Acute Coronary Syndromes

1
Acute Coronary Syndromes

• Adam Oster, R4.
• Dr. Gill Curry, FRCP
• Core Rounds.
• July 8, 2004.

2
Topics

• Master of the ECG
• Evidence for various therapeutic interventions
• NSTEMI Risk Stratification
• Thrombolysis
• AMI in LBBB
• Pre-hospital lytics
• Cardiogenic shock

3
ACS Rounds

• 55M with atypical chest pain for 60mins

4
Hyperacute T waves
5
Hyperacute T waves

• Early sign of infarct
• Normal T lt7mm
• Hyperacute gt8mm
• Ischemic are more symmetric
• Upgoing side still slopes up gradually
• Other Causes
• Hyperkalemia (steep and sharp)
• LVH
• LBBB

6
Master of the ECG

• Progression of changes

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STE
8
Evolving STEMI
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Evolving STEMI
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Post-STEMI 3 weeks
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Case
12
Case
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Case
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Role of the 15 lead

• Inferior MI
• RV infarct occurs in 25 of inferior MIs
• Different therapeutic and resuscitation needs
• Posterior MI
• Dorsal region of LV
• Usually LCX or RCA-posterior descending branch

15
Limitations of the ECG

• Specificity approx 50 for ischemia
• The normal or non-diagnostic ECG

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Special ECGs
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LM Disease
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Wellens Syndrome
19
Wellens Syndrome T Wave Inversion
20
Pope et al. Missed Diagnoses of Acute Cardiac
Ischemia in the Emergency Department. New England
Journal of Medicine vol. 342, no. 16, 2000.

• 10 689 patients
• Data collected for 30d (hospitalised patients) or
  at 24 to 72hrs for non-hospitalised patients
• Outcomes assigned by physicians at study sites
  using pre-defined criteria

21
Pope et al. Missed Diagnoses of Acute Cardiac
Ischemia in the Emergency Department. New England
Journal of Medicine vol. 342, no. 16, 2000.

• Final Diagnosis
• 1866 (17) ACI
• 894 (8.5) AMI
• 972 (9) unstable angina
• 21 non-ischemic cardiac problem
• 55 non-cardiac

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Pope et al. Missed Diagnoses of Acute Cardiac
Ischemia in the Emergency Department. New England
Journal of Medicine vol. 342, no. 16, 2000.

• 22 missed unstable angina (2.26)
• MC diagnosis
• stable angina, atypical chest pain

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Pope et al. Missed Diagnoses of Acute Cardiac
Ischemia in the Emergency Department. New England
Journal of Medicine vol. 342, no. 16, 2000.

• 19 missed AMIs (2.1 of 894)
• MC diagnosis
• non-cardiac chest pain, pulmonary conditions and
  stable angina

24
Pope et al. Missed Diagnoses of Acute Cardiac
Ischemia in the Emergency Department. New England
Journal of Medicine vol. 342, no. 16, 2000.

• Factors associated with non-hospitalisation for
  patients with missed ACI
• female
• lt55
• non-white
• chief complaint of SOB
• normal ECG
• 30d adjusted risk of mortality 1.7 times higher
  if not hospitalised (95 CI 0.7 to 5.2)

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AMI Mortality
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3 Cases of Chest Pain

• 50M with 1hr of RSCP. No known CAD.
• No DM/HTN/FHx. Smoker.
• ECG normal. 10hr TnT neg
• 65F with 120mins RSCP. No known CAD.
• T2DM/HTN/recent non-smoker.
• ECG non-specific. 10hr TnT neg.
• 74M with 3hrs RSCP
• prior 4xCABG, daily ASA.
• ECG nil acute, TnT positive

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ACS Risk Stratification
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Thrombolysis in Myocardial Infarction
(TIMI)Risk Stratification

• Antman et al. JAMA. 2000. Vol. 284, No.7.
• TIMI RS based on data from TIMI 11b (N3910) and
  ESSENCE (N3171)
• Test cohort (TIMI UFH)
• Validation cohort (TIMI and ESSENCE enoxaparin
  groups and ESSENCE UFH)
• TIMI RS derived in test cohort

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TIMI Risk StratificationAntman et al. JAMA.
2000. Vol. 284, No.7.

