Transcript Slide 1

ACS and Thrombosis in the
Emergency Setting
NSTEMI
ACS Diagnosis Flow Chart
ADMISSION
CHEST PAIN
WORKING DIAGNOSIS
ACUTE CORONARY SYNDORME
ECG
persistent
ST-elevation
BIO-CHEMISTRY
DIAGNOSIS
STEMI
ST/Tabnormalities
normal or
undetermined
ECG
troponin
rise/fall
troponin
normal
NSTEMI
Unstable
Angina
European Heart Journal 2011; 32, 2999-3054 (ESC Guidelines for Management of ACS in patients without ST elevation)
Q1: Do you routinely use and rely on an
ischemic pain assessment protocol?
a)Yes
b) No
Chest Pain 9% of all ER Visits (1)
→ 25-40% admitted
→ 13-23% have Acute Coronary Syndrome(1)
→ < 5% have STEMI (2)
→ < 25% Non STE ACS (3)
→ 75% “non-ACS chest pain”
 No gold standard for diagnosis
 Almost no follow-up data
 Many have atypical symptoms
 Missed MI rates (2-3%) (4)
 Missed MI associated with 2x higher mortality (4,)
http://www.cdc.gov/nchs/data/databriefs/db43.pdf JAMA. 1993;270:1211–1216 Medicine 2009;88:307–313 N Engl J Med. 2000;342:1187–1195
Ann Intern Med. 1998; 129:845– 855 N Engl J Med 2000; 342:1163–1170 Am J Cardiol 1991; 68:171–17 Am J Cardiol 1987;60:219-24
Life Threatening Causes of Chest Pain
 Myocardial infarction
 Unstable angina
 Takotsubo Cardiomyopathy
 Thoracic aortic dissection
 Pulmonary embolus
 Tension pneumothorax
 Oesophageal rupture
Assessment of Chest Pain:
Asking the Right Questions
 Is the chest pain likely due to myocardial ischemia ?
 Has there been an acute coronary event ?
 Is there a precipitating cause ? ie Type 2 MI
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Recent onset AF
Anemia / blood loss
Sepsis
Hypotension
 Are there high risk clinical features?
Q2: If troponin I results upon this patient's admission were
normal (0.02 ng/mL), what would be your next evaluation
and treatment steps?
a) Continue observing this patient and repeat troponin and ECG
tests
b) Consider additional diagnostic tests/biomarkers
c) Initiate phone consult with a cardiologist if available
Criteria for Acute Myocardial Infarction
 Detection of a rise and/or fall of cardiac biomarker
values (preferably cardiac troponin) with at least one
value above the 99th percentile upper reference limit
(URL) and with at least one of the following:
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Ischaemic symptoms;
ECG changes of new ischaemia (new ST-T changes or new LBBB);
Development of pathologic Q waves in the ECG:
Imaging evidence of new loss of viable myocardium or new
regional wall motion abnormality;
Identification of an intracoronary thrombus by angiography or
autopsy.
www.escardio.org/guidelines European Heart Journal (2012) 33:2551-2567
doi: 10.1093/eurheartj/ehs 184.
Applications of Troponin Testing
 Cardiac Troponin (cTn)
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Highly specific for myocardial injury
 Myocardial Injury
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NOT specific for Acute Coronary Syndromes with Ischemia
induced injury
Occurs in multiple other conditions Associated with worse
prognosis
ACS treatment not needed: May be harmful
High Sensitivity Troponin (hs cTn)
 eg Roche Cobas cTnT, Siemens Stratus Ultra cTnI
 Increased sensitivity for detection of ACS
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Patients with negative standard Tn and symptoms of ACS
64% hs cTnI +ve
 Increased diagnostic accuracy especially for patients
presenting early after symptom onset
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84% positive at presentation with <3hrs symptoms vs 55%
with previous Troponin T assay
 Potentially lower specificity for diagnosis of ACS
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Greater number of patients without ACS have elevated cTn
Highlights importance of clinical evaluation
Use of hs Troponin
 Use the 99th percentile of the ref population as cTn URL
 Diagnosis of AMI requires significant change of Tn with
serial testing.
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Significant change > 20% if baseline markedly elevated
If around URL 200% change needed
 Blood sampling at baseline and 3 hrs later.
 Repeat at 6hrs if 3hr value unchanged and clinical suspicion
is high
 cTn marker of myocardial necrosis and not specific maker
of AMI.
 Diagnosis of AMI only with significant change of cTn and
clinical scenario (symptoms and or ECG)
European Heart Journal 2011; 32, 2999-3054 (ESC Guidelines for Management of ACS in patients without ST elevation)
Elevations of Cardiac Troponin Values
Because of Myocardial Injury
INJURY RELATED TO PRIMARY MYOCARDIAL ISCHAEMIA
(TYPE 1 MI)
INJURY NOT RELATED TO MYOCARDIAL ISCHAEMIA
 Plaque rupture.
