Transcript ACUTE CORONARY SYNDROMES

ACUTE CORONARY
SYNDROMES
R MAHARAJ
EMERGENCY MEDICINE
LECTURE OUTLINE
• INTRODUCTION –
EPIDEMIOLOGY/PREVALENCE/DEFINITION
• PATHOPHYSIOLOGY OF ACUTE CORONARY
SYNDROMES
• APPROACH TO SUSPECTED ACUTE
CORONARY SYNDROME – GUIDELINE
UPDATE
• TREATMENT/MANAGEMENT UPDATE
INTRODUCTION
• Coronary Artery Disease – leading cause of morbidity & mortality in
industrialised nations.
• Although decrease in cardiovascular mortality  still major cause of
morbidity & burden of disease.
• South African perspective of cardiovascular disease:
• “A World in One Country” - Yusuf et al
• Epidemiological transitions of cardiovascular disease.
• HIGH RISK POPULATION FOR CAD/ACS:
INDIAN/WHITE/COLOURED
• INCREASING rate in Black population – lifestyle/socioeconomic
changes, urbanisation
• GF Jooste stats: 23.8% of admissions to resus. unit for chest
pain/acs related (stats 1Jan 2009 – 28 Feb 2009) 150/628 entries.
• In US – 2004 – 1.56 million admissions for ACS – 669 000 for
unstable angina, 896 000 for MI
• Higher prevelance for NSTEMI.
DEFINITIONS
• CAD is a continuum of disease….
• Angina -> unstable angina -> AMI -> sudden cardiac death
• Acute coronary syndrome encompasses unstable angina, NSTEMI,
STEMI
• Stable angina – transient episodic chest pain d/t myocardial
ischaemia, reproducible, frequency constant over time.usually
relieved with rest/NTG.
• Classification of angina – Canadian Cardiovascular Society
classification.
Canadian Cardiovascular Association Classification of
Angina
CLASS 1
NO PAIN WITH ORDINARY PHYSICAL ACTIVITY
CLASS 2
SLIGHT LIMITATION OF PHYSICAL ACTIVITY –
PAIN OCCURS WITH WALKING, CLIMBING
STAIRS,STRESS
CLASS 3
SEVERE LIMITATION OF DAILY ACTIVITY – PAIN
OCCURS ON MINIMAL EXERTION
CLASS 4
UNABLE TO CONDUCT ANY ACTIVITY WITHOUT
PAIN, PAIN AT REST
• UNSTABLE ANGINA –
• Pain occurring at rest – duration > 20min, within one week of first
visit
• New onset angina – ~ Class 2 severity, onset with last 2 months
• Worsening of chest pain – increase by at least 1 class, increases in
frequency, duration
• Angina becoming resistance to drugs that previously gave good
control.
• NB! ECG – normal, ST depression(>0.5mm), T wave changes
• ACUTE MYOCARDIAL INFARCTION –
• ECC/ACC DEFN –rise and fall in cardiac enzymes with one or more
of the following:
• Ischaemic type chest pain/symptoms
• ECG changes – ST changes, pathological Q waves
• Coronary artery intervention data
• Pathological findings of an acute MI
• NSTEMI = UNSTABLE ANGINA SYMPTOMS/FINDINGS +
POSITIVE CARDIAC ENZYMES
• STEMI = ST ELEVATION ON ECG + SYMPTOMS
• WHY IS IT IMPORTANT TO RECOGNISE PATIENTS WITH
UNSTABLE ANGINA??
• 5 -17% suffer an MI within a week after admission.
• 3 -15% die within a year.
ACS PATHOPHYSIOLOGY
• Distruption of coronary artery
plaque -> platelet
activation/aggregation
/activation of coagulation
cascade -> endothelial
vasoconstriction ->intraluminal
thrombus/embolisation ->
obstruction -> ACS
• Severity of coronary vessel
obstruction & extent of
myocardium involved
determines characteristics of
clinical presentation
APPROACH
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Identifying those with chest pain suggestive of IHD/ACS.
Thorough history required:
Character of pain
Onset and duration
Location and radiation
Aggravating and relieving factors
Autonomic symptoms
• TYPICAL VS ATYPICAL HISTORY
• Failure to recognise symptoms other than chest pain -> approx 2 hr
delay in seeking medical attention
CHARACTERISTICS OF TYPICAL ANGINAL CHEST PAIN (ADAPTED
FROM ROSEN’S, EMERGENCY MEDICINE)
CHARACTERISTIC
SUGGESTIVE OF ANGINA
LESS SUGGESTIVE OF
ANGINA
TYPE OF PAIN
DULL
PRESSURE/CRUSHING
PAIN
SHARP/STABBING
DURATION
2-5 MIN, <20 MIN
SECONDSTO
HOURS/CONTINUOUS
ONSET
GRADUAL
RAPID
LOCATION/CHEST WALL
TENDERNESS
SUBSTERNAL, NOT
TENDER TO PALP.