• Endpoints
• all-cause death, new or recurrent MI or UR at 14d
  post-randomisation
• Eligibility (1 of following)
• admitted patients who presented within 24hrs with
  symptoms of unstable angina/NSTEMI
• transient STE or STD or 0.05mV (TIMI) or 0.01mV
  (ESSENCE)
• known CAD
• increased Troponin

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TIMI Risk StratificationAntman et al. JAMA.
2000. Vol. 284, No.7

• All patients received ASA
• randomised to enoxaparin or UFH
• Derivation cohort
• tested 12 candidate variables
• age ST deviation
• at least 3 CAD risk factors gt2 anginal events in
  24hrs
• significant coronary stenosis use of ASA in last
  7d
• prior MI elevated cardiac markers
• prior CABG prior history of CHF
• prior PTCA

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TIMI Risk StratificationAntman et al. JAMA.
2000. Vol. 284, No.7

• Derivation cohort
• 7 variables remained statistically significant
  after multivariate analysis
• Age gt65
• at least 3 CAD RF
• STD
• severe anginal symptoms
• prior stenosis gt50
• use of ASA over previous 7d
• elevated serum cardiac markers

32
TIMI Risk StratificationAntman et al. JAMA.
2000. Vol. 284, No.7

• Small numbers of patients in extreme risk scores
  required combining
• criteria of known stenosis gt50, insensitive to
  missing data and remained a significant predictor

33
TIMI Risk StratificationAntman et al. JAMA.
2000. Vol. 284, No.7

• Validation Phase
• different rate of increase for rate of composite
  endpoint in UFH vs enoxaparin
• merged the databases
• TIMI RS and treatment were both significant
  predictors of risk of the composite endpoint

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TIMI Risk StratificationAntman et al. JAMA.
2000. Vol. 284, No.7

• Predicting the individual components of the
  composite endpoint
• all statistically sig.

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TIMI Risk StratificationAntman et al. JAMA.
2000. Vol. 284, No.7

• Caveats and Critique
• tested on admitted patients with unstable
  angina/NSTEMI
• Validation Phase not prospective
• cohort who qualified for enrolment in a phase
  III study ?generalisabilty to all-comers with
  chest pain
• enrolment criteria for TIMI 11b changed during
  the trial
• duration of treatment different between UFH
  (3-8d) and enoxaparin (8d or hospital discharge)
• elevated CKMB was both a predictor of an endpoint
  as well as part of the definition of an endpoint
• CKMB was the marker in TIMI but now use Troponin
  without study to prove similarly predictive

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TIMI Risk StratificationAntman et al. JAMA.
2000. Vol. 284, No.7

• Support
• consider using on chest pain patients to be
  admitted
• simple to use and to communicate to consultants
• cannot use to determine who is at low risk
• cannot use to determine who is safe for discharge
  

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How Predictive are Routine Historic Features?

• Goodacre et al. How Useful are Clinical Features
  in the Diagnosis of Acute, Undifferentiated Chest
  Pain? Academic Emergency Medicine, vol. 9, no. 3,
  2002.
• Prospectively evaluated 893 CPOU (normal ECG, no
  CHF or arrhythmia)
• ST seg monitoring, troponin T gt6hrs, /-EST or
  thallium
• F/U at 3d and 6mo, 12mo
• Endpoints AMI at presentation and ACS (AMI at
  any time, pos. EST cardiac death, arrhythmia,
  revascularisation procedure)
• Assessed predictive power of routine historic
  features

38
Goodacre et al. How Useful are Clinical Features
in the Diagnosis of Acute, Undifferentiated Chest
Pain? Academic Emergency Medicine, vol. 9, no. 3,
2002.
Features Predictive of AMI
39
Goodacre et al. How Useful are Clinical Features
in the Diagnosis of Acute, Undifferentiated Chest
Pain? Academic Emergency Medicine, vol. 9, no. 3,
2002.
Features Predictive of ACS
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Once Risk StratifiedWhat to give?

• ASA
• Heparin/LMWH
• hirudin
• Bblocker
• CCB
• Nitro
• Morphine
• O2
• Lytic
• Clopidegril (plavix)
• G2b3a
• Bed Rest

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NSTEMI

• Acute rupture of plaque
• Fibrin and platelets
• Incomplete occlusion of CA
• ?chlamydial
• Inflammatory reaction
• Shear forces

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Pharmacology...Better Living Through Chemistry
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O2

• Makes intuitive sense since imbalance between O2
  demand of myocardium and supply
• Hypoxemia in AMI most likely caused by V/Q
  mismatch from LV dysfunction
• Evidence to support routine use is weak
• Reduces amount of STE in precordial leads with
  anterior MI
• Madias, et al. Circulation 1976.

