GUIDELINES FOR MANAGEMENT OF NON ST ELEVATION ACUTE CORONARY SYNDROME (NSTEACS) FOR MINISTRY OF HEALTH ( MOH ) HOSPITALS & HEALTH CENTRES IN KELANTAN.
SECOND EDITION 2012.
2
PREPARED BY :
1.DR HAJI AZERIN OTHMAN. BMBS (Flin. Sth. Aust.). MRCP 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.
2
PREPARED BY :
1.DR HAJI AZERIN OTHMAN. BMBS (Flin. Sth. Aust.). MRCP 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.
3
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 / admission and risk stratification.
8
4.3 Management of NSTEACS: Pharmacotherapy.
15
5.0
INDICATIONS FOR CORONARY ANGIOGRAM AND PERCUTANEOUS CORONARY INTERVENTION (PCI) IN NSTEACS.
37
6.0
INDICATIONS FOR REFERRAL AND REFERRAL CENTRES FOR STATE STATE OF KELANTAN.
39
7.0
NSTEACS FLOW CHART.
40
8.0
IMPORTANT CONTACT NUMBERS.
41
APPENDICES. Appendix 1: Diagnostic and and preanticoagulant checklist.
42
Appendix 2: Checklist for the management management of NSTEACS on presentation / admission.
45
ACKNOWLEDGEMENTS.
46
REFERENCES
47
4
1.0 INTRODUCTION AND BACKGROUND. Cardiovascular disease is the commonest cause of mortality in government hospitals. Coronary artery disease (CAD) is t he 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 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 normal in Unstable Angina.Until biochemical 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 over days , weeks and with repeated episodes or admissions until optimal pharmacotherapy and revascularization procedures are instituted 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 patients presenting 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 guidelines are an updated updated version version with new changes compared to the first edition which was circulated in 2009.
5
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.
6
3.0 TRIAGE. EMERGENCY DEPARTMENT OF HOSPITALS. • HEALTH CARE CENTRES / CLINICS. •
ACUTE CHEST PAIN OR EQUIVALENT SYMPTOMS.
PRIMARY TRIAGE BY PARAMEDIC
TYPICAL OR SUSPECT OF ACS.
ATYPICAL OR SUSPECT OF NON ACS.
SECONDARY TRIAGE BY PARAMEDIC
ABNORMAL / SUSPICIOUS
ECG NORMAL
•RED
ZONE / TREATMENT ROOM. •URGENT ECG & BLOOD INVESTIGATIONS. •URGENT REVIEW & TREATMENT BY MO. •TRANSFER IF INDICATED. (WITHIN 30MIN OF PRESENTATION).
ACS - Acute Coronary Syndrome.
•YELLOW
/ GREEN ZONE / CLINIC. •RELEVANT INVESTIGATIONS. •REASSESS BY MO. •TRANSFER IF INDICATED.
7
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.
8
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.
9
TABLE 1.TYPES OF RISK SCORES USED IN CLINICAL PRACTICE
10
TABLE 2.TIMI RISK SCORE. 1. AGE 2.
65.
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.
• LOW.
SCORE.
ALL CAUSE MORTALITY , NEW & RECURRENT MI.
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
12
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%.
13
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%.
14
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.
16
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 : " IV ISOKET OR GTN : 10µg/min - 200µg/min. ( 0.6mg/hr -12mg/hr ).
•
Dosage oral or other nitrates : " S/L GTN : 0.5mg PRN. " ORAL ISOSORBIDE DINITRATE (ISORDIL) : 10mg - 30mg TDS. " NITRODERM TRANSDERMAL PATCH : 5mg for 8 - 12hr /day * * Need 8-12hr free period to avoid tolerance.
17
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.
18
If 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 # 265µmol/l. - If creatinine > 265µmol/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 # 221µmol/l(male) or # 177µmol/l(female) . - If creatinine > 221µmol/l(male) or >177µmol/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).
!
20
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.
21
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) ii) iii) iv) v) vi) vii)
•
Airways disease - COAD/ Bronchial asthma. Moderate to severe heart failure. Hypotension SBP < 100 mmHg or " 30 mmHg drop from baseline BP Bradycardia < 60 bpm. PR interval > 240 ms. Secondary or third degree AV block. Severe peripheral vascular disease (PVD).
