress test can assist in prescription
of an appropriate exercise program.
Recommendation for lifestyle modification

Smoking cessation I, C
Dietary control & fibre intakes
• Healthy dietary choices I, B
• Use of polyunsaturated fat I, C
• Fibre intake I, C
Moderate alcohol intake II, C
Physical activity 30 min 3-4 days per week I, A
6.2.2 Health supplements

6.2.2.1 Omega-3 fatty acids
Omega-3 fatty acids are generally found in fish oil. Epidemiological studies in the
populations showed that men who ate at least some fish weekly had a lower CAD
mortality than men who ate none.191 Large control trials using up to 1g of omega-
3 fatty acids daily reduced the risk of sudden death in patients with recent
MI.192,193 However, there is no clear evidence of benefit among stable CAD
patients.194
6.2.2.2 Vitamins, anti-oxidants and other health supplements
Generally the use of vitamins, anti-oxidants, garlic and co-enzyme Q10 for stable
CAD patient is not encouraged.176 There is generally lack of evidence for CV
mortality benefit from these supplements. Morbidity benefit from co-enzyme Q10
was shown only among patients with CHF.
22
Recommendation for health supplements
Use of omega-3 fatty acids II, C
Use of vitamins, anti-oxidants and other health III, A
supplements
6.2.3 Others
6.2.3.1 Psychological factors

Diagnosis of CAD often leads to excessive anxiety and depressions.195,196
Psychological factors may provoke attacks of angina and are associated with a
higher risk of coronary mortality.197-199 Anxiety and depression should be actively
screened for and treated. Cardiac rehabilitation and self-management
empowerment has been shown to improve psychological, physical symptoms and
functional status.200 The patients should be properly educated on:
• Characteristic of their disease
• Personal risk factors
• Therapeutic life-style changes to address the risk factors
• Treatment goals and prognosis
• Action plan during an angina attack
6.2.3.2 Sexual activity

Sexual activity is no more stressful to the heart than a number of other natural
daily activities eg. walking one mile (1.6km) on the level in 20 minutes (table
28). Patients who can engage in activities requiring METs score rating between
3-4 can safely resume non vigorous sexual activities because they have low
cardiac risk. Patients who do not fulfill this criterion should be referred for
further assessment by a specialist.
Sexual intercourse may trigger angina. GTN may be helpful prior to intercourse.
Phosphodiesterase-5 (PDE-5) inhibitors can be prescribed safely201,202 but should
not be used in those receiving any nitrates.
Table 9. METs score rating of some daily activities203

Daily activity METs Score
Rating
Sexual intercourse with regular partner
• lower range (“normal”) 2–3
• upper range (vigorous activity) 5-6
Lifting and carrying objects (9 – 20kg) 4-5
Walking one mile in 20 minutes on the level 3–4
Golf 4–5
Gardening (digging) 3–5
DIY, wallpapering, etc 4–5
Light housework (eg. ironing, polishing) 2–4
Heavy housework (eg. making beds, scrubbing floors) 3-6
6.2.3.3 Employment
Patient should be encouraged to continue their occupation with appropriate
adjustment as necessary to avoid angina episodes.
23
6.2.3.4 Heavy vehicle driving
Patients are prohibited to drive commercial public transport/heavy vehicles if
they are symptomatic or suffer from complications of CAD like CHF and
arrhythmias.204
Recommendation for others

Psychological factors I, B
Sexual activity I, B
Heavy vehicle driving III, C
6.2.4 Hypertension, Diabetes Mellitus and other disorders

Concomitant HPT, DM and other features of metabolic syndrome should be
addressed as these are major risk factors to CAD.205
The target BP for patients with CAD is <130/80mmHg.21,22 Beta-blockers,

ACEIs206-208 and long acting CCBs,28 are the drugs of choice. Pharmacological
intervention is necessary if target is not achieved upon diagnosis.
DM should be managed carefully with the target HbA1c < 6.5%.209 The target
level for HbA1c must be individualised based on risks of hypoglycaemia and
quality of life.209,210 Hypoglycaemia must be avoided as it may precipitate
angina attack and increase mortality.211
Hypercholesterolaemia should be controlled to target. (Table 10) Please refer

to Clinical Practice Guidelines on Dyslipidaemia 2003.212
Table 10. Targets for cholesterol levels212

LDL should not exceed 2.6 mmol/l I, A
cholestero < 1.8 mmol/l is reasonable goal213-218
l
HDL > 1.0 mmol/l (male) I, B
cholestero >1.2 mmol/l (female)
l
Triglyceri < 1.7 mmol/l I, C
de
Note:
• In patients with triglyceride of > 2.3 mmol/l, a non-HDL cholesterol of ≤ 3.4
mmol/l should be aimed for.
• It should be emphasised that LDL-cholesterol is the primary target of
therapy. HDL-C and triglyceride are the secondary targets.
Anaemia and hyperthyroidism, if present should be corrected.
24
6.3 Pharmacological treatment of SAP
The goals of:
1. Acute treatment are:
• Relieve symptoms
• Prevent provocable angina
2. Long-term treatment are:

• Improve prognosis (Reduction in CV events)
• Improve QoL by reducing severity and frequency of angina attacks
6.3.1 Acute treatment
Self-management during an acute attack of angina:

During an acute attack of angina, patient are advised to
• rest and refrain from provoking activities
• take sub-lingual/buccal GTN (tablet or spray)
• sit in order to protect against potential harm of hypotension upon use of GTN
and should be warned of possible side-effect of headache
Patient can be encouraged to use prophylactic GTN to prevent predictable

episodes. Medical advice should be sought if symptoms persist >10 minutes after
resting and/or is not relieved by three GTN
6.3.2 Long-term treatment
Pharmacological strategies are:

