GUIDELINES FOR

MANAGEMENT OF NON ST ELEVATION

ACUTE CORONARY SYNDROME (NSTEACS)
FOR MINISTRY OF HEALTH ( MOH )
HOSPITALS & HEALTH CENTRES IN
KELANTAN.

SECOND EDITION 2012.

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PREPARED BY :

1.DR HAJI AZERIN OTHMAN.

BMBS (Flin. Sth. Aust.). MRCP (UK).
FRCP (Glasgow). FNHAM (Mal).
CONSULTANT CARDIOLOGIST.
HOSPITAL RAJA PEREMPUAN ZAINAB II,
KOTA BHARU.

2.DR HAJI MANSOR YAHYA.

MD (UKM) . MMED (USM) .
CONSULTANT CARDIOLOGIST.
HOSPITAL RAJA PEREMPUAN ZAINAB II,
KOTA BHARU.
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Table of Contents. Page.

1.0 INTRODUCTION AND BACKGROUND. 4

2.0 OBJECTIVES. 5

3.0 TRIAGE. 6

4.0 TREATMENT PROCEDURE. 7

4.1 Criteria for diagnosis of NSTEACS. 7

4.2 Management of NSTEACS on presentation 8

/ admission and risk stratification.

4.3 Management of NSTEACS: Pharmacotherapy. 15

5.0 INDICATIONS FOR CORONARY ANGIOGRAM AND 37

PERCUTANEOUS CORONARY INTERVENTION
(PCI) IN NSTEACS.

6.0 INDICATIONS FOR REFERRAL AND REFERRAL 39

CENTRES FOR STATE OF KELANTAN.

7.0 NSTEACS FLOW CHART. 40

8.0 IMPORTANT CONTACT NUMBERS. 41

APPENDICES.

Appendix 1: Diagnostic and preanticoagulant 42

checklist.

Appendix 2: Checklist for the management of 45

NSTEACS on presentation / admission.

ACKNOWLEDGEMENTS. 46

REFERENCES 47
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1.0 INTRODUCTION AND BACKGROUND.

Cardiovascular disease is the commonest cause of mortality in

government hospitals. Coronary artery disease (CAD) is the major
cause of these deaths.

In more advanced countries, mortality from heart disease has

decreased due to reduction in risk factors such as smoking and life
style changes and better management of heart disease. Much
progress has been made in the management of Acute Coronary
Syndrome (ACS) especially in the last two decades. Acute
Coronary Syndrome (ACS) encompasses ST Elevation Myocardial
Infarction (STEMI) , Non ST Elevation Myocardial Infarction
(NSTEMI) and Unstable Angina (UA).The majority of ACS cases
now are Non ST Elevation Myocardial Infarction (NSTEMI) and
Unstable Angina (UA) compared to ST Elevation Myocardial
Infarction (STEMI).The pathophysiology,clinical presentation, ECG
and treatment of Non ST Elevation Myocardial Infarction (NSTEMI)
and Unstable Angina (UA) are the same.The only difference is that
biochemical markers are elevated in NSTEMI whereas it is not
elevated or otherwise normal in Unstable Angina.Until biochemical
markers results are available, NSTEMI and Unstable Angina are
termed as Non ST Elevation Acute Coronary Syndrome
(ACS).Contrary to STEMI where events occur before or shortly
after presentation, NSTEACS events continue over days , weeks
and with repeated episodes or admissions until optimal
pharmacotherapy and revascularization procedures are instituted
or performed.

Most information in these guidelines are derived from Ministry of

Health Malaysia, The National Heart Association of Malaysia,
Academy of Medicine Malaysia . Clinical Practice Guidelines on
Management of Unstable Angina/Non_ST-Elevation Myocardial
Infarction 2011 , ACCF/AHA 2011 Guidelines for the Management of
Patients with Unstable Angina/Non_ST-Elevation Myocardial
Infarction, ESC 2011 Guidelines for the management of acute
coronary syndromes in patients presenting without persistent ST
segment elevation ,as well as other latest evidence based
information. Apart from that, all the treatment and recommendations
in these guidelines are based on drugs,treatment and facilities that
are readily available in hospitals or health centres in Kelantan. This
second edition guidelines are an updated version with new changes
compared to the first edition which was circulated in 2009.
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2.0 OBJECTIVES.

2.1 General objectives:

a) To provide knowledge and guidance in terms of management

of patients with Non ST Elevation Acute Coronary Syndrome
(NSTEACS).

b) To ensure that the patient receive early and optimal

treatment to reduce morbidity and mortality.

c) To create standard guidelines of NSTEACS treatment at all

MOH district hospitals and health centres in Kelantan.

2.2 Specific objectives:

a) To initiate treatment as early as possible.

b) To provide standard guidelines to diagnose NSTEACS , risk

stratification, as well identifying clinical parameters that are
indicators for early coronary angiogram,thus early
revascularization therapy either percutaneously or
surgically .

c) To provide standard guidelines for adjunct optimal

pharmacotherapy in the management of NSTEACS which
include indications and contraindications for such therapy,
dosage,possible complications related to the treatment as
well as monitoring of the complications.

d) To provide guidelines for referral to tertiary hospital and for

early coronary angiogram and intervention.
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3.0 TRIAGE.

EMERGENCY DEPARTMENT OF HOSPITALS.

HEALTH CARE CENTRES / CLINICS.

ACUTE CHEST PAIN OR EQUIVALENT SYMPTOMS.

PRIMARY TRIAGE BY PARAMEDIC

TYPICAL OR SUSPECT ATYPICAL OR SUSPECT

OF ACS. OF NON ACS.

SECONDARY TRIAGE BY PARAMEDIC

ABNORMAL / SUSPICIOUS ECG

NORMAL

RED ZONE / TREATMENT ROOM. YELLOW / GREEN ZONE / CLINIC.

URGENT ECG & BLOOD RELEVANT INVESTIGATIONS.
INVESTIGATIONS. REASSESS BY MO.
URGENT REVIEW & TREATMENT TRANSFER IF INDICATED.
BY MO.
TRANSFER IF INDICATED.
(WITHIN 30MIN OF PRESENTATION).