 Cardiac contusion, surgery, ablation, pacing, or
 Intraluminal coronary artery thrombus
defibrillator shocks.
 Rhabdomyolysis with cardiac involvement.
 Myocarditis.
 Cardiotoxic agents, e.g. anthracyclines, herceptin.
formation.
INJURY RELATED TO SUPPLY/DEMAND IMBALANCE OF
MYOCARDIAL ISCHAEMIA (TYPE 2 MI)
 Tachy-/brady-arrhythmias.
MULTIFACTORIAL OR INDETERMINATE MYOCARDIAL INJURY
 Aortic dissection or severe aortic valve disease.
 Heart failure.
 Hyperthrophic cardiomyopathy.
 Stress (Takotsubo) cardiomyopathy.
 Cardiogenic, hypovolaemic, or septic shock.
 Severe pulmonary embolism or pulmonary
 Severe respiratory failure.
 Severe anaemia.
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 Hypertension with or without LVH.
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 Coronary spasm.
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 Coronary embolism or vasculitis.
 Coronary endothelial dysfunction without
significant CAD.
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hypertension.
Sepsis and critically ill patients.
Renal failure.
Severe acute neurological diseases, e.g. stroke,
subarachnoid haemorrhage.
Infiltrative diseases, e.g. amyloidosis, sarcoidosis.
Strenuous exercise.
www.escardio.org/guidelines European Heart Journal (2012) 33:2551-2567
doi: 10.1093/eurheartj/ehs 184.
Q3: What is your risk-stratification scale/method of
choice?
a) TIMI
b)GRACE
Predicting Ischemic Outcomes
Indicators of Increased Risk for Recurrent Ischemic Events
ACS RISK
BACKGROUND RISK
 Clinical
 Multiple episodes of chest pain
 Heart failure / hypotension
 Refractory ischemia
 Age
 ECG
 ST segment shift
 T wave inversion > 2mm
 VT
 Renal dysfunction
 Biomarkers
 Troponin > reference level
 LV function
 Diabetes
 Pre-existing CAD
Early Risk Stratification in
Acute Coronary Syndromes
ED
 Clinical observations
 ECG on presentation
 Recurrent ischemia
 Bio-markers of myocyte injury
 Risk scores (TIMI or GRACE)
LATER
 Myocardial perfusion
 LV function
 Coronary anatomy
Risk Scores
HISTORY
TIMI
 Age
 Hypertension
 Diabetes
 Smoking
 ↑ Cholesterol
 Family history
 Documented CAD
GRACE
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Age
Severe angina
 Aspirin within 7 days
Heart rate
 Systolic BP
 Elevated creatinine
 Heart failure
 Cardiac arrest
Elevated markers
 ST-segment deviation
Elevated markers
 ST-segment deviation
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PRESENTATION
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GRACE = Global Registry of Acute Coronary Events; TIMI = Thrombolysis in Myocardial Infarction.
Antman EM, et al. JAMA 2000;284:835–42. Eagle KA, et al. JAMA 2004;291:2727–33.
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TIMI Risk Score for Prediction of Cardiac
Events in ED Patients with Chest Pain
 10 prospective cohort ED based studies with 17265 patients
 Linear relationship between TIMI risk score and cardiac
outcome
 TIMI score 0 - 1.8% (20/1000) had cardiac event by 30 d
 TIMI risk score provides guidance but should not be used as
sole means of determining patient disposition.
 Clinical assessment based on history, ECG and troponin should
be fully evaluated before using TIMI risk score
Hess et al: CMAJ 2010;182:1039
Bleeding Risk Assessment
 Bleeding risk factors similar to ischemia risk factors
 Identify patients at higher bleeding risk
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Prior bleeding history
Age (> 75)
Female gender
Small body weight (<65kg)
Renal dysfunction
References: www.barnabashealth.org/services/cardiac/.../cohenwhitepaper09.pdf
Q4:Which antiplatelet agent would you add to
ASA and why?
a) Clopidogrel
b) Prasugrel
c) Ticagrelor
Q5:Which anticoagulant would you choose and
why?