Dosage : "If LV function good (LVEF > 40%) , use
Atenolol : 25mg -100mg OD. or Metoprolo l: 25mg -100mg BD. "If 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 > 221µmol / 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 > 221µmol / 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 > 221µmol/l(male). Creatinine > 177µmol/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 t he 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). 0.15µg/kg/min.
25µg/kg. 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 > 350µmol/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 >221%mol/l(male) - serum creatinine >177%mol/l(female) , & reduce the dose of Tirofiban by 50%.
- To avoid if - ESRF - on dialysis - serum creatinine > 350%mol/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. or Diltiazem: 30mg-120mg TDS.
Amlodipine: 5mg-10mg OD. or Felodipine: 5mg-20mg OD.
" 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. " Patient NSTEACS with AF / SVT , with good LV function, if $-blocker is contraindicated or ineffective or inadequate. & Add or use Diltiazem or Use Verapamil. " 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 & high risk of AV block.
-blocker
% 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). " All patients stratified as intermediate and high risk .
URGENT. " All patients with cardiogenic shock or haemodynamically unstable. " 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 II!inform cardiologist STAT and arrange for urgent PCI transfer to HUSM once patient and HUSM cardiology team agree to take over.
• If
NOT from HRPZ II!MO/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. INTERMEDIATE AND 7.0 NSTEACS FLOW CHART. RISK STRATIFICATION AND Rx: • IV Nitrate. • Antiplatelets.HIGH • Anticoagulant. RISK. CORONARY • Medical Rx. URGENT CORONARY ANGIOGRAM ( UA / NSTEMI. ) EARLY CONTINOUS CLINICAL ASSESSMENT. • Medical Rx . ANDInvasive PCI IF AT ANY TIME WITH : ANGIOGRAM AND • Non Stratification. • $ blocker. • ACE-I/ARB. • Statin. PCI WITHIN 72 HRS. - EST. • Cardiogenic shock or Coronary Angiogram • Elective • Calcium blocker. haemodynamically unstable. • Spironolactone. • 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
40
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 Typical Chest Pain ECG Changes Elevated Cardiac Enzymes / Markers
No
Not applicable or available
43
5) Absolute Contraindication of Anticoagulant. (Pls tick.) Yes
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.
No
44
6) Relative Contraindication of Anticoagulant. (Pls tick.) Yes
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.
No
45
Appendix 2. - Checklist for the management of NSTEACS on presentation / admission. - Pls tick appropriately. TREATMENT / ACTION
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
YES
NO
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
REFERENCES 1. The National Heart Foundation of Australia, Cardiac Society of Australia and New Zealand .Guidelines for the management of acute coronary syndromes . Med.J Aust 2006;184 (8 Suppl): S1-S32. 2. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, et al.ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction). Circulation. 2007;116:803- 877. 3. Bassand JP, Hamm CW, Ardissino D, et al . Guidelines for the diagnosis and treatment of non -ST-segment elevation acute coronary syndromes.The Task Force for the for the diagnosis and treatment of non -ST-segment elevation acute coronary syndromes of the European Society of Cardiology (ESC). Eur Hear t J 2007;28:1598- 1660
4. R. Scott Wright, Jeffrey L. Anderson, Cynthia D. Adams, Charles R. Bridges, Donald E. Casey, Jr, Steven M. Ettinger, Francis M. Fesmire, Theodore G. Ganiats Hani Jneid, A. Michael Lincoff, Eric D. Peterson, George J. Philippides, Pierre Theroux, Nanette K. Wenger, and James Patrick Zidar .2011 ACCF/AHA Focused Update of the Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction (Updating the 2007 Guideline): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J. Am. Coll. Cardiol. 2011;57;1920-1959 5. Canadian Cardiovascular Society Antiplatelet Guideline 2010 - Recommendations http://www.ccs.ca/consensus_conferences/cc_library_e.aspx
6. Zeljko Reiner , Alberico L. Catapano , Guy De Backer , et al .ESC/EAS Guidelines for the management of dyslipidaemias.The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011 ; 32 :1769-1818 .