ACS - Acute Coronary Syndrome.

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4.0 TREATMENT PROCEDURE.

4.1 Criteria for Diagnosis of NSTEACS.

1.Chest pain or angina equivalent suggestive of ischaemic in

origin.

2.ECG changes : NO ST ELEVATION.

ST depression in 2 or more contiguous leads of standard 12

lead ECG 0.5mm.

Deep T wave inversion 2mm.

Minor changes or normal ECG.

3.Elevated biochemical markers (CKMB ,Troponin).

NSTEMI.

4.Normal biochemical markers (CKMB ,Troponin).

UNSTABLE ANGINA.
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4.2 Management of NSTEACS on presentation / admission and

risk stratification.

1. Initial management .
i) All case must be reviewed as soon as possible by the
admitting medical officer /specialist /consultant in
casualty,general ward or other areas before deciding to
transfer to CCU/CRW /critical care unit / other hospital
/ tertiary centre.

ii) All patients , the following investigations must be taken

immediately,if not done earlier :
FBC.
APTT, INR.
BUSE ,Serum Creatinine, LFT .
RBS.
12 lead ECG .
Cardiac enzymes : CKMB or Troponin T .
Chest radiograph.
Lipids.
Other investigations : ABG, Echocardiography when
indicated .

iii) All cases must be transferred to CCU/CRW /critical care unit

for treatment.

accompanied by doctor / paramedic .
ECG monitor / defibrillator .
at least 2 large bore IV access .
2. Risk Stratification.

i) Stratify patients : TIMI OR GRACE RISK SCORE +

CLINICAL PARAMETERS.

PREDICT LIKELIHOOD OF ACS AS THE TRUE
PRESENTATION.
PREDICT SHORT TERM ADVERSE OUTCOME.
DETERMINE TYPE OF THERAPY.

?LOW RISK : treat conservative and non invasive
tests.
?INTERMEDIATE RISK : need early intervention
and GPIIb/IIIa inhibitor.
?HIGH RISK : need early intervention and
GPIIb/IIIa inhibitor.

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TABLE 1.TYPES OF RISK SCORES USED IN CLINICAL PRACTICE

 10

TABLE 2.TIMI RISK SCORE.

1. AGE 65.

2. 3 RISK FACTORS.
( Family history, Hypertension, Hyperlipidaemia,
Diabetes Mellitus, Active smoker ).

3. KNOWN Coronary Artery Disease

( Stenosis 50% ).

4. ASPIRIN USE IN PAST 7 DAYS.

5. SEVERE ANGINA ( AT LEAST 2 ) WITHIN 24 HOUR.

6. ELEVATED CARDIAC MARKERS.

7. ECG CHANGES :ST DEVIATION 0.5mm.

TOTAL SCORE : 0 7.



RISK. SCORE. ALL CAUSE MORTALITY , NEW &
RECURRENT MI.

LOW. 0-2. 4.7% - 8.3%.

INTERMEDIATE. 3-4. 13.2% - 19.9%.

HIGH. 5-7. 26.2% - 40.9%.












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TABLE 3. GRACE RISK SCORE

FOR FURTHER DETAILS & GRACE RISK SCORE CALCULATOR GO TO

http://www.outcomes-umassmed.org/grace
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TABLE 4 : RISK STRATIFICATION COMBINING TIMI & GRACE

RISK SCORE AND CLINICAL PARAMETERS.

A.HIGH RISK NSTEACS .

Presentation with clinical features consistent with NSTEACS and

any of the following features :

1. High TIMI RISK SCORE : 5 - 7 or High GRACE RISK SCORE.

2. Repetitive or prolonged (>10 minutes) ongoing chest pain or

discomfort.

3. Elevated level of TROPONIN OR CKMB.

4. Persistent or dynamic ECG changes of ST depression 0.5 mm

or new T- wave inversion 2 mm.

5.Transient ST Segment Elevation ( 0.5 mm) in more than

two contiguous leads.

6. Haemodynamic compromise : SBP< 90 mmHg, cool peripheries,

diaphoresis, heart failure / Killip Class > I and / or new-onset
mitral regurgitation.

7. Sustained Ventricular Tachycardia.

8. Syncope.

9. Left Ventricular Systolic dysfunction (LVEF 40%).

10. Prior Percutaneous Coronary Intervention (PCI) within 6

months or prior coronary artery bypass surgery (CABG).

11. Presence of known Diabetes Mellitus.

(with typical symptoms of NSTEACS).

12. Chronic Kidney Disease ( GFR< 60 mL/minute ).

(with typical symptoms of NSTEACS).

Principle of treatment : Aggressive Medical Therapy.

+
Glycoprotein IIb / IIIa Inhibitor.
+
Early Coronary Angiogram.

Prognosis : RISK OF DEATH AND MI IN 6 MONTHS > 10%.

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B.INTERMEDIATE RISK NSTEACS.

Presentation with clinical features consistent with NSTEACS and

any of the following features :

1. Intermediate TIMI RISK SCORE:3 - 4 or Intermediate GRACE RISK SCORE.

2. Chest pain or discomfort within the past 48 hours that occurred

at rest, or was repetitive or prolonged (but currently resolved).

3. Age 65 years.

4. Known coronary artery disease - prior myocardial infarction with

LVEF > 40%, or known coronary lesion with 50% stenosis.

5. No high-risk changes on ECG AS IN HIGH RISK

6. Two or more of the following risk factors: known Hypertension,

Family history, Active smoking or Hyperlipidaemia.

7. Presence of known Diabetes Mellitus.

(with atypical symptoms of NSTEACS).

8. Chronic Kidney Disease ( GFR< 60 mL/minute ).

(with atypical symptoms of NSTEACS).

9. Prior Aspirin.

Principle of treatment : Aggressive Medical Therapy.
+
Glycoprotein IIb / IIIa Inhibitor.
+
Early Coronary Angiogram.

Prognosis : RISK OF DEATH AND MI IN 6 MONTHS
2%-10%.











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C.LOW RISK NSTEACS.