LATERAL CHEST
WALL/TENDER TO PALP.
REPRODUCIBALITY
WITH
EXERTION/ACTIVITY
WITH
BREATHING/MOVING
AUTONOMIC SYMPTOMS
PRESENT USUALLY
ABSENT
ATYPICAL PAIN
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RISK FACTORS FOR DEVELOPING ATYPICAL PAIN:
Diabetes, females, non white patients, elderly, dementia, no prior history of
MI
ATYPICAL SYMPTOMS:
GIT symptoms
Syncope
SOB
Pleuritic/positional pain
Chest wall tenderness
No chest pain/symptoms
NRMI 2 STUDY – MI without chest pain -> increased risk of death (23% vs
9%)
More complications – hypotension,heart failure, stroke
Delayed ED presentation, delayed intervention
RISK STRATIFICATION IN ACS
• Reasons :
• Provides prognostic information
• Determines treatment and level of intervention -> low risk patients –
early discharge, high risk -> admission to high care
• Helps decongest the ED and make available medical resources to
more needy patients
• Risk stratification should be ongoing – at admission, 6-8 hrs, 24hrs,
discharge
TOOLS USED IN RISK STRATIFICATION
• HISTORY
• ECG
• BIOCHEMICAL MARKERS
ECG
• First point of entry into ACS algorithm
• Abnormal or normal
• Neither 100% sensitive or 100% specific for AMI
• Single ECG for AMI – sensitivity of 60%, specificity 90%
• Represents single point in time –needs to be read in context
• Normal ECG does not exclude ACS – 1-6% proven to have AMI, 4%
unstable angina
• GUIDELINES:
• Initial 12 lead ECG – goal door to ECG time 10min, read by
experienced doctor (Class 1 B)
• If ECG not diagnostic/high suspicion of ACS – serial ECGs initially
15 -30 min intervals (Class 1 B)
• ECG adjuncts – leads V7 –V9, RV 4 (Class 2a B)
• Continuous 12 lead ECG monitoring reasonable alternative to serial
ECGs (Class 2a B)
BIOCHEMICAL MARKERS
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IDEAL MARKER:
High concentration in myocardium
Myocardium specific
Released early in injury
Proportionate to injury
Non expensive testing
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Troponins
CKMB
Myoglobin
Other markers
TROPONINS T/I
• Troponin T vs I –
• both equivalent in diagnostic and prognostic abilities ( except in
renal failure – Trop T less sensitive)
• Elevation ~ 2hrs to 12hrs
• ~30 – 40% of ACS patients without ST elevation – had normal
CKMB but elevated troponins on presentation
• Meta-analysis (Heindereich et al) – odds of death increased 3 to 8
fold with positive troponin
• Mortality at 42 days in troponin positive patients
MYOGLOBIN
• Rapid release within 2 hours
• Not cardiac specific
• Rule out for NSTEMI rather than rule in.
CKMB
Used in conjunction with troponins
Useful in diagnosing re-infarction
MARKER CHANGE SCORES
• 2 hour delta CKMB mass
• Aim – to exclude MI within 6hrs of symptom onset
• Determine changes in serum marker levels over certain time
intervals –delta values
• Increasing values while still within normal range suggestive of
ischaemia – more rapid anti- ischaemic mxn.
OTHER MARKERS
• INDICATORS OF INFLAMMATION OR ACTIVATION OF
COAGULATION CASCADE:
• Myeloperoxidase, soluble CD40 ligand, IL6, hsCRP, d dimer,
prothrombin fragment 1 & 2
• Elevated before onset of irreversible injury
• Lack specificity
• Complex lab assays
ISCHAEMIA MODIFIED ALBUMIN
• Measured with albumin cobalt binding assay
• In ischaemia -> decreased binding of albumin to cobalt
• Increased with minutes of ischaemia – elevated for 6-12hrs – gone
by 24hrs
• ~90% negative predictive value
• Combined with myoglobin/CKMB/troponin – increases diagnostic
sensitivity of ischaemia by 40%
• Possible role for rule criteria in low risk patients
• Positive IMA – high risk patients – more aggressive mxn
• Positive in hypoxic disorders – poor specificity in this setting
• B –type Natriuretic Peptide:
• released from heart muscle in response to increased ventricular wall
stress.