a) Unfractionated heparin
b) Low molecular weight heparin (enoxaparin)
c) Fondaparinux
Antiplatelet / Anticoagulant Therapy in ACS
Available antiplatelet and anticoagulant therapies According to Invasive Strategy
CLINICAL SCENARIO
EARLY INVASIVE
INITIAL CONSERVATIVE
ASPIRIN
ASPIRIN
UPSTREAM
ORAL ANTIPLATELET
Ticagrelor
 Clopidogrel
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Clopidogrel
 Prasugrel
 Ticagrelor
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Fondaparinux
 Enoxaparin
 Unfractionated heparin
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ANTICOAGULANT
PERIPROCEDURE
Ticagrelor
 Clopidogrel
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Fondaparinux
 Enoxaparin
 Unfractionated heparin
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(Adapted from http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?productid=954&pageaction=displayproduct)
PLATO Study Design
NSTEMI ACS (moderate-to-high risk)
STEMI (if primary PCI) (N=18,624) Clopidogrel-treated or naive; randomized <24 hours of index event 1,261 patients
underwent CABG on study drug for ≤7 days prior to surgery
CLOPIDOGREL
If pre-treated, no additional loading
dose; if naive, standard 300 mg loading
dose, then 75 mg qd maintenance;
(additional 300 mg allowed pre-PCI)
TICAGRELOR
180 mg loading dose,
then 90 mg bid maintenance;
(additional 90 mg pre-PCI)
6–12 months treatment
Primary endpoint: CV death + MI + Stroke
Primary safety endpoint: Total major bleeding
Recommendations for patients undergoing CABG:
Study drugs withheld prior to surgery – 5 days for clopidogrel and 24–72 hours fors ticagrelor.
Study drug be restarted as soon as possible after surgery and prior to discharge
Wallentin et al N Engl J Med 2009;361:1045-57
Comparison of Ticagrelor with Clopidogrel
Primary Endpoint : Cardiovascular Death, MI or Stroke
PLATO
CUMULATIVE
INCIDENCE (%)
13
12
11.7
Clopidogrel
11
10
9.8
9
Ticagrelor
8
7
6
5
4
 16%
 21%
MI
CV death
3
2
1
p=0.005
p=0.001
HR 0.84 (95% CI 0.77–0.92), p=0.0003
0
0
60
Wallentin et al N Engl J Med 2009;361:1045-57
120
180
240
300
360 DAYS
Non-CABG and CABG-related Major Bleeding
PLATO
KAPLAN-MEIER
ESTIMATED RATE
(% PER YEAR)
NS
9
7.9
8
Ticagrelor
Clopidogrel
7.4
NS
7
6
5
4
5.8
p=0.026
5.3
4.5
3.8
p=0.025
2.8
3
2.2
2
1
362 vs. 306
221 vs. 177
619 vs. 654
446 vs. 476
NON-CABG
PLATO MAJOR
BLEEDING
NON-CABG
TIMI MAJOR
BLEEDING
CABG
PLATO MAJOR
BLEEDING
CABG
TIMI MAJOR
BLEEDING
0
Wallentin et al N Engl J Med 2009;361:1045-57
Ticagrelor vs Clopidogrel
 Improved outcomes
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CV Death, MI, Stroke  (NNT 54)
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CV death 
 Benefit in STEMI, diabetes, reduced renal function
 Administered at first medical contact
 No harm with prior stroke (non hemorrhagic)
 Applicable in all ACS scenarios except fibrinolysis
 Off target adverse effects uncommon and mild
Q6:This patient returns to the ER 5 days later complaining of the
shortness of breath. How would you manage this patient upon
ER readmission?
a) Discontinue ticagrelor
b) Assess for heart failure and advise continuation of ticagrelor
c) Administer diuretic
Q7: If the patient had bradycardia (HR=43bpm) and a history of
sick sinus syndrome would this change your choice of
antiplatelet therapy?
a) Yes
b) No
Off Target Adverse Effects of Ticagrelor
 Dyspnea
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PLATO Ticagrelor 13.8% placebo 7.8%, 0.8% discontinued
ONSET OFFSET Ticagrelor 38.6%, clopidogrel 9.3%, placebo 8.3%
• Most mild, lasted < 24hrs, occurred within 1st week
Evaluate for signs of heart failure, no need to stop ticagrelor
 Ventricular pauses
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Holter monitoring in 2866 PLATO patients
1st week: pauses >3 secs ticagrelor 5.8%, clopidogrel 3.6%
Usually occurred during sleep,
No clinical consequences
After 1 month no pauses
Brilinta® (ticagrelor) Product Monograph, Date of Preparation: March 07, 2013; Wallentin et al N Engl J Med 2009;361:1045-57
Initiating Ticagrelor from Clopidogrel in
Nonresponders
IPA (20μmol/L 100
Adp-induced
Maximum 90
Aggregation) %
80
Clopidogrel
Ticagrelor
Ticagrelor
Clopidogrel
70
60
50
40
30
20
10
0
0 .5 1 2 4 8 hr
Day 1
PERIOD 1
Gurbel et al: Circulation 2010; 121:1188-1199
0 2 4 8 hr
Day 14
CROSSOVER
0 .5 1 2 4 8 hr
Day 15
PERIOD 2
0 2 4 8 hr
Day 28
NSTE ACS Management
 Identify from history, ECG and cTn
 Initiate treatment with dual antiplatelet therapy with
ASA + clopidogrel, or ASA + ticagrelor.
 Initiate anticoagulation with UFH, enoxaparin or
fondaparinux
 Patients with high risk ACS will usually follow an early
invasive management strategy