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Anti-Platelet Therapy

• ASA
• Clopidegril
• 2b3a

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ASA

• ISIS-2
• Randomised AMI to normal therapy or ASA or
  streptokinase
• Reduction in mortality with ASA or strepto
• ASA RRR 23
• NNT 20 to save 1 life in STEMI
• Benefit and risk profile better than thrombolytic
  since you can give ASA to virtually all with ACS

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ASA

• NSTEMI
• RRR 50
• ARR 3
• NNT death/MI 30

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ASA

• ASA
• 160-325mg to chew ASAP
• All trials have shown mortality benefit that
  extends to 2 years
• Contraindications
• Allergy??
• Active bleeding (GI, retinal)
• Hemophilia

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Putting it all together
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Anti-platelet therapy

• Clopidogrel
• CAPRIE (1996), RCT ASA vs Plavix (N19,185)
• 3 year ischemic stroke, MI or death ARR 0.5
  (NNT 200)
• Plavix equal to ASA but increased side effects
  (diarrhea, rash, GI bleed)

50
Anti-platelet therapy

• Clopidogrel
• CURE trial (2001) RCT Plavix ASA vs ASA
• UA/NSTEMI within 24 hr
• Death, MI, or stroke 3 and 12 month ARR 2.2
  (NNT 45)
• Excess in major bleed of 1 (NNH 100)
• Risk of bleed with CABG increased in 1st 5 days
• Recommended in UA/NSTEMI when noninvasive course
  is anticipated
• BOTTOM LINE appears to work but not for us to
  start in the ED

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Anti-platelet therapy

• GPIIbIIIa Receptor Antagonists
• Inhibits the cross-linking of platelets by
  fibrinogen

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GPIIbIIIa RA

• EPIC (abcixamab) NEJM 1994
• PRCT, N2,099 pts
• High risk pts going for PCI (AMI, USA)
• Reopro(bolus, bolus infusion) vs placebo
• Placebo vs bolus similar
• F/U 30 days
• Bolus/infusion lower rate triple end-point
  (Death, MI or urgent revascularization) 8.3 vs
  12.8 (ARR 4.5, RRR 35)
• 2 fold increase in major bleeds 14 vs 6.6 (ARI
  7.4, RRI 112!!!

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GPIIbIIIa RA

• CAPTURE (abcixamab) Lancet 1997
• PRCT, N1050 pts (stopped early)
• Pts with refractory USA, after cath and before
  plasty
• Reopro vs placebo , 18-24hrs before plasty, and 1
  hr after
• F/U 30 days then 6 months
• Composite endpoint at 30 days(Death, MI, urgent
  intervention ) 2.6 vs 5.5 (ARR 2.9, RRR 53)
• At 6 months no difference! (decreased early
  events only)
• Major bleeding 3.8 vs 1.9 (ARI 1.9, RRI 50)

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GPIIbIIIa RA

• CAPTURE (substudy)
• Predictive value of TnT
• Increased TnT(gt0.1 ng/ml) 30.9
• F/U 6 months Death or MI
• TnT ve
• Reopro 9.5 vs placebo 23.9 (ARR 14.4, RRR 60
• TnT ve
• Reopro 7.5 vs 9.4 (not significant)
• Conclusion TnT ve identifies a high risk
  population that seems to benefit from GIIb-IIa

55
GPIIbIIIa RA

• PRISM-PLUS (tirofiban) NEJM 1998
• PRCT, N1,570 pts
• Non-ST segment elevation ACS and likely to go to
  catheterization
• Heparin vs tirofiban vs combination
• Tirofiban alone arm stopped (increased mortality
  at 7 days)
• F/U 7 and 30 days and 6 months
• Composite endpoint (Death, MI or recurrent
  ischemia) 7 days 12.9 vs 17.9 (p0.004), 30
  days not significant, 6 months 27.7 vs 32.2
  (p0.02)

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GPIIbIIIa RA

• PURSUIT (eptifibatide)
• PRCT, N10,948 pts
• Eligible if ECG changes transient ST elevation,
  ST depression, T wave inversion, or positive CKMB
• Eptifibitide vs placebo
• F/U 30 days and 6 months
• Double endpoint (Death or MI) 30 days 14.2 vs
  15.7 (ARR 1.5, RRR 10), 6 months 12.1 vs
  13.6 (ARR 1.5, RRR 11)
• Medical Management US benefit, Europe and Latin
  America no benefit
• Didnt work in females!!!!!