• Studies – BNP not a specific marker but a strong predictor of ACS
especially in patients with chest pain, no ECG changes, non
diagnostic troponins.
• Also positive in heart failure, PE, atrial arrythmias, renal failure
• Pregnancy Associated Plasma Protein A (PAPP-A):
• Released when plaque ruptures
• Predictor of ischaemia
• HEART FATTY ACID BINDING PROTEIN (HF ABP)
• Identifies AMI <4hrs after onset
• Protein involved in myocardial lipid synthesis, but also expressed
outside heart
• Therefore may be sensitive but not specific for injury
• Possible role in multi-marker strategy
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IMAGING MODALITIES
Cardiac MRI
Multidetector CT for coronary calcification
Coronary CT angiography
Undergoing clinical evaluation
• 2007 ACC/AHA guidelines:
• Cardiac biomarkers measured in all patients with suspicion of ACS
(Class 1 B)
• Troponin preferred marker( Class 1 B)
• If troponin negative within 6 hours of onset, repeat 8-12hours
later(Class 1 B)
• Remeasuring of positive biomarkers to determine infarct
size/necrosis (Class 2a B)
• Patients presenting within 6 hours of symptom onset – myoglobin in
conjunction with troponin measured (Class 2b B)
• 2hr delta CKMB/Delta troponin considered in <6hr presentation
(Class 2b B)
• BNP level – for global risk assessment(Class 2b B)
• Class 3 – AST/LDH/CK without CKMB
RISK STRATIFICATION MODELS
TIMI RISK SCORE –increase in mortality with increasing score ~40%
all cause mortality at 14 days for patients requiring urgent
revascularisation
WHICH MODEL IS MOST APPROPRIATE??
• 2007 ACS/AHA GUIDELINES:
• Risk stratification models useful in decision making with regard to
treatment options ( Class 2a B)
• TIMI vs GRACE vs PURSUIT
• PURSUIT & GRACE risk scores allow better discrimination of in
hospital and 1 year mortality in patients compared to TIMI. (Andrew
et al, Risk scores for risk stratification in ACS …)
• What’s appropriate in our setting???
MANAGEMENT ALGORITHM
MANAGEMENT UPDATE
2007ACS/AHA GUIDELINES:
Rapid catergorisation of patient (Class 1 C)
Possible ACS, non diagnostic ECG/biomarkers – observed in facility
with cardiac monitoring (Class 1 C)
Alternative to in patient treatment: for those with 12hr ECG/markers
negative – stress ECG in 72hrs (Class 1 C)
Giving precautionary treatment for those for OPD stress (Class 1 B)
INITIAL INVASIVE
VS
INITIAL CONSERVATIVE STRATEGY
• CLASS 1 RECOMMENDATIONS:
• Early invasive strategy for refractory angina, hemodynamic
instability (LOE B)
• Early invasive strategy for stabilised patients with elevated risk for
clinical events.
• High risk factors include:
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Recurrent angina, ischaemia at rest or minimal activity
Elevated troponins
New ST depression
Signs of heart failure/worsening mitral regurg.
Ventricular tachycardia
Prior CABG
PCI in last 6 months
High TIMI/GRACE scores
LVEF < 40%
• CLASS 2b
• May opt for initial conservative strategy in stabilised high risk
patients – dependent on patient/physician preference (LOE B)
• CLASS 3
• Invasive strategy -not recommended in patients with multiple co
morbidities, low risk patients, patients not consenting.(LOE C)
UA/NSTEMI –PHARMACOTHERAPY UPDATE
• GENERAL:
• IV B Blockers downgraded from Class 1 to 2a recommendation.
(COMMIT Trial)
• Oral B Blockers in first 24hrs still Class 1 – but not used in signs of
heart failure, cardiogenic shock and reactive airway disease.(LOE B)
• MORPHINE downgraded from Class 1 to 2a – findings from
CRUSADE Registry
NSTEMI- PHARMACOTHERAPY UPDATE
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ANTIPLATELET THERAPY:
CLASS 1 RECOMMENDATION
Aspirin to all patients as soon as possible and continued (if no C/I) (LOE A)
Initial dose 162 -325mg
Maintenance 75 -162mg
No added benefit from higher doses except post stenting
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Clopidogrel for those allergic to aspirin or major GI bleeding (LOE A)
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For initial invasive strategy – aspirin + clopidogrel or IV glycoprotein 2b/3a
therapy (LOE A)
Abciximab if no delay in angiography/PCI, eptifibatide/tirofiban if delayed
angiography(LOE B)
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• CLASS 2a
• In patients managed conservatively who develop recurrent
ischaemia – on clopidogrel/ASA/Anticoagulant – can add
glycoprotein inhibitor. (LOE C)
• Invasive strategy – can use clopidogrel + glycoprotein
inhibitors(LOE C)
• CLASS 2b
• In patients managed conservatively – can add glycoprotein inhibitor
therapy, in addition to aspirin & anticoagulant (LOE B)
CLASS 3
• ABCIXIMAB should not be given if PCI not planned (LOE A)
• For initial conservative strategy:
• Aspirin + Clopidogrel + anticoagulant – administered for 1
month(LOE A), continued ideally up to 1 year(LOE B)
• If initial conservative strategy selected but patient has recurrent
ischaemic symptoms/heart failure/arrythmias – diagnostic
angiography recommended. Clopidogrel or Glycoprotein 2b/3a
inhibitors should be added before angiography.