Presentation with clinical features consistent with NSTEACS and

any of the following low risk features AND NOT meeting the criteria
for high-risk or intermediate risk features NSTEACS :

1. Low TIMI SCORE : 0 - 2 or Low GRACE RISK SCORE.

2. Onset of anginal symptoms within the last month.

3. Worsening in severity or frequency of angina, or lowering of

anginal threshold.

Principle of treatment : Agressive Medical therapy.
+
Non Invasive Stratification.
+
Elective Coronary Angiogram.






Prognosis : RISK OF DEATH AND MI IN 6 MONTHS < 2%.

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4.3 Management of NSTEACS : Pharmacotherapy.

i) Oxygen .

2 L / min 4 L / min.
Generally indicated in all patients especially who are :
~ in pain.
~ breathlessness.
~ overt failure / pulmonary congestion.
~ saturation O2 < 90 %.
~ first 3 hours.
~ complicated NSTEACS.

.
ii) Analgesia .

Necessary to relieve pain promptly as it precipitates

autonomic disturbances, which can trigger malignant
arrhythmias .

IV Morphine :
~Dose : 2 - 4mg PRN, up to 8mg at interval of 5 to 15
minutes until pain completely relieved or there is
evidence of toxicity - hypotension, respiratory
depression or severe vomiting.

~Usually given with IV antiemetics :

- IV Promethazine ( Phenergan ) : 25mg - 50mg PRN.

or
- IV Metoclopramide ( Maxolon ) : 10mg PRN.

~can cause :
- hypotension when hypovolaemia or upright
position.
- worsening bradycardia.
- respiratory depression.

If worry about bradycardia, give IV Meperidine

( Pethidine) : 25mg - 50mg PRN slow bolus.
Antidote ~ IV Naloxone ( Narcan ) : 0.4mg - 0.8mg every
15 minutes ; up to max. 1.2mg to reverse morphine
effects.
Avoid intramuscular injections.
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iii) Nitrates.

Nitrates do not improve survival.

Indications :
~ persistent angina / ischaemia.
~ hypertension.
~ heart failure.

Duration : - IV nitrate : 24 - 48 hours or until pain or

complication-free

- Oral nitrate: depend clinically, not mandatory
thereafter or lifelong.

Contraindications :
~ Hypotension : SBP < 100 mmHg or 30 mmHg drop
from baseline BP
~ Bradycardia : 50 bpm.
~ Hypovolaemia.
~ Cardiac tamponade.
~ Concomitant use phosphodiesterase inhibitor such as
Sildenafil.

Common side effects :

~ headache.
~ hypotension.
~ tolerance.

If hypotension / bradycardia occurs :

Stop infusion.
Legs elevated.
Fluid administration cautiously.
IV Atropine 1mg stat if needed.

Dosage infusion of IV Nitrates :

F IV ISOKET OR GTN : 10g/min - 200g/min.

( 0.6mg/hr -12mg/hr ).

Dosage oral or other nitrates :

F S/L GTN : 0.5mg PRN.
F ORAL ISOSORBIDE DINITRATE (ISORDIL)
: 10mg - 30mg TDS.
F NITRODERM TRANSDERMAL PATCH
: 5mg for 8 - 12hr /day *

* Need 8-12hr free period to avoid tolerance.

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iv) Antiplatelets : dual antiplatelets regime.

Bolus - Aspirin 300mg + Clopidogrel 300mg.

Maintenance - as below

if for medical therapy - Aspirin 75-150mg OD + Clopidogrel

75mg OD for at least 1 month,ideally
better for 12 months then Aspirin
75-150mg OD lifelong.

if PCI within 1st year of NSTEACS - Aspirin 75-150mg OD +

Clopidogrel 75mg OD for
at least 12 month then
Aspirin 75-150mg OD
lifelong.

[ irrespective either drug eluting stent (DES) or bare metal

stent (BMS ) ]

if PCI done beyond 1year of NSTEACS - Aspirin 75-150mg

OD + Clopidogrel
75mg OD for at
least 12 months
then Aspirin
75-150mg OD
lifelong if use DES

or

- Aspirin 75-150mg
OD + Clopidogrel
75mg OD for at
least 1month then
Aspirin 75-150mg
lifelong if use BMS

NOTE :

-If patient intolerable to Aspirin due to GI upset or dyspepsia,

consider Aspirin 75mg OD or enteric coated Aspirin such as
Cardiprin 100mg OD with H2 blocker or Proton Pump Inhibitor
preferably Pantoprazole and take Aspirin / Cardiprin with meal.

-Also alternative to Aspirin 150mg is Cardiprin 100mg.

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vIf contraindicated or Aspirin allergy:

Bolus - Clopidogrel 300mg

Maintenance - as below

if for medical therapy - Clopidogrel 75mg OD lifelong.

if for PCI : need desensitization therapy to aspirin

first before embarking PCI .

If desensitization therapy successful

Proceed to PCI and regime as below
if PCI within 1st year of ACS
- Aspirin 75-150mg OD + Clopidogrel 75mg OD
for 12 month then Aspirin 75-150mg OD
lifelong.
[ irrespective either drug eluting stent (DES) or
bare metal stent (BMS ) ]

if PCI done beyond 1year of ACS

- Aspirin 75-150mg OD + Clopidogrel 75mg OD
for at least 12 months then Aspirin 75-150mg
OD lifelong if use DES
or
- Aspirin 75-150mg OD + Clopidogrel 75mg OD
for at least 1month then Aspirin 75-150mg OD
lifelong if use BMS

: otherwise if failed desensitization therapy or

unable to take dual antiplatelets

High risk stent thrombosis

Defer PCI

CABG or Medical therapy .
 19

v) Anticoagulant.

- Mandatory in NSTEACS.
- Types : Factor Xa inhibitor - Fondaparinux.
- Subcutaneous 2.5mg OD.
- This dose applied if creatinine 265mol/l.
- If creatinine > 265mol/l "half dose or use UFH.
- If creatinine clearance 30ml/min" use UFH.

OR

Low Molecular Weight Heparin ( LMWH ).

Primary choice - Enoxaparin.
- Subcutaneous 1mg/kg BD.
- This dose applied if creatinine 221mol/l(male)
or 177mol/l(female) .
- If creatinine > 221mol/l(male) or >177mol/l
(female) " half dose or 1mg/kg OD or use UFH.
- If creatinine clearance 30ml/min" use UFH.