6.3.2.1 Anti-thrombotic agents
6.3.2.1.1 Low dose Aspirin

Aspirin inhibits COX-1 and thromboxane production and remains the main
pharmacological prevention of arterial thrombosis. Use of low dose Aspirin
(75mg)25 in stable angina and silent ischaemia are associated with lower
incidence of MI, cardiac death or stroke.219
Dosage of Aspirin should be the lowest effective to optimise the balance between
therapeutic gains and gastrointestinal side effects during chronic therapy. The
optimal anti-thrombotic dosage of aspirin appears to be 75-150 mg/day. The
SAPAT trial showed a 34% reduction of MI or cardiac death with aspirin 75 mg/day
compared with placebo in sotalol-treated patients with stable angina pectoris.25
6.3.2.1.2 Thienopyridines
Clopidogrel and Ticlopidine are thienopyridines which act as non competitive
ADP receptor antagonist with similar antithrombolic effects of aspirin.220
Clopidogrel
Clopidogrel 75mg daily is more effective compared to aspirin alone in preventing
CV complication in high risk patient especially in the peripheral vascular disease
arm.221 Combination of aspirin and Clopidogrel is not warranted in SAP.
25
Ticlopidine
Ticlopidine efficacy has been documented in stroke and PCI. However, there are
no large clinical trials to support the use of Ticlopidine in SAP. Ticlopidine has 1-
2% risk of neutropenia and thrombocytopenia and other symptomatic side-
effects
6.3.2.1.3 Other anti-thrombotic agents

Dypyridamole
Dipyridamole is not recommended for anti-thrombotic treatment in SAP due to
poor anti-thrombotic efficacy and the risk of worsening angina symptoms due to
coronary steal phenomena.222,223
Anticoagulation
Anticoagulant drugs (warfarin or thrombin inhibitor) are not indicated in SAP
without a separate indication such as AF.
6.3.2.2 Lipid Lowering Therapy

Statin therapy has been shown to reduce CV events and mortality by 20-30%.224
There has been no statin trials specifically for patients with SAP. However, the
HPS trial225 has shown a reduction in chest pain and the need for
revascularisation in patients with stable CAD. These benefits were seen
irrespective of age, gender and baseline LDL-C levels.
Many of the statin benefits could not be explained by LDL-C lowering alone and is
thought to be due to the pleiotropic effects of statins.226-228
The NCEP ATP III guidelines229 and the Malaysia Lipid CPG 2004212 recommended
target LDL-C of <2.6mmol/l in CAD or CAD-risk equivalent patients. The updated
ATP III guideline in 2004229, recommended a target of LDL-C <1.8mmol/l in high-
risk CAD patients. The 2007 update of the ACC/AHA guideline for the
management of patients with SAP230 recommends this level as reasonable for all
patients with SAP.
Recent trials231,232 have shown aggressive LDL-C reduction with high-dose statin
could halt plaque progression and induce plaque regression respectively.
If the LDL-C target is not achieved with the maximum tolerable dose of statins,
the addition of a cholesterol absorption inhibitor, ezetimide may be useful.
Many statin-treated patients continue to have recurrent CV events. This residual

risk could partly be explained by other dyslipidaemic parameters eg. low-HDL-C
and high TG, especially in patients with metabolic syndrome and T2DM.
Improvement in these non-LDL-C fractions and possible reduction of CAD
events233,234 could be achieved with the addition of a fibrate or nicotinic acid.
Combination therapy with fibrates may increase adverse effect.235,236 There is
insufficient data to recommend a target HDL-C or triglyceride level in patients
with SAP.
26
6.3.2.3 ACE-Inhibitors (ACEIs)
There are benefits of ACEIs in secondary prevention especially in post-MI patients
with depressed LV function (LVEF <40%).237-240
Recent trials have investigated the use of ACEI in CAD patients without LVD. The
HOPE206 trial (using Ramipril 10mg daily against placebo) and EUROPA207 trial
(using Perindopril 8mg daily against placebo) showed 20% reduction in composite
primary endpoints (CV death, MI ± stroke/cardiac arrest)
The PEACE109 trial utilising Trandolapril 4mg against placebo did not show benefit
in low risk patients (normal LVEF in whom CV risk factors are well controlled and
revascularisation has been performed).
However 2 large meta-analyses208,241 have shown favourable effect of ACEIs on

the outcome in CAD patients with preserved LV systolic function.
Therefore, ACEI is recommended for all patients with SAP [Class IIa
recommendation, Level A evidence] especially when there is concomitant LV
dysfunction or DM [Class I recommendation, Level A evidence]
6.3.2.4 Angiotensin Receptor Blockers (ARBs)

The effects of ARB on prognosis in IHD is less well studied and more controversial.
There has been no specific ARB-intervention trial for patients with SAP.
The significant incidence of ACEI-induced cough (up to 20% especially in Asian242

and Black populations) has encouraged the use of ARBs in patients with CVD.
In the landmark ONTARGET243 trial involving 25 260 patients aged 55 years and
above with CAD or DM plus additional risk factors with no evidence of CHF,
telmisartan was "non-inferior" to ramipril in achieving the composite endpoints of
CV death, MI, stroke, or hospitalisation for CHF. The combination of the two drugs
was associated with more adverse events without an increase in benefit.
In the TRANSCEND244 trial involving 5 926 patients with CV disease or high-risk DM

without CHF who were intolerant to ACEI, telmisartan was no better than placebo
in improving the primary composite end point of CV death, MI, stroke, or
admission to the hospital for CHF events. There was however benefits in the pre-
specified secondary outcome of CV death, MI, and stroke.
Based on current evidence, ARBs may be considered as secondary prevention

therapy in CAD patients with HPT, CHF, post MI with left ventricular dysfunction
(LVD) and diabetics when ACE-inhibition is indicated but not tolerated [Class IIa
recommendation; Level A evidence].
27
6.3.2.5 Heart rate (HR) reducing Agents
Beta-blockers and HR-reducing non-dihydropyridine calcium channel blockers (CCB)

have been the mainstay of pharmacological treatment to achieve HR reduction. We
also know that almost two-thirds of patients continue to experience an average of
two angina episodes per week despite simultaneous use of multiple anti-anginal
drugs.245
6.3.2.5.1 Beta Blockers