ANTICOAGULANT THERAPY
CLASS 1
• Anticoagulant therapy should be added as soon as possible
• For patients undergoing angiography/PCI – enoxaparin/UFH (LOE
A) of Bivalirudin/ fondaparinux (LOE B)
• For conservative strategy: enaxaparin, UFH (LOE A), fondaparinux
• For patients with increased risk of bleeding with conservative
strategy – fondaparinux
• CLASS 2a
• Enoxaparin /fondaparinux vs UFH
• Enoxaparin/fondaparinux preferred except in those undergoing
CABG within 24hrs (LOE B)
ADDITIONAL MANAGEMENT
• STRESS TEST should be performed for those managed
conservatively.
• If stress test positive/ high risk – needs diagnostic
angiography(Class 1 LOE A)
• If classed as low risk –
• need to continue aspirin indefinitely ( LOE A)
• Clopidogrel for at least 1 month(LOE A), ideally up to 1 year(LOE B)
UA/NSTEMI ALGORITHM- INVASIVE STRATEGY
UA/NSTEMI ALGORITHM –CONSERVATIVE STRATEGY
STEMI
• PHARMACOLOGICAL UPDATE:
• ANALGESIA – changes from 2004 guidelines
• MORPHINE: still remains Class 1 C for STEMI, titrated doses
• NSAIDS/COX 2 INHIBITORS: those on it should have it
discontinued ( increased risk of mortality, re infarction, heart failure,
myocardial rupture) Class 1 C
• NSAIDS should not be administered in hospital for MI (Class 3)
• BETA BLOCKERS
• Modified recommendation
• Oral Beta Blockers should be initiated in first24rs, if no contraindications (heart failure, risk of cardiogenic shock) Class 1 B
• Patients with early contraindications -> re- evaluated later for
possible use
• Role of IV B blockers – used in hypertensive patients with STEMI
Class 2a B
• Class 3 LOE A – IV B blockers should not be administrated to
patients with heart failure, risk of cardiogenic shock
• No major changes to reperfusion strategies.
• Emphasis on decreasing ischaemic time.
• Increase use of prehospital 12 lead ECG emphasised.
• In PCI capable hospital – door to PCI time 90 min (Class 1 A)
• In non PCI capable hospital – door to needle time 30 min or timeous
transfer to PCI capable hospital. (Class 1 B)
REPERFUSION STRATEGY
FIBRINOLYTICS
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AVAILABLE FIBRINOLYTICS:
STREPTOKINASE – 1.5mu infusion over 30min (1hour –ACLS)
rtPA – accelerated infusion over 1.5hrs
- 15mg IV bolus, 0.75mg/kg over 30 min, 0.5mg/kg over 1hr
ANISTREPLASE – 30 U IV over 5 min
TENECTEPLASE – 30 TO 50 MG
RETEPLASE – 10 U IV bolus, ffd. 10U IV after 30 min
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WHICH FIBRINOLYTIC TO USE???
GISSI 2 trial – tPA vs Streptokinase , no difference in mortality, marginally
higher stroke rate with tPA (1.3% vs 1%)
GUSTO 1 trial – early vessel patency post infract assoc. with better survival.
Accl. tPA/heparin cf comb. Streptokinase/tPA/heprain cf strep with IV vs
S/C heparin
Outcome – better flow rates with accl. tPA -> lower mortality rates
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• ASSENT 2 TRIAL – tenecteplase vs aTPA
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- tenecteplase was equally or minimally more
effective, especially in those presenting > 4hrs after symptom onset.