OR

Unfractionated heparin (UFH)

- Initial : - Start with IV bolus 60 - 70unit/kg
(max:5000unit) & infusion
12 - 15unit/kg/hr (max:1000unit/ hr ).
- Monitor : 6 hourly APTT.
- Aim APTT : 1.5-2.0 X of control( 50-70s).

- Duration : UFH - at least 48 hours.

Fondaparinux - at least 48 hours up to 8 days.
Enoxaparin - at least 48 hours up to 8 days.

Note: If anticipate or plan for early/urgent coronary angiogram and

severe renal dysfunction or ESRF,CHANGE OR USE
unfractionated heparin (UFH) instead of Enoxaparin or
Fondaparinux. If for urgent PCI, DO NOT USE Fondaparinux as
high risk of catheter thrombosis.

As Enoxaparin preparation only in fixed dosages of 40mg(0.4ml)

and 60mg (0.6ml),it is cumbersome to give to patient who are
outside of this range,thus another option is to give as in venous
thromboembolism treatment which are as follows :
< 50kg : 40mg BD.
50-69kg : 60mg BD.
70-90kg : 80mg BD.
> 90kg : 100mg BD.

If still need treatment of anticoagulant beyond 48 hours , better

change to Fondaparinux or Enoxaparin as to avoid Heparin
Induced Thrombocytopaenia (HIT).
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CONTRAINDICATIONS OF ANTICOAGULANT.

Absolute Contraindications:

1. Any prior intracranial hemorrhage.

2. Known structural cerebral vascular lesion (e.g., arteriovenous
malformation).
3. Known malignant intracranial neoplasm (primary or metastatic).
4. Already significantly prolonged INR or APTT.
5. Suspected or evidence of aortic dissection.
6. Active bleeding or bleeding diathesis (excluding menses).
7. Hypersensitivity to anticoagulant.
8. Bacterial endocarditis.

Relative Contraindications:

1. Untreated bleeding disorders such as Haemophilia or other

haemorrhagic disorders.
2. Severe uncontrolled hypertension on presentation (SBP greater
than 180 mm Hg or DBP greater than 110 mm Hg).
3. Thrombocytopenia with platelets < 60,000.
4. History of heparin-induced thrombocytopenia (HIT).
5. Major surgery (within less than 3 weeks).
6. Recent (within 2 to 4 weeks) internal bleeding.
7. Noncompressible vascular punctures.
8. Other intracranial pathology not covered in absolute
contraindications.
9. Significant pericardial effusion - undrained or without regular
ultrasonographic monitoring.
10. Active peptic ulcer.
11. Liver failure or advanced liver disease.
12. Underlying malignancy.
13. Unconscious, confused, agitated.
14. Severe renal dysfunction. (Creatinine clearance < 30ml/min).
-for LMWH and Fondaparinux.
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vi) Beta-blocker ( -blocker ).

Proven in reducing mortality and as antianginal in NSTEACS.

Indicated in all patients after excluding contraindication ,start

within 24hour if possible.

Contraindications :

i) Airways disease - COAD/ Bronchial asthma.

ii) Moderate to severe heart failure.
iii) Hypotension SBP < 100 mmHg or 30 mmHg
drop from baseline BP
iv) Bradycardia < 60 bpm.
v) PR interval > 240 ms.
vi) Secondary or third degree AV block.
vii) Severe peripheral vascular disease (PVD).

Dosage :

FIf LV function good (LVEF > 40%) , use

Atenolol : 25mg -100mg OD.

or
Metoprolo l: 25mg -100mg BD.

FIf LV systolic dysfunction (LVEF 40%) , use

Bisoprolol : 1.25mg - 10mg OD.

or
Carvedilol : 3.125mg - 25mg BD.
 22

vii) ACE-inhibitor (ACE-I).

Indications : MOST BENEFIT WHEN EVIDENCE OF THE

FOLLOWINGS.
Heart failure .
LV systolic dysfunction, EF 40 %, both asymptomatic /
symptomatic.
Anterior MI.
Hypertension .
Diabetes Mellitus .
Reinfarction.
Left bundle branch block (LBBB).
Peipheral vascular disease (PVD) .
Cerebral vascular accident (CVA).

Latest recommendation : benefit in NSTEACS even EF >

40% or without any of the above features ( class IIa ) . Thus ,
ACE -I ,should be given to all patients even without the
above features .

Start within 24 hour if possible.

BENEFIT IN ALL NSTEACS PATIENTS.

Contraindications :
Allergic / intolerable / angioedema.
Hypotension SBP < 100 mmHg or 30 mmHg drop from
baseline BP.
Serum creatinine > 221mol / l* or worsening renal
function.
Renal failure not on permanent renal replacement
therapy/dialysis.
Moderate to severe valvular stenoses.
Renal artery stenoses : bilateral or unilateral with a solitary
functioning kidney.
Pregnancy and breast feeding.
Hyperkalaemia > 5.0mmol/l.
Hypovolaemia or dehydration.

Dosage : start with low dose,any of these :

- Captopril : 6.25mg BD 50mg TDS.
- Enalapril : 2.5mg BD 10mg BD.
- Perindopril : 2mg OD 8mg OD.
- Ramipril : 1. 25mg OD 10mg OD.

* Relative contraindication - acceptable up to 50% worsening of

baseline creatinine or 265 umol/l - which one is lower .
(ESC Guidelines CHF 2008).
 23

viii) Angiotensin Receptor Blocker (ARB).

Indications: ONLY if patients intolerable to ACE -I in

NSTEACS with the following features:
Heart failure .
LV systolic dysfunction, EF 40 %, both asymptomatic /
symptomatic.
Anterior MI.
Hypertension .
Diabetes Mellitus .
Reinfarction.
Left bundle branch block (LBBB).
Peripheral vascular disease (PVD) .
Cerebral vascular accident (CVA

USE IF INTOLERABLE TO ACE-I & IN SELECTED PATIENTS.