Beta-blockers are the first line treatment in patients with SAP. Beta-blockers
act by competitively inhibiting catecholamines from binding to β1, β2 and β3
receptors. The risk of CV death or MI was reduced by 30% with the used of beta-
blockers in post-MI trials.246 It has been extrapolated that beta-blockers may be
cardioprotective in patients with stable CAD.
A meta-regression analysis247 of effects of different beta-blockers on mortality

found non significant benefits of acute treatment. However, a 24% relative risk
reduction of mortality was noted with long-term secondary prevention.
β1 blockade by metoprolol or bisoprolol reduces cardiac events in CHF patients

while carvedilol, a non-selective beta-blocker also reduces risks of death and CV
hospitalisations in CHF.248-250 There is a lack of evidence showing benefits in this
group of patients using atenolol.
6.3.2.5.2 Ivabradine
Several studies have shown a compelling correlation between elevated HRs and
both all-cause as well as CV mortality in the general population251,252 and CAD
patients.253,254 This relationship is independent of other risk markers.
HR reduction may reduce angina by reducing myocardial oxygen consumption and

by increasing diastolic perfusion time.
Ivabradine is a first in its class of agent that acts primarily on the SA node via
blockade of the ‘funny’ If current. It achieves HR reduction without significant
negative inotropic effect and other adverse effects associated with beta-blocker
use. Common side effects include sinus bradycardia255 and reversible visual
disturbances.256 There is no significant interaction with various cardiac drugs eg.
ACEIs, ARBs, warfarin, amiodarone, anti-platelet agents, cholesterol lowering
agents, digoxin and diuretics.
The INITIATIVE study257 showed that ivabradine is as effective as atenolol in

improving ischaemia endpoints in patients with SAP. In the BEAUTIFUL study,258
ivabradine significantly reduced ischaemic end-points of hospitalisation for fatal
and non-fatal MI and the need for coronary revascularisation in patients with
stable CAD, moderate LV dysfunction and HR>70 bpm.
Ivabradine may be considered for symptomatic treatment of SAP in patients with

normal sinus rhythm, especially in those who have a contraindication to or
intolerance to beta-blockers. It may also be used in combination with beta-
blockers in patients whose resting HR remains high.259
28
6.3.2.5.3 Non-dihydropyridine Calcium antagonist (CCB)
HR-lowering CCBs – diltiazem and verapamil may be used as an alternative to
beta-blockers in patients without CHF who do not tolerate beta-blockers.
The APSIS trial comparing metoprolol CR against verapamil SR showed similar CV

event rates in both groups of patients with SAP especially in females without
DM.27
6.3.2.6 Calcium channel blockers (CCBs)

CCBs act by blocking calcium channels in muscle cells of the heart and blood
vessel, resulting in vasodilatation, increasing coronary blood flow and decreasing
the myocardial oxygen demand. The non-dihydropyridine CCBs have an additional
effect of reducing HR.
Randomised clinical trials comparing CCB and beta-blockers have demonstrated

that CCB are generally as effective as beta blockers in relieving angina and
improving exercise time to onset of ischaemia or angina.61
6.3.2.6.1 Dihydropyridine CCB
Earlier trials of short acting nifedipine showed no prognostic benefit regarding in

CAD patients. In the ABCD260 trial, the use of nisoldipine, a short acting
dihydropyridine CCB, was associated with a higher incidence of fatal and nonfatal
MI compared with enalapril. A meta-analysis of 16 trials using immediate release
and short acting nifedipine in MI and UA reported a dose related influence on
excess mortality.261 The use of short acting dihydropyridine CCB as monotherapy is
discouraged.261-263
Long acting dihydropyridine CCB may be safe as shown in the ACTION trial, with
less coronary interventions in the CCB group but no reduction in the composite
endpoints of death, MI, refractory angina, debilitating stroke CHF.264
6.3.2.6.1 Non-dihydropyridine Calcium antagonist

See section 6.3.2.5.3
6.3.2.7 Nitrates
Nitrates are both venous and arterial dilators. It reduces myocardial oxygen demand
via its reduction of LV volume and arterial pressure via preload reduction.265,266 The
vasodilatory effect on epicardial arteries and collateral vessels improves the oxygen
supply.
The clinical benefits of nitrates are mainly seen in symptom improvement eg.
reduction of angina episodes, improvement in exercise tolerance and increase in time
to onset of ischaemia.267-270 It has no prognostic benefit.
Rapidly acting formulation of nitroglycerin provides effective symptoms relief of

angina pectoris and maybe used for situational prophylaxis.271,272
29
The anti-ischaemic effect is additive when used in combination with other anti-
anginal medications eg. beta-blockers and CCB.273
Long-acting nitrates reduces the frequency and severity of anginal attacks and may
increase exercise tolerance. These drugs failed to show prognostic benefit and are
only for symptomatic relief of angina, eg. isosorbide-5-mononitrate. The long acting-
nitrates come in tablet, transdermal patch and ointment formulations.
Nitrate tolerance may develop if used continuously resulting in breakthrough angina.

Hence, nitrate-free periods (8-12 hours) are encouraged. Rebound angina may happen
during this nitrate-free interval.
Nitrates should be used with caution in patients with severe hypertrophic obstructive
cardiomyopathy and severe aortic stenosis. PDE5-inhibitor use is contraindicated in
patients who are on nitrate therapy.274 The most common side-effect is headache.
6.3.2.8 Trimetazidine
Trimetazidine inhibits 3-KAT (3-ketoacyl CoA thiolase) enzyme in myocardial cells.

This optimises cardiac metabolism by switching energy substrate preference from
fatty acid oxidation to glucose oxidation which is a more efficient pathway for ATP
production. This promotes a favourable demand versus (vs) supply balance in
myocardial oxygen need.
Trimetazidine has been shown to be effective in providing angina symptom relief,

reduction in the need for nitrates and improving functional capacity in patients with
angina. It is useful whether as monotherapy or in combination with other anti-
ischaemic agents.275-278
It is also safe and effective in patients with ED. Therefore, it allows angina symptom
relief and concomitant treatment with PDE5-inhibitor for the Erectile Dysfunction
(ED).279
Recommendations for pharmacological therapy to improve prognosis in SAP

