Transcript Acute Coronary Syndrome

Acute Coronary
Syndrome
Dr. S.A. moezzi
ACS Overview
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Overview of ACS
Assessment of “Likelihood of ACS”
Early Risk Stratification
Invasive vs Conservative Strategy
Pharmacotherapy
Long-term Therapy/Secondary Prevention
Scope of the Problem

5 million ER visits nationwide for CP
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800,000 experience an MI each year
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213,000 die from their event
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½ of those die before reaching the ER
Pre-CCU, mortality for MI was >30%
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Fell to 15% with CCU
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With current interventions, in hospital mortality of
STEMI is 6-7%
Overview of ACS
Acute Coronary
Syndromes*
1.57 Million Hospital Admissions - ACS
UA/NSTEMI†
STEMI
1.24 million
0.33 million
Admissions per year
Admissions per year
*Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA.
Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171.
Acute Coronary Syndrome (ACS)

Definition: The spectrum of acute ischemia
related syndromes ranging from UA to MI
with or without ST elevation that are
secondary to acute plaque rupture or plaque
erosion.
[----UA---------NSTEMI----------STEMI----]
Pathophysiology of Stable Angina and ACS
Pathophysiology
ACS
•Anemia
•Plaque rupture/clot
Increased O2 Demand
O2 supply/demand mismatch→Ischemia
Myocardial ischemia→necrosis
Angina
•Flow- limiting stenosis
Asymptomatic
Decreased O2 Supply
Pathophysiology of ACS
Evolution of Coronary Thrombosis
Unstable
Angina
Non occlusive
thrombus
Non specific
ECG
Normal cardiac
enzymes
NSTEMI
Non-occlusive
thrombus
sufficient to cause
tissue damage & mild
myocardial necrosis
STEMI
Complete thrombus
occlusion
ST elevations on
ECG or new LBBB
ST depression +/T wave inversion on
ECG
Elevated cardiac
enzymes
Elevated cardiac
enzymes
More severe
symptoms
STEMI

Name 3 situations in which you cannot
diagnose STEMI
STEMI
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Name 3 situations in which you cannot
diagnose STEMI
Left Ventricular Hypertrophy
 Chronic or Rate Dependent LBBB
 Paced Rhythm
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Diagnosis of ACS

At least 2 of the
following
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History ( angina or angina
equivalent)
Acute ischemic ECG changes
Typical rise and fall of cardiac
markers
Absence of another identifiable
etiology
Likelihood of ACS by Hx/PE
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History/Examination
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Suggesting AMI
Pain in Chest or Left Arm
CP Radiation
 Right Shoulder
 Left Arm
 Both Left & Right Arm
Diaphoresis
3rd Heart Sound
SBP < 80 mm Hg
Pulmonary Crackles
Panju AA. JAMA. 1998;280:1256.
LR 2.7
LR 2.9 (1.4-6.0)
LR 2.3 (1.7-3.1)
LR 7.1 (3.6-14.2)
LR 2.0 (1.9-2.2)
LR 3.2 (1.6-6.5)
LR 3.1 (1.8-5.2)
LR 2.1 (1.4-3.1)
Likelihood of ACS by Hx/PE