Contraindications :
Allergic / intolerable / angioedema.
Hypotension SBP < 100 mmHg or 30 mmHg drop from
baseline BP.
Serum creatinine > 221mol / l * or worsening renal
function.
Renal failure not on permanent renal replacement
therapy/dialysis.
Moderate to severe valvular stenoses.
Renal artery stenoses : bilateral or unilateral with a solitary
function kidney.
Pregnancy and breast feeding.
Hyperkalaemia > 5.0mmol/l.
Hypovolaemia or dehydration.

Dosage : can start any of these :

- Valsartan : 40mg -160mg daily.
- Losartan : 25mg -100mg daily.
- Telmisartan : 20mg - 80mg daily.
- Irbesartan : 75mg - 300mg daily.

* Relative contraindication - acceptable up to 50% worsening of

baseline creatinine or 265 umol/l - which one is lower.
(ESC Guidelines CHF 2008).
 24

ix) Statin.

Evidences have shown that statin improves outcome even

with normal cholesterol levels.

Start statin irrespective levels and life long.

Aim : TC < 4.0mmol/l. LDL < 1.8mmol/l.

TG < 1.7mmol/l. HDL > 1.1mmol/l.

Dosage: Simvastatin : 20mg - 40mg ON.

Pravastatin : 20mg - 40mg ON.
Atorvastatin :10mg - 80mg ON.
Lovastatin : 20mg - 80mg ON.
Rosuvastatin : 5mg - 20mg ON.

x) Aldosterone Antagonist.

Indications : NSTEACS with the followings

Previous STEMI* with LV EF 40% with heart failure.

Previous STEMI* with LV EF 40% with underlying DM.

Dosage : Spironolactone 25mg - 50mg OD.

Ideally should also on ACE -I / ARB and -blocker and for

life long.

Contraindicated - Hyperkalaemia > 5.0mmol/l.

- Creatinine > 221mol/l(male).
- Creatinine > 177mol/l(female).
- Creatinine clearance 30 ml/min.
- Concomitant ACE-I + ARB.

* AHA/ACC guidelines UA/NSTEMI ( 2007) also recommend in NSTEACS patient without

previous MI with LV EF 40% with heart failure or in NSTEACS patient without
previous MI with LV EF 40% with underlying DM.
 25

xi) IV GLYCOPROTEIN IIb/IIIa INHIBITORS.

- TIROFIBAN (AGGRASTAT).
- ABCIXIMAB (REOPRO)

Indications : NSTEACS with high risk features going for PCI

WITH LOW RISK BLEEDING.

NO LONGER USE SOLELY AS MEDICAL THERAPY OR

CONSERVATIVE THERAPY WITHOUT PLANNING FOR
PCI. (EARLIER TIROFIBAN WAS APPROVED FOR
MEDICAL THERAPY WITHOUT PLAN FOR PCI)

Can be used as upstream therapy i.e before coronary

angiogram & PCI or provisional therapy .i.e given after
coronary angiogram & plan for high risk PCI eg thrombus
laden lesion.

Best is as provisional therapy as LESS BLEEDING & if

indicated for CABG can proceed earlier as well less risk of
bleeding intraoperatively

Preparation for TIROFIBAN (AGGRASTAT) during PCI:

Mix 25ml ( vial) of Aggrastat in 100ml NS.

or
Mix 50ml ( 1 vial ) of Aggrastat in 200ml NS.
(discard 300ml from 500ml NS bottle.)

IV bolus over 3min or IC over 1 min based from the chart.

If indicated for IV infusion thereafter ,start IV infusion the
remained amount in preparation over 12-24 hours post
PCI or till finished based from the chart
 26

Dosage of Tirofiban (Aggrastat) for PCI.

Patient Loading Maintenance

Weight (kg). Bolus (ml). IV Infusion
IV-3min Rate
IC-1min (ml/hr).
25g/kg. 0.15g/kg/min.

30 - 37 17.5 6

38 - 45 20 8

46 - 54 25 9

63 - 70 32.5 12

71 - 79 37.5 14

80 - 87 42.5 15

88 - 95 45 17

96 - 104 50 18

105 - 112 55 20

113 - 120 57.5 21

121 - 128 62.5 23

129 - 137 65 24

138 - 145 70 26

146 - 153 75 27
 27

CONTRAINDICATIONS OF TIROFIBAN.

Known hypersensitivity to any component of the product.

Active (internal) bleeding or a history of abnormal
bleeding tendencies.
A history of intracranial hemorrhage,neoplasm, AVM or
aneurysm.
Thrombocytopenia following prior exposure to Tirofiban.
Coagulopathy, platelet disorder or thrombocytopenia <
100,000.
Stroke within 30 days - 2 years or any history of
hemorrhagic stroke.
Major surgical procedure or severe physical trauma
within 30 days.
Severe uncontrolled hypertension (SBP greater than
180mm Hg or DBP greater than 110 mm Hg).
Acute pericarditis and significant pericardial effusion.
Clinically significant liver disease.
Concomitant use of other Glycoprotein IIb/IIIa inhibitors.
Administration of warfarin within 7 days unless INR < 1.5
Pregnancy and breast feeding.
ESRF or on dialysis or serum creatinine > 350mol/l or
creatinine clearance 30ml/min.
Suspected or evidence of aortic dissection.
 28

Preparation for ABCIXIMAB (REOPRO).during PCI:

Reopro 1 vial :10mg/5ml (2 mg/mL )

Loading bolus : Dose 0.25 mg/kg.

- Withdraw indicated dose from 10 mg/5mL vial
(2mg/mL) with provided filter to syringe.

- Administer with filter IV or IC over 1 minute based from chart .