Aspirin 75 mg daily in all patients, if not contraindicated I, A
Clopidogrel as alternative to those intolerant to Aspirin IIa, B
ACEIs in CAD patients with other indications for ACEIs (HPT, HF, LVD, I, A
prior MI with LVD, DM)
ACEIs in all CAD patients with preserved LV systolic function IIa, B
Oral beta-blockers (Bisoprolol, Carvedilol, Metoprolol) in post MI or I, A
CHF
Statins for all CAD patients I, A
High dose statins in high risk patients IIa, B
Fibrate or nicotinic acid as adjunct to statin for improvement of non IIb, C
LDL-C fractions
30
Recommendations for pharmacological therapy to improve symptoms and or
reduce ischaemia in patient with SAP
Short acting nitroglycerin for acute treatment / situational prophylaxis I, B
Beta1-blocker: titrate according to symptoms and HR II, A
If intolerant to beta-blocker, attempt monotherapy with
• Non-dihydropyridine CCB I, A
• Long acting nitrates I, C
• Ivabradine IIa, B
If beta-blockers monotherapy insufficient add
• Long acting dihydropyridine CCB I, B
• Ivabradine IIa, B
Trimetazidine (add on / substitution) IIb, B
6.3.3 Other medical therapy

6.3.3.1 NSAIDS and COX 2 inhibitors
NSAIDS and selective COX 2 inhibitors may increase the risk of CV complications.
They should be used in the lowest effective dose and for the shortest possible
duration. If analgesia is needed, it is recommended to use Non NSAIDS analgesics
eg. paracetamol or opiates. If NSAIDS and COX 2 are unavoidable, they should be
used in combination with low dose Aspirin.
6.4 Myocardial Revascularisation

Revascularisation in patients with stable CAD confers prognostic benefit in the
following high risk group of patients, and therefore should be considered as a first
line treatment, along with optimal medical therapy.165,280
1. Significant Left main stem (LMS) disease (>50% stenosis).

2. Significant proximal multi-vessel disease with angina symptoms or in which
large area of ischaemia has been demonstrated on functional testing
3. Multi-vessel disease with impaired LV function with proven viable
myocardium
In all other conditions, revascularisation may be offered following failure of

optimal medical therapy to control symptoms.281,282 In asymptomatic patients,
revascularisation may be offered in the presence of extensive inducible ischaemia
or viable myocardium on functional tests.283
Revascularisation in patients with stable CAD may be accomplished by

• Percutaneous Coronary Intervention (PCI)
• Coronary Artery Bypass Grafting (CABG)
31
6.4.1 Percutaneous Coronary Intervention (PCI)
PCI is established as the less invasive procedure compared to CABG with lower
procedure-related mortality (0.3-1.0%). The advance in drug-eluting stents (DES)
has led to improved long-term results. Reported rate of 9-month major adverse
cardiac events range between 7.1 to 10.3 % in patients treated with DES, in
contrast to bare metal stents rate between 13.3 to 18.9%.284-286 There has been
some concern regarding the safety of DES, in particular late stent thrombosis.287
However, Sheishahbor et al. reported in a prospective PCI patient registry at
Cleveland Clinic involving over 8 000 patients implanted with DES or bare metal
stent (BMS), there was a significantly lower mortality in DES group (8% vs 17%) at
an average follow-up of 4.5 years.288 This recent findings served as a reassurance
on the safety of DES, though experts still advise caution on the small but real risk
of late stent thrombosis.289
6.4.2 Coronary Artery Bypass Grafting (CABG)

CABG is known for its long-term established data on outcome in the above high risk
groups especially in the presence of DM or concurrent valvular disease. This is
particularly true when arterial grafts are used. Typically, the internal mammary
graft has patency rate of about 90% at ten years post-CABG. As for vein grafts, the
patency rate ranges between 60-70% at 10 years. Patients who are deemed
suitable for surgery must be thoroughly evaluated and informed of the risk. In
uncomplicated patients with normal LV function and no other co-morbidity, the
reported mortality rate is under 3%.290-292
6.4.3 PCI vs CABG

Meta-analysis comparing PCI with CABG demonstrated similar mortality rates in
both groups. In the CABG group, there was a significantly higher proportion of
patients who remained symptom-free. There was also lower requirement for
repeat revascularisation.293 The BARI trial showed significantly lower 5-year
mortality in diabetics undergoing CABG compared to PCI.294 Recent Registry Data
(New York State) comparing DES vs CABG also showed a mortality difference in
favour of CABG in patients with multi-vessel disease.295 SYNTAX randomised 1,800
patients with documented multi-vessel CAD including LM stenosis to CABG or PCI.
One year follow-up from the study demonstrated comparable outcomes in
composite end points between the two strategies including the subset of patients
with LMS. PCI resulted in a higher rate of repeat revascularisation (13.7% vs 5.9%).
CABG resulted in a higher rate of stroke (2.2% vs 0.6%).296
Evidence is now emerging regarding efficacy and safety of LMS stenting,

particularly with DESs. In low risk patients with ostial or body of LMS stenosis, PCI
may be offered as an alternative (IIb, B).297,298 In LMS bifurcation, CABG should be
preferred except when patients refused surgery following thorough explanation, or
when the risk of surgery is unacceptable. Overall, there is still limited long-term
data regarding PCI in LMS. Therefore, PCI of LMS cannot be routinely
recommended. In patients with significant LMS disease who decline surgery (after
a thorough consultation), PCI with complete revascularisation may be offered. PCI
of LMS should only be carried out at experienced centre by experienced
interventional cardiologists.
32
In all cases of decision making in revascularisation, centre expertise in PCI and
CABG procedure must be taken into account with the emphasis on collaboration
between cardiologists and cardiothoracic surgeon. Prior to revascularisation
procedures, patients must be thoroughly informed of the associated risk of
mortality and morbidity, as well as long-term results.19
It should be emphasised that optimal medical therapy should be offered to all

patients regardless whether or not they undergo revascularisation. In patients who
have undergone PCI, antiplatelet therapy should be maintained according to the
standard guidelines.288
The following table summarises the recommendations:281,282,293,299,300
For For
Indication for PCI
symptom prognosis
Angina with one vessel disease I, A
Angina with multi-vessel disease (non-DM) I, A
Angina with minimal symptom but inducible ischaemia proven IIb, B
For For
Indication for CABG symptom prognosis
Angina with LMS disease I, A I, A
Angina with 3VD and:
1) Inducible ischaemia or
2) Poor LV function or I, A I, A
3) Involving proximal LAD
Angina and multi-vessel disease (DM) I, A IIa, B
Angina and multi-vessel disease (no DM) I, A
6.4.4 Revascularisation vs medical therapy