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GPIIbIIIa RA

• GUSTO IV
• PRCT, N7800 pts
• ECG changes, ve troponin level
• Early revascularization strongly discouraged
• Abcixamab vs placebo (24-48 hr infusion)
• No difference in MI or Death

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GPIIbIIIa RA

• BOTTOM LINE
• They are definitely indicated as an adjunct to
  PCI
• Role in UA/NSTEMI is questionable, there appears
  to be a small reduction in death or MI in high
  risk groups (ongoing or recurrent pain, dynamic
  ST changes)
• Not enough evidence for us to start in the ED

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Heparins

• Does heparin add anything in addition to ASA?
• Ollier, et al. Meta-analysis. JAMA 1996
• small 33 RRR in MI
• NNT 40-80
• Barely statistically significant
• All high risk patients

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Anti-thrombotic therapy

• Unfractionated Heparin
• Theroux et al (1993) RCT ASAhep vs ASA
• Decreased rates of MI (fatal and nonfatal) 3
  (NNT 33)
• RISC (1990) ASA vs UFH vs UFH ASA
• ASA UFH had lowest events in 1st 5 days

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Anti-thrombotic therapy

• LMWH
• ESSENCE (1997) RCT enoxaparin vs UFH
• No difference in mortality
• Composite endpoint of death, MI or recurrent
  angina, ARR 3.2 (NNT33)
• TIMI 11B (1999) RCT enoxaparin vs UFH
• Composite endpoint death, MI, urgent need for
  PTCA, ARR 2.1 (NNT 50)
• 2 trials (1 dalteparin, 1 nadroparin) had neutral
  or unfavorable trends

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Heparin

• Use in moderate to high risk patients
• NNH 40
• Significant bleed
• thrombocytopenia

63
B-Blockade

• Shown to decrease all cause mortality by 2.6 if
  started within 5-21days of infarct (NNT 38)
• early treatment
• Metoprolol 15 mg vs placebo f/u at 3 month, 36
  RRR of death
• TIMI IIB showed lower reinfarction or recurrent
  CP
• If HR gt 70 and BP can tolerate give Metoprolol
  5-15 mg iv

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Nitro

• Intuitively should help
• Combat vasospasm
• Dilate coronary arteries improving perfursion
• Reduce pre-load reducing myocardial O2
  consumption
• Afterload reduction

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Nitro

• No mortality benefit clearly established
• Shown to decrease post infarct angina
• Give sl to patients with ischemic sounding CP
  unless SBP lt 90, HR lt 50, tachycardia, or
  suspected RV infarct

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Case

• 64F no known CAD
• 2 hrs atypical chest pain after mowing lawn.
• No cardiac RF
• ECG normal
• c/o 6/10 pain
• 3/10 post 3 sprays nitro

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Response to nitro

• Annals of Internal Medicine 2003, Dec 16
  139979-86.
• Enrolled 459 patients prospectively admitted with
  chest pain. Observational study.
• Use a combined Gold Standard for active CAD and
  no active CAD
• Defined response to nitro as gt50 decline in pain
  at 5mins post-dose
• All pts followed for 4 months after index visit

68
Annals of Internal Medicine 2003, Dec 16
139979-86.

• Active CAD
• 35 responsive (49/141)
• No active CAD
• 41 responsive (113/275)

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Annals of Internal Medicine 2003, Dec 16
139979-86.
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Annals of Internal Medicine 2003, Dec 16
139979-86.
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Annals of Internal Medicine 2003, Dec 16
139979-86.