Clinical Examination –
 Pleuritic Chest Pain
 Sharp or Stabbing Pain
 Positional Chest Pain
 Reproducible Chest Pain
Against AMI
LR 0.2 (0.2-0.3)
LR 0.3 (0.2-0.5)
LR 0.3 (0.2-0.4)
LR 0.2-0.4
Panju AA. JAMA. 1998;280:1256.
Risk Stratification by ECG
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Simple, quick, noninvasive tool
Universally available, cheap
Correlates with risk and prognosis
Guides treatment decisions
Can identify alternative causes
Risk Stratification by ECG
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ECG Findings and Associated LR for AMI
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New ST-E > 1mm
New Q waves
Any ST-E
New Conduction Defect
New ST-D
LR 5.7-53.9
LR 5.3-24.8
LR 11.2 (7.1-17.8)
LR 6.3 ( 2.5-15.7)
LR 3.0-5.2
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NORMAL ECG
LR 0.1-0.4
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Panju AA. JAMA. 1998;280:1256.
Risk Stratification by ECG
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1-8% AMI have a normal ECG
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Only Approx 50% of AMI patients have
diagnostic changes on their initial ECG
Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.
Risk Stratification by ECG
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1 ECG cannot exclude AMI
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Brief sample of a dynamic process
Small regions of ischemia or infarction may be
missed
Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.
How Sensitive is the ECG Alone?
How Predictive is NTG response?
Timing of Release of Various Biomarkers After
Acute Myocardial Infarction
Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3 rd ed. Rochester, MN:
Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80.
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5.
Risk Stratification by Troponin
7.5 %
Mortality at 42 Days
8
7
6.0 %
6
5
4
3
2
1
1.0 %
831
3.4 %
3.7 %
148
134
1.7 %
174
50
67
0
0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0
Cardiac troponin I (ng/ml)
 9.0
National Academy of Clinical Biochemistry Laboratory Medicine (NACB)
and the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of
Myocardial Infarction
 • Cardiac troponin is the preferred marker for the diagnosis
of MI and for risk stratification. CK-MB by mass assay is an
acceptable alternative when troponin in not available.
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• CK-MB was preferred by the NACB for the detection of
reinfarction early after the index event
increased sensitivity and specificity of cTn should make it the
marker of choice it is unnecessary to obtain both values.
Cardiac troponins I and T are equally useful.
Non ACS causes of Troponin Elevation
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac
surgery, after-interventional closure of ASDs)
Congestive heart failure (acute and chronic)
Aortic valve disease and HOCM with significant LVH
Hypertension
Hypotension, often with arrhythmias
Noncardiac surgery
Renal failure
Critically ill patients, especially with diabetes, respiratory failure
Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms)
Hypothyroidism
Coronary vasospasm, including apical ballooning syndrome
Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination,
Post-PCI
Pulmonary embolism, severe pulmonary hypertension
Sepsis
Burns, especially if TBSA greater than 30%
Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma
Acute neurologic disease, including CVA, subarchnoid bleeds
Rhabdomyolysis with cardiac injury
Transplant vasculopathy
Vital exhaustion
Modified from Apple FS, et al Heart J. 2002;144:981-986.
Combined Sensitivities for ACS
Unstable angina/NSTEMI cardiac
care

Evaluate for conservative vs. invasive strategy
based upon:
 Likelihood
of actual ACS
 Risk stratification by TIMI risk score
 ACS risk categories per AHA guidelines
Low
High
Intermediate
TIMI Risk Score
Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days
TIMI Risk Score
T: Troponin elevation (or CK-MB elevation)
H: History or CAD (>50% Stenosis)
R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II,
Active Smoker)
E: EKG changes: ST elevation or depression 0.5 mm concordant
leads
A2:Aspirin use within the past 7 days;
Age over 65
T: Two or more episodes of CP within 24 hours
Deciding between Early Invasive vs a Conservative Strategies
Definitive/Possible ACS
Initiate ASA, BB, Nitrates,
Anticoagulants, Telemetry
Early Invasive Strategy
• TIMI Risk Score >3
• New ST segment
deviation
• Positive biomarkers
•Hemodynamic instability
•Elecrical instability
•Refractory angina
•PCI in past 6 months
•CABG
•EF <40%
Coronary angiography
(24-48 hours)
Conservative Strategy
•TIMI Risk Score <3 (Esp. Women)
•No ST segment deviation
•Negative Biomarkers
Recurrent Signs/Symptoms
Heart failure
Arrhythmias
Remains Stable
↓
Assess EF and/or Stress Testing
↓
EF<40% OR Positive stress
Go to Angiography
Specifics of Early Hospital Care
Anti-Ischemic
Therapy
Anti-Platelet Therapy
Anticoagulant Therapy
Early Hospital Care
Anti-Ischemic Therapy
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Class I
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Bed/Chair rest and Telemetry
Oxygen (maintain saturation >90%)
Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart
failure, hypertension)
Oral B-blockers in First 24-hours if no contraindications.
(IV B-blockers class IIa indication)
Non-dihydropyridine Ca-channel blockers for those with
contraindication fo B-blockers
ACE inhibitors in first 24-hours for heart failure or
EF<40% (Class IIa for all other pts) (ARBs for those
intolerant)
Statins
Early Hospital Care
Anti-Ischemic Therapy
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Class III
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Nitrates if BP<90 mmHg or RV infarction
Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil
Immediate release dihydropyradine Ca-blockers in the
absence of B-Blocker therapy
IV ACE-inhibitors
IV B-blockers in patients with acute HF, Low output state
or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd
degree heart block, active asthma, or reactive airway
disease
NSAIDS and Cox-2 inhibitors
Early Hospital Care
Anti-Platelet Therapy