Review of data from earlier trials suggested that whenever revascularisation was
compared to optimal medical therapy, there were no significant difference in the
outcome, with the exception of CABG in diabetic patients with multi-vessel
disease.294,301,302 Two recently published trials have again reaffirmed the
importance of optimal medical therapy. COURAGE trial concluded that initial
strategy of PCI in patients with proven coronary artery disease did not provide
incremental clinical benefit over optimal medical therapy.281 BARI 2D trial in
diabetic patients with multi-vessel disease concluded that medical therapy offered
similar survival advantage comparing to revascularisation; with the only exception
of CABG – showing lower incidents of non-fatal reinfarction.303
This data provides strong evidence on the importance of optimal medical therapy
in all CAD patients – which should include antiplatelet, statin, betablocker and
RAAS inhibitor. In a majority of patients optimal medical therapy is an excellent
initial treatment strategy, particularly those with less severe disease.
33
6.5 Special Subgroups
6.5.1 Women
6.5.2 Diabetes Mellitus
6.5.3 Elderly
6.5.4 Chronic Refractory Angina
6.5.1 Women
CVD is the main cause of death among women both worldwide and in Malaysia. In
Malaysia it accounts for 25% of all female deaths in government hospitals.304
There are also numerous differences in the epidemiology of CAD between men and
women. There is a significantly lower age-specific risk of CAD in women than men.
Risk of death due to CAD in women is roughly similar to that of men 10 years
younger. Despite their marked advantage in age-specific risk of CAD death, the
greater likelihood of survival of women to advanced ages produces nearly equal
numbers of actual deaths due to CAD in men and women.
SAP is the most common presentation in women as compared to ACS and sudden
death in men.10, 305 However, women suffering from MI have a higher mortality and
morbidity compared to men. This poorer prognosis is most likely due to severity of
illness, increased age at presentation, and co-morbidity in women. In-hospital
mortality was 13% for women vs 7% for men. Cumulative mortality at 48 months
was 36% for women vs 21% for men.306
6.5.1.1 Clinical Evaluation
Evaluation of chest pain in women is less straightforward due to:
• Gender differences in presentation and disease manifestation

• SAP most frequent initial manifestation of CAD in women
• MI or sudden death is the most frequent initial manifestation in men
• Incidence of angina in women higher than men in post-menopausal age
group
• Incidence of fatal CAD higher in men with angina than women with angina
• Preponderance of male specific data in literature
6.5.1.2 Diagnosis
6.5.1.2.1 Clinical evaluation
The diagnosis of angina in women is more difficult for the following reasons:
• Atypical symptoms are more common in women
• Correlation between symptoms and ‘significant’ luminal obstruction at
coronary angiography is weaker in women
• Angina may be associated with ischaemia in Syndrome X, in the absence of
obstructive coronary lesion
• Microvascular disease and coronary vasospasm are more common in women
• Ischaemia may be shown by ECG, perfusion study or other methods in these
patients
34
6.5.1.2.2 Stress Testing
• Exercise ECG testing has higher false positive rates in women (38-67%) than
in men (7-44%)57
• However exercise ECG testing has lower false-negative rates in women
resulting in a higher negative predictive value
• Only 30% of women need to be referred for further testing
• Stress echo is an independent predictor of cardiac events in women with
known or suspected CAD
• Sensitivity of Thallium radionuclide perfusion scan may be lower in women
These patients may respond to anti-ischaemic therapy without angiographic

evidence of epicardial stenosis
6.5.1.3 Treatment
• Women tend to present at an older age and have a higher morbidity and
mortality after MI than men
• Less vigorous treatment in women may impact on reduced survival
• Women should be treated no less aggressively than men
(For further information, please refer to Clinical Practice Guidelines on Prevention of

Cardiovascular Disease in Women 2008)307
6.5.2 Diabetes Mellitus (DM)

Diabetes Mellitus (DM) is associated with increase risk of CVD. CAD mortality is
increased by three fold in diabetic men and two to five fold in diabetic women.
33,308-310
Prevalence of asymptomatic ischaemia is increased in patient with DM.311
Symptoms occur at an earlier age in diabetics. In symptomatic diabetic patients,

risk stratification strategy should follow that of non-diabetics. Diabetics may have
subclinical ventricular dysfunction which negatively impacts on exercise
capacity.312
In patients with diabetes, the higher the blood glucose the greater the incidence
of CVD.313,314 There is firm evidence of prognostic power of perfusion imaging in
diabetic patients.315
Conventional therapies for CAD are indicated with nitrates, beta-blockers, CCBs,
statins, anti-platelets and coronary revascularisation have similar indications in
diabetic and non-diabetic patients19
Due to the chronic metabolic disturbances, patients have continuous progression

of native atherosclerotic disease. This leads to extensive CAD with high rates of
multi-vessel disease and restenosis.316,317
35
DM management should include:
• lifestyle and pharmacotherapy measures to achieve a near-normal HbA1c (I,
B)230
• long-term maintenance of near-normal blood glucose levels which
substantially reduces complications and mortality in both DM types318-321
• vigorous modification of other risk factors (eg physical activity, weight
management, BP control, and cholesterol management) (I, B)230
• ACEI unless contraindicated (I, A)113
Even after successful invasive procedures, good management of CVD risk factors
and a tight glycaemic control are essential for good long-term outcome.310
6.5.3 Elderly
After the age of 75 there is equal prevalence of CAD in men and women.322
Complaints of chest discomfort, weakness and dyspnoea are common and

evaluation of chest pain can be difficult. Co-morbidities that mimic SAP are
common (eg. gastroesophageal reflux disease)
6.5.3.1 Exercise Stress ECG in the elderly