• Limitations
• Self-reported pain (reporting bias)
• Unvalidated pain-scale (reliability)
• Non-blinded physicians (work-up bias)
• 43 pts with chest pain of unclear origin

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Management of AMI

• Thrombolytics
• Goal door-to-needle time of 30 minutes
• FTT Trial (N58,000)
• No survival benefit after 12 hours
• ARR 2, NNT 40-50

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Management of AMI

• Fibrinolytics started
• First hour
• Second hour
• Third hour
• 3-6 hour
• 6-12 hour
• 12-24 hour

• Additional lives saved per 1000 pts treated
• 65
• 37
• 29
• 26
• 18
• 9

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To Lyse? Or not to
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Lysis?
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Lysis?
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Lysis?
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Lytic Criteria

• Canadian Consensus Conference on Coronary
  Thrombolysis 1994 Recommendations.
• Indications
• gt30mins chest pain and
• At least 1mm STE in at least 2 limb leads or
• At least 2mm in at least 2 adjacent precordial
  leads or
• Complete BBB
• Within 12 hrs of symptoms
• Target time lt1hr from patient arrival
• Benefit extends to those 75 and older

80
Canadian Consensus Conference on Coronary
Thrombolysis 1994 Recommendations

• Contraindications
• Absolute
• Pericarditis
• Dissection
• Active bleeding
• Relative
• Any time cerebral bleed, malignancy/AVM
• lt6mo GI/GU bleed
• Severe uncontrolled hypertension

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Management AMI - PTCA

• Meta-analysis Weaver et al
• 10 RCT, N 2606
• ARR 30 day mortality PTCA vs lytic 2.1, NNT
  50
• ARR 30 day mortality or reinfarction 4.7 NNT
  21

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Management AMI - PTCA

• Primary angioplasty vs (any agent) thrombolysis
• Reduction in 30d mortality (7 v 9)
• non-fatal reinfarction (3 v 7)
• stroke (1 v 2)
• and a combination of these three end points (8 v
  14)
• (P lt 0.001 for all comparisons).

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Management of AMI - PTCA
84
Interventions vs 30d Mortality
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Local Initiatives

• STEMI
• ASCENT-IV

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Local Practice

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ASCENT - IV

• 55M with RSCP for 4hrs at PLC
• STE anteriorly
• Delay to PCI of approx 90mins
• ??
• ASCENT IV

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50F with chest pain and this ECG
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50F with chest pain and this ECG
90
AMI in LBBB
91
Sgarbossa EB et al, NEJM 1996334481-7

• Derived rule from GUSTO-1 subgroup with
• Enzyme proven AMI
• LBBB on initial ECG
• Compared to databank of LBBB with cath-proven CAD
  but without chest pain during ECG
• ECGs analyzed by 4 blinded readers

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Sgarbossa EB et al, NEJM 1996334481-7

• Univariate analysis
• 1mm or more elevation concordant with QRS
• Sens 73 (64-80), specificity 92 (86-96)
• LR 9.54 (3.1-17.3)
• 5mm or more STD discordant with QRS
• Sensitivity 31 (23-39) specificity 92 (85-96)
• LR 3.63 (2.0-6.8)

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Sgarbossa EB et al, NEJM 1996334481-7
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Sgarbossa EB et al, N Engl J Med 1996334481-7

• For a specificity of 90, need a score of 3 or
  more.

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Sgarbossa EB et al, NEJM 1996334481-7

• Validation Sample (in cohort of 45 pts)
• Score /gt3
• Sens 36 (compared to 73 in derivation cohort)
• Spec 96
• LR 9.0
• PPV 88
• NPV 61

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Since Sgarbossa

• Kontos et al. Annals of Emergency Medicine Vol
  37, no.5, 2001.
• Prospective evaluation of all chest pain patients
  (n7725)
• 2.4 LBBB (n182)
• AMI in 13 of these (n24)
• Sgarbossa performance
• Concordant STE 1mm sens 8, spec 100 (98-100)
• PPV 100 (33-100), NPV 88 (82-92)
• STD 1mm in V1-3 sens 17, spec 100 (98-100
• PPV 100 (50-100), NPV 89 (83-93)
• STE discordant 5mm sens 21, spec 93 (88-96)
• PPV 31 (14-56), NPV 89 (83-96)

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Sgarbossa and Kontos

• Comments and Take Home
• Low prevalence of AMI in pts with LBBB
• ECG criteria occur infrequently and have low PPV
• Only 11/24 of AMI with LBBB met 1 of the 3
  criteria
• Highest specificity criteria was gt1mm concordant
  STE
• Very few (approx 3) meet any of the criteria
• Cannot use as rule-out test

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Case

• 67F with 3hrs RSCP
• ECG is non-specific
• TnT neg

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Troponin T

• Test Characteristics

• Troponin increase levels?
• Ischemia/ infarction
• Cardiomyopathy
• Electrical injury
• Pericarditis
• Myocarditis
• Cardiac contusion
• Hypertensive emergencies
• End- stage renal failure
• Pulmonary embolus