If indicated start IV infusion : Dose 0.125 mcg/kg/min
(max dose 10 mcg/min).
- Prepare 250ml NS by discarding 250ml from 500ml NS
IVD bottle.
- Withdraw indicated dose from remaining or new
10 mg/5mL vial with provided filter into the 250ml NS.
- Administer with filter IV from the 250ml NS at fixed
rate of 21ml/hr for 12 hour based from chart
 29

Dosage of Abciximab (Reopro) for PC

Patient Loading Maintenance

Weight (kg). Bolus IV or IC. IV Infusion.
___ml/mg to be ___ml/mg to be
given bolus added to 250ml NS.
over 1 min. run at 21ml/hr.

ml mg ml mg

45 5.6 11.2 2.0 4.0

46 5.8 11.6 2.1 4.2

47 5.9 11.8 2.1 4.2

48 6.0 12.0 2.2 4.4

49 6.1 12.2 2.2 4.4

50 6.3 12.6 2.3 4.6

51 6.4 12.8 2.3 4.6

52 6.5 13.0 2.3 4.6

53 6.6 13.2 2.4 4.8

54 6.8 13.6 2.4 4.8

55 6.9 13.8 2.5 5.0

56 7.0 14.0 2.5 5.0

57 7.1 14.2 2.6 5.2

 30

Dosage of Abciximab (Reopro) for PCI (cont.).

Patient Loading Maintenance

Weight Bolus IV or IC. IV Infusion.
(kg). ___ml/mg to be ___ml/mg to be
given bolus added to 250ml NS.
over 1 min. run at 21ml/hr.

ml mg ml mg

58 7.3 14.6 2.6 5.2

59 7.4 14.8 2.7 5.4

60 7.5 15.0 2.7 5.4

61 7.6 15.2 2.7 5.4

62 7.8 15.6 2.8 5.6

63 7.9 15.8 2.8 5.6

64 8.0 16.0 2.9 5.8

65 8.1 16.2 2.9 5.8

66 8.3 16.6 3.0 6.0

67 8.4 16.8 3.0 6.0

68 8.5 17.0 3.1 6.2

69 8.6 17.2 3.1 6.2

70 8.8 17.6 3.2 6.4

 31

Dosage of Abciximab (Reopro) for PCI (cont.).

Patient Loading Maintenance

Weight (kg). Bolus IV or IC. IV Infusion.
___ml/mg to be ___ml/mg to be
given bolus added to 250ml NS.
over 1 min. run at 21ml/hr.

ml mg ml mg

84 10.5 21.2 3.6 7.2

85 10.6 21.2 3.6 7.2

86 10.8 21.6 6.6 7.2

87 10.9 21.8 3.6 7.2

88 11.0 22.0 3.6 7.2

89 11.1 22.2 3.6 7.2

90 11.3 22.6 3.6 7.2

91 11.4 22.8 3.6 7.2

92 11.5 23.0 3.6 7.2

93 11.6 23.2 3.6 7.2

94 11.8 23.6 3.6 7.2

95 11.9 23.8 3.6 7.2

96 12.0 24.0 3.6 7.2

97 12.1 24.2 3.6 7.2

 32

Dosage of Abciximab (Reopro) for PCI (cont.).

Patient Loading Maintenance

Weight (kg). Bolus IV or IC. IV Infusion.
___ml/mg to be ___ml/mg to be
given bolus added to 250ml NS.
over 1 min. run at 21ml/hr.

ml mg ml mg

98 12.3 24.6 3.6 7.2

99 12.4 24.8 3.6 7.2

100 12.5 25.0 3.6 7.2

101 12.6 25.2 3.6 7.2

102 12.8 25.6 3.6 7.2

103 12.9 25.8 3.6 7.2

104 13.0 26.0 3.6 7.2

105 13.1 26.2 3.6 7.2

106 13.3 26.6 3.6 7.2

107 13.4 26.8 3.6 7.2

108 13.5 27.0 3.6 7.2

109 13.6 27.2 3.6 7.2

110 13.8 27.6 3.6 7.2

 33

CONTRAINDICATIONS OF ABCIXIMAB.

Known hypersensitivity to any component of the product.

Active (internal) bleeding or a history of abnormal bleeding tendencies.
A history of intracranial hemorrhage,neoplasm, AVM or aneurysm.
Thrombocytopenia following prior exposure to abciximab
or other Glycoprotein IIb/IIIa inhibitors .
Coagulopathy, platelet disorder or thrombocytopenia < 100,000.
Stroke within 2 years or any history of hemorrhagic stroke
or stroke with a significant residual neurological deficit.
Major surgical procedure or severe physical trauma within 30 days.
Severe uncontrolled hypertension.
(SBP greater than 180 mm Hg or DBP greater than 110 mm Hg).
Acute pericarditis and significant pericardial effusion.
Clinically significant liver disease.
Concomitant use of other Glycoprotein IIb/IIIa inhibitors.
Administration of warfarin within 7 days unless INR < 1.5.
Pregnancy and breast feeding.
Presumed or documented history of vasculitis.
Suspected or evidence of aortic dissection.
 34

SPECIAL PRECAUTIONS WITH IV GLYCOPROTEIN (GP) IIb/IIIa RECEPTOR

INHIBITORS.

1. PCI with Tirofiban or Abciximab, never use heparin > 7000U, aim 70u/kg
or ACT 200-250s.

2. After PCI, usually no need heparin, however at the operator discretion ,

IV heparin can still be given post PCI together with Tirofiban or Abciximab ,
preferably at low dose not more than 7u/kg/hr.

3. Femoral sheath can be removed while on Tirofiban or Abciximab infusion

post PCI provided - ACT < 150s or APTT < 50s
- 4-6 hour after last dose of heparin.

4.Following femoral sheath removal, pressure should be applied to the

femoral artery for at least 30 minutes.

5. Monitor : FBC after 4 hour of administration and daily during therapy.

6. Stop if : - bleeding occurs .

- Platelet count < 100,000 or decrease more than 50% of baseline.

7. Regarding Tirofiban : - If renal impairment :

- serum creatinine >221mol/l(male)
- serum creatinine >177mol/l(female) ,

reduce the dose of Tirofiban by 50%.

- To avoid if - ESRF
- on dialysis
- serum creatinine > 350mol/l
- creatinine clearance < 30ml/min.
 35

xii) Calcium Channel Blocker .

Indications :

Patient with ongoing angina / ischaemia when

-blocker is ineffective or contraindicated or still
uncontrolled hypertension despite on other drugs.
Not proven in reducing mortality in NSTEACS.

Good LV function. Impaired LV function / Failure

/ AV block/Bradycardia.
Verapamil: 40mg-120mg TDS. Amlodipine: 5mg-10mg OD.
or or
Diltiazem: 30mg-120mg TDS. Felodipine: 5mg-20mg OD.