• Exercise testing may be problematic due to muscle weakness and
deconditioning
• Less challenging exercise stress ECG protocols may be more appropriate323
• Arrhythmias are more common at higher exercise stress ECG workload324
• Higher false negative due to higher prevalence of disease
• Higher false positive due to higher prevalence of confounders including prior
MI, conduction disturbances, HPT and LVH from valvular diseases.
However exercise testing remains important in the elderly despite these

differences.
6.5.3.2 Coronary Angiography

• Elderly patients with objective evidence of moderate to severe ischaemia at
non-invasive testing should have similar access to coronary arteriography as
younger patients19
• Diagnostic coronary arteriography has relatively little increased risk in
elective evaluation104
• The disease is more likely to be diffuse and severe
• LMS stenosis, 3VD and impaired LV function are more prevalent.
• Age>75 yrs is an important predictor of contrast-induced nephropathy325
6.5.3.3 Treatment
Issues in medical treatment are dose modification, drug interactions,
polypharmacy and compliance.326 Elderly patients have the same benefit from
medical therapy, angioplasty and bypass surgery as younger patients.327-329
Management of the elderly should be individualised taking into account co-

morbidities and not based on age alone.
36
6.5.4 Chronic refractory angina
Chronic stable refractory angina can be defined as a clinical diagnosis based on the
symptoms of SAP, caused by ischaemia due to advanced CAD which is not
controlled by a combination of maximal medical therapy, CABG and PCI.
Most common reasons why revascularisation is not considered:
• Unsuitable anatomy
• One or several previous CABG and/or PCI
• Lack of available graft conduits
• Extra-cardiac diseases with increased perioperative morbidity and mortality
• Advanced age, in combination with the above factors
Treatment requires optimisation of medical treatment including the use of

different drugs in maximal tolerated doses.
New treatment modalities under extensive evaluation:

• Neuromodulation techniques (transcutaneous electric nerve stimulation and
spinal cord stimulation)
• Thoracic epidural anaesthesia
• Endoscopic thoracic symphathectomy
• Stellate ganglion blockade
• Angiogenesis
• Enhanced external counterpulsation (EECP)
• Extracorporeal shockwave myocardial revascularization (ESMR)
• Transmyocardial (TMR) or percutaneous laser revascularisation
• Heart transplantation
• Drugs that modulate metabolism
Neuromodulation techniques have a favourable analgesic effect with increased

exercise time on treadmill but the clinical trials are small and long-term effects
unknown.330-332
EECP has been evaluated for safety and effectiveness in two multi-centre
registries and anginal symptoms improved in 75-80% of patients.333-335
ESMR has also been evaluated for safety and symptom relief in a few small studies
with promising results.336,337
TMR shown conflicting results in various studies with a recent randomised

controlled trial showing not benefit338 and no evidence of increased perfusion by
PET in another study.339
Chelation therapy (intravenous infusion of ethylenendiamine tetraacetic acid or

EDTA is not recommended for the treatment of chronic angina or atherosclerotic
cardiovascular disease and may be harmful because of its potential to cause
hypocalcaemia.340
37
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64
Appendix 1
Table 11. Probability of coronary disease in symptomatic patients based on (a)
age, gender, and symptom classification and (b) modified by exercise
test result264341
(a) Pre-test likelihood of CAD in symptomatic patients according to age and sex
Typical angina Atypical angina Non-anginal chest pain
Age (years)
Male Female Male Female Male Female
30-39 69.7 ± 3.2 25.8 ± 6.6 21.8 ± 2.4 4.2 ± 1.3 5.2 ± 0.8 0.8 ± 0.3
40-49 87.3 ± 1.0 55.2 ± 6.5 46.1 ± 1.8 13.3 ± 2.9 14.1 ± 1.3 2.8 ± 0.7
50-59 92.0 ± 0.6 79.4 ± 2.4 58.9 ± 1.5 32.4 ± 3.0 21.5 ± 1.7 8.4 ± 1.2
60-69 94.3 ± 0.4 90.1 ± 1.0 67.1 ± 1.3 54.4 ± 2.4 28.1 ± 1.9 18.6 ± 1.9
(b) CAD post-test likelihood (%) based on age, sex, symptom classification, exercise-induced
electrocardiographic ST-segment depression
Typical Atypical Non-anginal chest
Age ST-Depression Asymptomatic
angina angina pain
(years) (mv) Male Female Male Female Male Female Male Female
30-39 0.00-0.04 25 7 6 1 1 <1 <1 <1

0.05-0.09 68 24 21 4 5 1 2 4
0.00-0.14 83 42 38 9 10 2 4 <1
0.00-0.19 91 59 55 15 19 3 7 1
0.00-0.24 96 79 76 33 39 8 18 3
> 0.25 99 93 92 63 68 24 43 11
40-49 0.00-0.04 61 22 16 3 4 1 1 <1
0.00-0.09 86 53 44 12 13 3 5 1
0.00-0.14 94 72 64 25 26 6 11 2
0.00-0.19 97 84 78 39 41 11 20 4
0.00-0.24 99 93 91 63 65 24 39 10
> 0.25 >99 98 97 86 87 53 69 28
50-59 0.00-0.04 73 47 25 10 6 2 2 1
0.00-0.09 91 78 57 31 20 8 9 3
0.00-0.14 96 89 75 50 37 16 19 7
0.00-0.19 98 94 86 67 53 28 31 12
0.00-0.24 99 98 94 84 75 50 54 27
> 0.25 >99 99 98 95 91 78 81 56
60-69 0.00-0.04 79 69 32 21 8 5 3 2
0.00-0.09 94 90 65 52 26 17 11 7
0.00-0.14 97 95 81 72 45 33 23 15
0.00-0.19 99 98 89 83 62 49 37 25
0.00-0.24 99 99 96 93 81 72 61 47
> 0.25 >99 99 99 98 94 90 85 76
65
Appendix 2
Recommendations for routine non-invasive investigations in evaluation of SAP