100
Troponin T

• Time to detection
• 2-6hrs
• Peaks
• 10hrs to 24hrs
• Time to normalisation
• 10-15days

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Troponin
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Troponin T

• Troponin should NOT determine disposition
• General Numbers to remember
• 6 -----------------gt 60 sensitive
• 8 -----------------gt 80 sensitive
• 10 -----------------gt 90 sensitive
• Patients with TnT and CKMB have worse
  prognosis (increased death and CV events at 30
  days)

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Case

• 55M with ESRD
• HD 3/week
• No previous IHD
• Cath 4 years ago demonstrated non-occlusive
  disease
• 6hrs atypical chest pain
• TnT .15

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TnT in RF

• Tricky
• Some research in the area
• Starting points
• Cardiovascular death makes up 50 of death in
  ESRD
• Prevalence of CAD is approx 75
• Higher risk of silent ischemia and atypical
  presentations
• ECG may also be difficult to interpret d/t LVH

105
TnT in RF

• Hypotheses on why elevated
• Uremic cardiomyopathy
• Clinically silent micro-infarctions
• LVH
• Unlikely d/t decreased renal clearance
• Similar molecular wt as albumin
• Post-Tx still have elevated TnT

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TnT in RF

• Elevation What does it mean?
• No true GS of IHD in ESRD
• Lower sens/spec of stress testing
• Less prevalence of cath in this population
• Have to rely on outcomes

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TnT in RFElevation What does it mean? No
suspicion of ACS.

• Significant difference in 1 yr cardiovascular
  mortality gt0.1
• Nephrol Dial Transplant 19991419617
• 102 patients with ESRD without any clinical
  evidence of acute ischemic heart disease
• Troponin T gt 0.1 ng/ml was strongly associated
  with all cause mortality
• TnT 0.05 ng/ml was associated with fatal
  cardiovascular events.
• This association was independent of baseline
  presence of heart disease.
• All patients with non-detectable TnT were alive
  at follow up.
• Circulation 2000 10219649

108
TnT in RFElevation What does it mean? No
suspicion of ACS.

• 244 patients on chronic hemodialysis for up to 34
  months.
• Troponin T significantly associated with death
  from all causes
• strongest association for TnT values above 0.1
• A trend of increasing TnT measurements during
  longitudinal follow up was also predictive of
  progression of cardiac disease and all-cause
  mortality

109
TnT in RFElevation What does it mean?
Suspicion of ACS.

• 7,033 patients from the GUSTO-IV
• prognostic value of cardiac TnT was not
  diminished in patients presenting with renal
  insufficiency and suspected ACS
• Patients with positive TnT and renal
  insufficiency had the highest overall risk of
  cardiac death or acute MI
• N Engl J Med 20023462047-52.

110
TnT in RFElevation What does it mean?
Suspicion of ACS.
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TnT in RFElevation What does it mean?
Suspicion of ACS.
112
TnT in RFElevation What does it mean?
Suspicion of ACS.
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Case

• 60M with chest pain for 12hrs
• STE anteriorly
• BP 80/50, HR 120
• Sats 90 NRB

114
Cardiogenic shock

• Complicates 7-10 of AMI
• 70-80 mortality
• Diagnosis
• SBPlt 90mmHg
• Evidence of end organ hypoperfusion (cool
  extremities, oliguria, altered mentation)

115
Management cardiogenic shock

• Oxygenation and ventilation
• Improve systolic function
• Catecholamines (dopamine, dobutamine if BP
  tolerates)
• IABP
• revascularization

116
Cardiogenic shock PTCA vs lytic

• SHOCK (1999)
• RCT PTCA vs lytic, N 302
• 2.7 cross over to PTCA group within 54 hrs
• 9.8 ARR at 30 day mortality (not stat sig)
• 13 ARR at 6 month mortality (NNT 8)

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Pre-hospital Lytics

• 45M with 45mins severe RSCP
• Medics patch in that this guy has widespread
  anterior STE and they want to give lytic
• Transport time 30-45mins
• What do you say?

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• lt6hrs chest pain
• N840 to PCI or pre-hospital lytic
• Pre-specified sub-groups
• lt2hrs, gt2hrs

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