F Patient NSTEACS, good LV function, no AV block or

bradycardia,if -blocker is contraindicated or ineffective
or inadequate .
Add or use Diltiazem or Use Verapamil.

F Patient NSTEACS with AF / SVT , with good LV function,

if -blocker is contraindicated or ineffective or inadequate.
Add or use Diltiazem or Use Verapamil.

F Patient NSTEACS with concomitant hypertension,

LV systolic dysfunction and heart failure, if ACE-I and or
-blocker are contraindicated or ineffective or inadequate.
Use Amlodipine or Felodipine.

Notes:

Try to avoid combination Verapamil and -blocker

high risk of AV block.

Avoid short acting dihydropyridine Nifedipine in NSTEACS

( as well as in STEMI and chronic stable angina ) without
concomitant -blocker, as it will increase mortality and
further coronary events.

Any LV systolic dysfunction (LVEF 40%) :

-Do Not Use : Verapamil.
Diltiazem.
Nifedipine- short acting.

Any AV block / bradycardia :

-Do Not Use : Verapamil.
Diltiazem.

Not to use if LVEF 30% .

 36

xiii) GENERAL MANAGEMENT.

Bed rest, bed side commode for first 12-24 hours.

Diet - NBM except sips of clear fluids till stable , then soft
salt-free and low fat diet until discharge if stable.

Stool softener - Lactulose 10mls ON.

Sedation - Midazolam 7.5mg ON.

Education / cardiac rehabilitation (CR) : Initiate cardiac

rehabilitation phase 1.
Monitor :
ECG monitor - continuously.
Vital signs regularly : 1hourly till stable than 4hourly.
I/O charting.
BUSE-daily.
12 lead ECG - daily.
6 hourly glucometer if DM or suspect DM.
Relevant investigation and review medications
daily.
FBC - after 4 hour if started on Glycoprotein IIb/IIIa
Inhibitor and daily.
6 hourly APTT if on unfractionated heparin (UFH).

Avoid Valsalva and straining.

Annual influenza vaccination.

Avoid NSAIDs.

Avoid intramuscular injection of any drugs.

Tight control of risk factors : - DM.

- Hypertension.
- Hyperlipidaemia.
- Stop smoking.
 37

5.0 INDICATION FOR CORONARY ANGIOGRAM AND

PERCUTANEOUS CORONARY INTERVENTION (PCI) IN
NSTEACS.

EARLY ( IDEALLY WITHIN 72 HOURS).

F All patients stratified as intermediate and high risk .

URGENT.

F All patients with cardiogenic shock or haemodynamically

unstable.

F All patients WITH THE FOLLOWINGS:

Ischaemic symptoms persist or worsening.

Severe heart failure or pulmonary oedema (Killip III ).
Haemodynamic compromising ventricular arrhythmias
(VT/VF).
Developed mechanical complications ,requiring urgent
surgery e.g severe mitral regurgitation.
Refractory to medical therapy .
Worsening ECG changes despite therapy.
- deepening ST depression 2mm.
- deeper T inversion .

* ALL PCI DONE ONLY AT HUSM,NO INVASIVE LAB AT HRPZ II.

 38

IF INDICATED FOR URGENT PCI : STEPS TO BE TAKEN.

If inpatient HRPZ IIinform cardiologist STAT and arrange for

urgent PCI transfer to HUSM once patient and HUSM
cardiology team agree to take over.

If NOT from HRPZ IIMO/specialist managing the patient must

discuss first with HRPZ II cardiologist for further opinion & plan.
If agreeable by cardiologist HRPZ II,and as well by the patient ,
the involved MO / specialist will liase with HUSM cardiology
team for urgent transfer to HUSM.

As time is crucial, the involved MO/specialist should minimize

the discussions and try to avoid referring to multiple doctors.

Before referring for urgent PCI, ensure:

- Procedure is feasible to be done and agreeable by HUSM
cardiology team .
- Once feasible to be done and agreeable by HUSM cardiology
team , get patient agreement / consent for PCI including
emergency CABG or other related cardiac surgery if indicated.

If patient undecided / refused or procedure not able to be

performed at HUSM, inform cardiologist HRPZ II and arrange
urgent transfer to HRPZ II for further management if agreeable
by patient ( FOR patient not from HRPZ II ).
 39

6.0 INDICATIONS FOR REFERRAL AND REFERRAL CENTRES

FOR STATE OF KELANTAN.

1. Tertiary referral (Hospital):

a. Hospital Raja Perempuan Zainab II (HRPZ II),Kota Bharu.

b. Hospital Universiti Sains Malaysia (HUSM),Kubang Kerian.

2. Indications for referral :

a. Those who are - intermediate-high risk .

- indicated for urgent or early coronary
angiogram /PCI.

b. Those who developed complications secondary to

treatment e.g. bleeding .

c. Those who developed complications related to NSTEACS

- hypotension, persistent chest pain,arrhythmias, heart
block, pericarditis, acute pulmonary oedema ,cardiogenic
shock or other complications.

d. Those who are unable to receive adequate treatment /

monitoring / unstable to be managed at local centre /
hospital or after clinical assessment / discussion with
cardiologist, specialist or senior MO (Medical dept) at any
referral centre and deemed need to be transferred for
better care.

3. Facilities / instrument needed before transferring patients :

a. Ambulance with well equipped resuscitation instrument

and trained staff / paramedic and doctor.
b. Cardiac monitoring.
c. Defibrillator.
d. Oxygen.
e. Resuscitation set.
f. Suction machine.

4. Stabilise patient before transfer and discuss with

tertiary centre specialist or doctor before transferring patient.

5. Attach - referral letter.

- all ECGs and CXR.
- document / copies of all investigations and
treatment given.
LOW RISK. 7.0 NSTEACS FLOWINTERMEDIATE
CHART. AND
Rx: IV RISK
Nitrate. STRATIFICATION
Antiplatelets.
HIGH AND
Anticoagulant.
RISK.
Medical Rx.
URGENT CORONARY ANGIOGRAM ( UA / NSTEMI. ) EARLY CORONARY
CONTINOUS CLINICAL ASSESSMENT.
ANDInvasive
Non PCI IF AT ANY TIME WITH :
Stratification. Medical Rx .
ANGIOGRAM AND 40
- EST. blocker. ACE-I/ARB. Statin.
PCI WITHIN 72 HRS.