Test For For prognosis
diagnosis
Laboratory tests
Full blood count, creatinine I, C I, B
Fasting glucose I, B I, B
Fasting lipid profile I, B I, B
hs-CRP, homocysteine, lp(a), ApoA, ApoB IIb, B IIb, B
ECG
Initial evaluation I, C I, B
During episode of angina I, B
Routine periodic ECG on successive visits IIb, B IIb, C
Ambulatory ECG monitoring
Suspected arrhythmia I, B
Suspected vasospastic angina IIa, C
Suspected angina with normal exercise test IIa, C
CXR
Suspected CHF or abnormal cardiac auscultation I, B I, B
Suspected significant pulmonary disease I, B
Echocardiogram
Suspected heart failure, abnormal auscultation, I, B I, B
abnormal ECG, Q waves, BBB, marked ST-changes
Previous MI
HPT or DM I, B
Intermediate or low risk patient not due to have I, C I, B/C
alternative assessment of LV function IIa, C
Exercise ECG
First line for initial evaluation, unless unable to I, B I, B
exercise/ECG not evaluable
Patients with known CAD and significant deterioration I, B
in symptoms
Routine periodic testing once angina controlled IIb, C IIb, C
Exercise imaging technique (echo or radionuclide)
Initial evaluation in patients with uninterpretable ECG
Patients with non-conclusive exercise test (but I, B I, B
adequate exercise tolerance)
Angina post-revascularisation I, B I, B
To identify location of ischaemia in planning
revascularisation IIa, B IIa, B
Assessment of functional severity of intermediate IIa, B
lesions on arteriography
IIa, C
Pharmacological stress imaging technique
Patients unable to exercise I, B I, B
Patients with non-conclusive exercise test due to poor I, B I, B
exercise tolerance
To evaluate myocardial viability IIa, B
Other indications as for exercise imaging where local IIa, B IIa, B
facilities favour pharmacological rather than exercise
stress
Non-invasive CT arteriography
Patients with low probability of disease and non- IIb, C
conclusive or positive stress test
66
Appendix 3
The following free text terms or MeSH terms (in alphabetical order) were used either
singly or in combination:
“3-KAT inhibitor”, “adrenergic beta-antagonist”, “ambulatory electrocardiographic

monitoring”, “angina pectoris review”, “angina pectoris review”, “angina pectoris”,
“angina”, “Angiogenesis”, “angiography”, “angioplasty”, “Angiotensin Converting Enzyme
inbitors”, “Angiotensin Receptor Blocker”, “anticoagulant”, “anti-oxidants”,
“anti-thrombotic agent”, “ApoA”, “ApoB”, “aspirin”, “bare metal stents”, “behaviour
modification”, “CABG”, “calcium channel blocker”, “cardiac magnetic resonance
imaging”, “cardiac nuclear scan”, “care management”, “chest pain”, “chest X-Ray”,
“chronic refractory angina”, “chronic stable angina pectoris”, “chronic stable
angina”, “clinical evaluation”, “co-morbidity”, “coronary angiography”, “coronary
arteriography”, “coronary artery bypass grafting”, “coronary artery disease”,
“Cyclooxygenase-1 inhibitors”, “definition of angina pectoris”, “definition”,
“diabetes mellitus”, “diagnosis and assessment”, “diagnosis”, “dietary modification”,
“dietary supplement”, “dipyridamole stress echo”, “dipyridamole”, “disease
management”, “dobutamine stress echo”, “drug eluting stents”, “drug therapy”,
“Drugs that modulate metabolism”, “Duke treadmill score”, “echocardiography”,
“EECP”, “elderly”, “electrocardiography”, “electron beam computed tomography”,
“EBCT”, “Endoscopic thoracic symphathectomy”, “Enhanced external
counterpulsation”, “erectile dysfunction”, “ESMR”, “exercise stress test”,
“Extracorporeal shockwave myocardial revascularization”, “GTN”, “guidelines for the
management of patients with chronic stable angina”, “health supplements”, “Heart
transplantation”, “holter electrocardiographic monitoring”, “homocysteine”, “hs-
CRP”, “Hydroxy Methyl Glutaryl-CoA reductase inhibitors”, “hypertension”, “If
inhibitor”, “invasive procedures”, “ischaemia”, “ivabradine”, “left main stem
disease”, “lifestyle modification”, “lp(a)”, “medication therapy management”,
“multislice computed tomography”, “multi-vessels disease”, “myocardial
infarctions”, “myocardial perfusion scintigraphy”, “Neuromodulation techniques”,
“nitrates”, “nitroglycerin”, “non-invasive cardiac investigation”, “omega-3 fatty
acids”, “pathophysiology”, “patient care management”, “PCI”, “percutaneous
coronary intervention”, “percutaneous laser revascularisation”, “pharmacological
stress echocardiography”, “physician support system”, “platelet aggregation
inhibitors”, “prognosis”, “revascularisation”, “risk management”, “risk
stratification”, “special subgroup”, “stable angina pectoris review”, “stable angina
pectoris review”, “stable angina pectoris”, “statin”, “stellate ganglion blockade”,
“stress cardiac magnetic resonance imaging”, “stress echocardiography”, “stress
perfusion scintigraphy”, “stress test”, “thallium myocardial perfusion scan”,
“thallium scintigraphy”, “thienopyridines”, “thoracic epidural anaesthesia”,
“transcutaneous electric nerve stimulation and spinal cord stimulation”,
“transmyocardial”, “treadmill”, “treatment modalities”, “trimetazidine”, “unstable
angina”, “women”
67
ABBREVIATION
2VD two-vessel disease
3-KAT 3-keoacyl CoA thiolase
3VD three-vessel disease
ACC American College of Cardiology
ACEI angiotensin converting enzyme-inhibitor
ACS acute coronary syndrome
ADP adenosine diphosphate
AF atrial fibrillation
AHA American Heart Association
ARB angiotensin receptor blocker
BMI body mass index
BMS bare metal stent
BP blood pressure
CABG coronary artery bypass graft
CAD coronary artery disease
CCB calcium channel blocker
CCS Canadian Cardiovascular Society
CHF congestive heart failure
CMR cardiac magnetic resonance
COX-1 cyclooxygenase 1
CPG clinical practice guidelines
CV cardiovascular
CVD cardiovascular disease
CXR chest X-ray
DES drug eluting stent
DM diabetes mellitus
DTS Duke treadmill score
EBCT Electron Beam Computed Tomography
ECG electrocardiography
Echo echocardiography
ED erectile dysfunction
EECP enhanced external counterpulsation
ESC European Society of Cardiology
FFR fractional flow reserve
GTN nitroglycerin
HOCM hypertrophic obstructive cardiomyopathy
HPT hypertension
HTA Health Technology Assessment
HR heart rate
68
IHD ischaemic heart disease
IVUS intravascular ultrasound
LAD left anterior descending artery
LBBB left bundle branch block
LMS left main stem
LV left ventricle
LVD left ventricular dysfunction
LVEF left ventricular ejection fraction
LVH left ventricular hypertrophy
MET metabolic equivalent
MI myocardial infarction
MOH Ministry of Health
MSCT multislice computed tomography
PCI percutaneous coronary intervention
PDE-5 phosphodiesterase-5 inhibitor
PVD peripheral vascular disease
QoL quality of life
RAAS renin-angiotensin-aldosterone system
SA sinoatrial
SAP stable angina pectoris
SBP systolic blood pressure
SPECT single-photon emission computed tomography
TMR transmyocardial revascularisation
TTS transdermal therapeutic system
UA unstable angina
Vs versus
WPW Wolff-Parkinson-White syndrome
69
ACRYNOMS
ABCD trial Appropriate Blood pressure Control in Diabetes trial
ACTION trial A Coronary disease Trial Investigating Outcome with
Nifedipine GITS
APSIS trial Angina Prognos Studien I Stockholm
BARI 2D trial Bypass Angioplasty Revascularization Investigation 2
Diabetes trial
BARI trial Bypass Angioplasty Revascularization Investigation trial
BEAUTIFUL study MorBidity mortality EvAlUaTion of the If inhibitor ivabradine
in patients with coronary artery disease and left ventricULar
dysfunction study
CASS registry Coronary Artery Surgery Study registry
COURAGE trial Clinical Outcomes Utilizing Revascularization and AGgressive
drug Evaluation trial
EUROPA trial EURopean trial on reduction Of cardiac events with
Perindopril in stable coronary Artery disease
HOPE trial Heart Outcomes Prevention Evaluation trial
HPS trial Heart Protection Study
INITIATIVE study INternatIonal TrIal of the AnTianginal Efficacy of IVabradinE
NCEP ATP III guidelines National Cholesterol Education Program Adult Treatment
Panel III Guidelines
ONTARGET Ongoing Telmisartan Alone and in combination with Ramipril
Global Endpoint Trial
PEACE trial Prevention of Events with Angiotensin Converting Enzyme
inhibition trial
SAPAT trial Swedish Angina Pectoris Aspirin Trial
SYNTAX SYNergy between percutaneous coronary intervention with
TAXus and cardiac surgery
TRANSCEND trial Telmisartan Randomised AssessmeNt Study in ACE-iNtolerant
subjects with cardiovascular Disease
70
ACKNOWLEDMENT
The committee of this guideline would like to express their gratitude and appreciation
to the following for their contribution:
• European Society of Cardiology (of which the National Heart Association of