• Fibrinolysis combined with glycoprotein 2b/3a inhibitors – no overall
advantage (ASSENT 3, GUSTO 5 trials)
• RESCUE PCI:
• CLASS 1 LOE B – angiography with +/- PCI in patients (<75 yrs)with
cardiogenic shock, severe heart failure, ventricular dysrythmias
• Class 2a – persistent ischaemic symptoms post fibrinolysis,
haemodynamic instability, electrical instability (LOE C)
• New recommendation – PCI for failed fibrinolytic therapy (less than
50% decrease in ST elevation in worst lead, 90min post fibrinolytic
therapy, or large area of myocardium injured) LOE B
• Class 3 – angiography performed if invasive strategy
contraindicated, or patient refusal (LOE C)
ANTICOAGULANT ADJUNCTS
• NEW RECOMMENDATIONS:
CLASS 1
• Patients undergoing fibrinolysis should be kept on anticoagulants for
atleast 48 hrs and preferably the duration of hospital stay. LOE A
• Anti coagulants with proven efficacy:
• Unfractionated Heparin - keeping aPTT 1.5 – 2 sec above control
(LOE C)
• Enoxaparin (Clexane) – initial dosage of 30mg IV bolus – ffd by
1mg/kg 12hrly, caution in renal impairment (LOE A)
• Fondaparinux – 2.5mg IV, ffd by 2.5mg dly S/C maintenance for
duration of hospitalisation (LOE B)
ANTICOAGULANTS
• CLASS 2a recommendation to use anticoagulants in STEMI without
reperfusion.
• UFH (LOE B)
• LMWH (LOE C)
• Fondaparinux (LOE B)
THIENOPYRIDINES
CLASS I
• CLOPIDOGREL – now recommended in all STEMI patients in
addition to aspirin, whether undergoing reperfusion or not. Dosage
75mg daily(LOE A)
• Duration -14 days (LOE B)
CLASS 2 A
In patients < 75yrs – Clopidogrel 300mg loading dose
recommended(LOE C)
Long term maintenance therapy should be considered, 75mg dly for 1
year (LOE C)
SECONDARY PREVENTION
• INCREASED FOCUS ON SECONDARY PREVENTION:
• SMOKING CESSATION
• DIET MODIFICATION/WT CONTROL
• BP CONTROL
• LIPID MANAGEMENT
• EXERCISE
• DIABETES MANAGEMENT
• Despite good reperfusion strategies approx. 1/3 of patients
worldwide miss out.
• Attributed to – delayed presentation, atypical presentation,
complicated disease presentation, older age
• SYMPTOMS OF INFARCT BUT NO ESTABILISHED ECG
CHANGES - keep in mind aortic dissection, GIT disease, other
chest pathology
CONCLUSION
• With increase burden of CVD, and lack of health resources risk
stratification becomes important.
• Emphasis should also be placed on primary &secondary prevention
of ACS.
• Early intervention helps prevent complications, decreases morbidity
& mortality
• The way forward – fully equipped CHEST PAIN OBSERVATION
UNIT
REFERENCES
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EDITORS MARX ET AL, ROSEN’S EMERGENCY MEDICINE: CONCEPTS AND CLINICAL
PRACTICE, 6TH EDITION
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PAUL PD ET AL, KEY ARTICLES IN MANAGEMENT OF ACS & PCI -2007 UPDATE,
PHARMACOTHERAPY 2007:27(12), 1722 -1750
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WHITE HD, DEFINING THE LIMITS OF ACS, CARDIOLOGY AT THE LIMITS IV, EDITORS:
OPIE LH, YELLON DM
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YUSUF S, THE GLOBAL EPIDEMIC OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE,
CARDIOLOGY AT THE LIMITS IV, EDITORS: OPIE LH, YELLON DM
•
FOX KA, MANAGEMENT OF ACS: AN UPDATE, HEART.2004 JUNE, 90(6):698 -706
•
ANDERSON ET AL, ACC/AHA 2007 GUIDELINES FOR MXN OF U/A,NSTEMI – EXECUTIVE
SUMMARY – DOWNLOADED content.onlinejacc.org
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SIX AJ ET AL, CHEST PAIN IN THE ER: VALUE OF THE HEART SCORE, NETH. HEART J.
2008 JUNE,16(6):191 -196
•
ANTMAN EM ET AL, 2007 FOCUSSED UPDATE OF ACC/AHA 2004 GUIDELINES FOR MAXN
OF PATIENTS WITH STEMI, DOWNLOADED http://circ.ahajournals.org
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McCANN CJ ET AL, NOVEL BIOMARKERS IN EARLY DIAGNOSIS OF AMI COMPARED WITH
CARDIAC TROPONIN T, EUROPEAN HEART JOURNAL 2008,29(23): 2843 -2850
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KING III SB ET AL, 2007 FOCUSSED UPDATE OF ACC…..FOR PCI, JOURNAL OF AMERICAN
COLLEGE OF CARDIOLOGY, VOL 51, NO 2, 2008