Elective
Cardiogenic
Coronary

shock or
Angiogram
haemodynamically unstable. Spironolactone.
Calcium blocker.
Ischaemic symptoms persist.
Severe heart failure or pulmonary
oedema (Killip III ).
Haemodynamic compromising
ventricular arrhythmias.
Developed mechanical
complications ,requiring urgent
surgery e.g severe mitral
regurgitation.
Refractory to medical therapy.
Worsening ECG changes despite
therapy.
- deepening ST depression 2mm.
- deeper T inversion.

1. CCU
-HRPZ II - 097452193
- 097452185
-HUSM- 097664847
 41

8.0. IMPORTANT CONTACT NUMBERS.

1. CCU HRPZ II - 097452185 / 097452193

2. CCU HUSM - 097673768 / 097673769

3. FAX CCU HRPZ II - 097479532

4. CRW HRPZ II - 097452192 / 097452195

5. CASUALTY HRPZ II - 097452092 / 097452103

6. CASUALTY HUSM - 097673223 / 097673231

7. INVASIVE LAB HUSM - 097673986 / 097673987

8. OPERATOR HRPZ II - 097452000

9. OPERATOR HUSM - 097673000

PLEASE CONTACT OPERATOR FOR RELEVANT

CARDIOLOGIST OR PHYSICIAN.
 42

Appendix 1.

Diagnostic and preanticoagulant checklist :

1) Blood pressure : 2) Estimate body weight(kg) :

Right arm :
Left arm :

3) Time interval symptoms and presentation to hospital.

a. Pain began:am / pm.

b. Arrival time:am / pm(to hospital).

4) Diagnosis of NSTEACS (pls tick) :

NSTEMI Unstable angina

NSTEACS ( tick if await cardiac markers or not available )

If cardiac markers elevated = NSTEMI.

If cardiac markers not elevated = Unstable angina.
If cardiac markers not available / pending : term NSTEACS is
used until it is available,once available tick NSTEMI or Unstable
angina.

Yes No Not applicable or

available
Typical Chest Pain

ECG Changes

Elevated Cardiac
Enzymes / Markers
 43

5) Absolute Contraindication of Anticoagulant. (Pls tick.)

Yes No

1.Any prior intracranial haemorrhage.

2.Known structural cerebral vascular lesion.

(e.g.AVM or Aneurysm.)

3.Known malignant intracranial neoplasm.

(primary or metastatic.)

4.Already significantly prolonged INR or

APTT.

5.Suspected or evidence of aortic

dissection.

6.Active bleeding or bleeding diathesis.

(excluding menses.)

7.Hypersensitivity to anticoagulant.

8.Bacterial endocarditis.
 44

6) Relative Contraindication of Anticoagulant. (Pls tick.)

Yes No

1.Untreated bleeding disorders such as Haemophilia

or other haemorrhagic disorders.

2.Severe uncontrolled hypertension on presentation.

(SBP greater than 180 mm Hg or DBP greater than
110 mmHg.)

3.Thrombocytopenia with platelets < 60,000.

4.History of heparin-induced thrombocytopenia.

5.Major surgery (within less than 3 weeks).

6.Recent (within 2 to 4 weeks) internal bleeding.

7.Noncompressible vascular punctures.

8.Other intracranial pathology not covered in absolute

Contraindication.

9.Significant pericardial effusion - undrained or without

regular ultrasonographic monitoring.

10.Active peptic ulcer.

11.Liver failure or advanced liver disease.

12.Underlying malignancy.

13.Unconscious, confused, agitated.

14.Severe renal dysfunction.

(Creatinine clearance < 30ml/min)
-for LMWH and Fondaparinux.
 45

Appendix 2.

- Checklist for the management of NSTEACS on presentation /

admission.
- Pls tick appropriately.

TREATMENT / ACTION YES NO

1. Risk stratification

2. IV Heparin infusion / Enoxaparin / Fondaparinux

3. Oxygen

4. Nitrate
a. Sublingual GTN 0.5mg
b. IV Isoket / GTN

5. Aspirin
a. Bolus
b. Maintenance

6. Clopidogrel
a. Bolus
b. Maintenance

7. Beta-Blocker

8. ACE Inhibitor / ARB

9. Aldosterone antagonist

10. Pain Medication + antiemetic

IV Morphine sulfate 2 to 4mg at 5-15minute intervals as needed
to control pain.
IV Metoclopramide 10mg or IV Promethazine 25mg

11. Statin

12. Insulin for hyperglycaemia

13. Stool Softener

14. Sedative / Anxiolytic

15.
Others __________________________________________

If Yes : please state type,dosage and time given.

If No: please state the reasons
 46

ACKNOWLEDGEMENTS.

We would like to express our enduring gratitude and appreciation to the following
individuals and group for their invaluable,unfailing assistance and support :

Director General of Health Malaysia.

Deputy Director General (Medical) of Health Malaysia.
Director of Medical Development, Ministry of Health Malaysia.
Head of Cardiology Service, Ministry of Health Malaysia.
Health Director of Kelantan.
Deputy Health Director (Medical) of Kelantan.
Director Hospital Raja Perempuan Zainab II,Kota Bharu,Kelantan
Head of Medicine, Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan .
Head of Accident & Emergency /Specialists, Hospital Raja Perempuan Zainab II,
Kota Bharu, Kelantan.
Consultants/Specialists, Department Medicine Hospital Raja Perempuan Zainab
II,Kota Bharu, Kelantan.
Consultant/Specialist,Department Medicine,Hospital K.Krai, Kelantan.
Specialist, Department Medicine, Hospital Tanah Merah , Kelantan .
Medical officers, Department Medicine Hospital Raja Perempuan Zainab II, Kota
Bharu, Kelantan.
Matrons,sisters,assistant medical officers ,staff nurses and other supportive staff,
Department Medicine Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan.
 47

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 48

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