Malaysia is an affiliate member) – for allowing the Committee to adopt the
European Society of Cardiology (ESC) Guidelines on the Management of
Stable Angina, 2006 as a basis for these guidelines
• Panel of external reviewers who reviewed the draft
• Technical Advisory Committee, Clinical Practice Guidelines, Ministry of Health

for their valuable input and feedback
• Health Technology Assessment Section, Ministry of Health
STATEMENT OF DISCLOSURE
The panel members have completed disclosure forms. No member holds shares in
pharmaceutical firms or acts as consultants to such firms. Details of the disclosure are
available upon request from the CPG Secretariat.
SOURCES OF FUNDING
This CPG was made possible by an unrestricted educational grant from Servier (M) Sdn
Bhd. However, the views or interests of the funding body have not influenced in any
way the contents of this CPG.
71

Management of Stable Angina Pectoris

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CLINICAL PRACTICE GUIDELINES

STABLE ANGINA PECTORIS

MOH Academy of NHAM

MEMBERS (In alphabetical order)

Dr. Betty Teh

Dr. Choo Gim Hooi

Dr. Haizal Haron Kamar

Dr. K. Sree Raman

Dr. Oteh Maskon

Dr. Shaiful Azmi Yahaya

Dr. Tong Seng Fah

EXTERNAL REVIEWERS (in alphabetical order)

The following external reviewers provided feedback on the draft.

Dr. Alzamani Mohammad Idrose

Dr. Chew Boon How

Dr. Kauthaman A. Mahendran

Dr. Jeyamalar Rajadurai

Dr. Shaiful Bahari Ismail

Dr. Sim Kui Hian

Dr. Wan Azman Wan Ahmad

Dr. Venugopal Balchand

Dr. Zurkurnai Yusof

In Malaysia, these patients may be managed by cardiologists, physicians and primary

Literature search was carried out at the electronic databases of PUBMED/MEDLINE,

Dr. Azani Mohd Daud

Conditions for which there is conflicting evidence and/or divergence

IIa Weight of evidence/opinion is in favor of its usefulness/efficacy

IIb Usefulness/efficacy is less well established by evidence/opinion

Non anginal chest pain* Suspected stable angina Suspected UA/ACS

Manage accordingly Refer to CPG on

Confirmed stable angina

Evaluate prognosis on basis of clinical evaluation and non-invasive tests

Low risk Intermediate risk High risk

Medical therapy Medical therapy

2. DEFINITION AND PATHOPHYSIOLOGY

Unstable Angina (UA) may present in the following ways:19

Other causes of myocardial ischaemia include:

Myocardial ischaemia is caused by an imbalance between myocardial oxygen supply

Coronary arterial flow which is dependant on luminal cross-sectional area and

Mismatch in myocardial oxygen supply and demand results in metabolic abnormalities,

Table 2. Canadian Cardiovascular Society Classification (CCS) of Angina

Annual mortality rates from clinical trial on anti-anginal therapies and or

4 DIAGNOSIS AND ASSESSMENT

4.1 Symptoms and signs

Table 3. The characteristics of discomfort related to myocardial

Table 4. Clinical classification of chest pain

Table 5. Causes of non-anginal chest pain

Unstable Angina (UA)

Physical examination is directed at:

Investigations in stable angina may be divided broadly into 5 groups:

4.2 Laboratory tests

Recommendation of laboratory investigations

Recommendations for CXR for initial diagnostic assessment of angina

4.4 Non-invasive cardiac investigations

4.4.1 Resting electrocardiography (ECG)

Recommendations for resting ECG for initial diagnostic assessment

Recommendations for resting ECG for routine re-assessment in

Recommendations for exercise ECG for initial diagnostic assessment

Recommendations for exercise ECG for routine re-assessment in

4.4.3 Stress testing in combination with imaging

Table 7. Summary of test characteristics for investigations used in the

4.4.3.1 Exercise testing with echocardiography

4.4.3.2 Exercise testing with myocardial perfusion scintigraphy