Class I
Aspirin (162-325 mg), non enteric coated
 Clopidogrel for those with Aspirin
allergy/intolerance (300-600 mg load and 75 mg/d)
 GI prophylaxis if a Hx of GI bleed
 GP IIb/IIIa inhibitors should be evaluated based on
whether an invasive or conservative strategy is
used
 GP IIb/IIIa inhibitors recommended for all
diabetics and all patient in early invasive arm

secondary prevention
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At present, the United States Food and Drug
Administration recommends daily doses of 75
to 325 mg,
the 2006 American College of Cardiology
/American Heart Association (ACC/AHA)
guidelines on recommends daily doses of 75 to
162 mg for secondary prevention [38].
The ACCP recommends a daily dose of 75 to
100 mg
Early Hospital Care
Anticoagulant Therapy
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Class I
Unfractionated Heparin
 Enoxaparin
 Bivalarudin
 Fondaparinux
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Relative choice depends on invasive vs
conservative strategy and bleeding risk
Early Hospital Care
Statin Therapy
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MIRACL Trial
Inclusion Criteria
3086 patients with Non ST ACS
 Total cholesterol <270 mg/dl
 No planned PCI
 Randomized to Atorvastatin vs Placebo
 Drug started at 24-96 hours
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Statin Evidence: MIRACL Study
Primary Efficacy Measure
Placebo
Cumulative Incidence (%)
15
17.4%
14.8%
Atorvastatin
10
Time to first occurrence of:
• Death (any cause)
• Nonfatal MI
• Resuscitated cardiac arrest
• Worsening angina with new
objective evidence and
urgent rehospitalization
5
Relative risk = 0.84
P = .048
95% CI 0.701-0.999
0
0
4
8
12
Time Since Randomization (weeks)
Schwartz GG, et al. JAMA. 2001;285:1711-1718.
16
Statin Evidence: MIRACL Study
Fatal and Nonfatal Stroke
Cumulative Incidence (%)
2
Placebo
1.5
1
Atorvastatin
0.5
Relative risk = 0.49
P = .04
95% CI 0.24-0.98
0
0
4
8
12
16
Time Since Randomization (weeks)
Waters DD, et al. Circulation. 2002;106:1690-1695.
S24
PROVE-IT Trial
All-Cause Death or Major CV Events
in All Randomized Subjects
30
Pravastatin 40mg
(26.3%)
25
20
%
with 15
Event
Atorvastatin 80mg
(22.4%)
10
16% RR
(P =
0.005)
5
0
0
3
6
9
12
15
18
21
Months of Follow-up
24
27
30
Summary of PROVE-IT Results
In
patients recently hospitalized within 10 days for an
acute coronary syndrome:
 “Intensive” high-dose LDL-C lowering (median LDL-C 62
mg/dL) compared to “moderate” standard-dose lipid-lowering
therapy (median LDL-C 95 mg/dL) reduced the risk of all cause
mortality or major cardiac events by 16% (p=0.005)
 Benefits emerged within 30 days post ACS with continued benefit
observed throughout the 2.5 years of follow-up
 Benefits were consistent across all cardiovascular endpoints,
except stroke, and most clinical subgroups
Invasive vs Conservative
Strategies
Invasive vs Conservative Strategy
Clinical Trials
ISARCOOL
VANQWISH (98)
ICTUS (05)
RITA-3 (02)
MATE
VINO
TIMI IIIB (94)
TRUCS
TACTICSTIMI 18 (01)
Weight of
the evidence
Conservative
Strategy Favored
N=920
No difference
N=2,874
FRISC II (99)
Invasive
Strategy Favored
N=7,018
How Early is Early?
Secondary Prevention
Class I Indications
Aspirin
 Beta-blockers: (all pts, slow titration with moderate to
severe failure
 ACE-Inhibitors: CHF, EF<40%, HTN, DM
(All pts-Class IIa) ARB when intolerant to ACE.
(Class IIa as alternative to ACEI)
Aldosterone blockade: An ACEI, CHF with either
EF<40% or DM and if CrCl>30 ml/min and K<5.0
mEq/L
 Statins
 Standard Risk Factor Management
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Long-Term Antithrombotic Therapy at Hospital
Discharge after UA/NSTEMI
New
UA/NSTEMI
Patient Groups at
Discharge
Medical Therapy
without Stent
ASA 75 to 162 mg/d indefinitely
(Class I, LOE: A)
Bare Metal Stent
Group
Drug Eluting
Stent Group
ASA 162 to 325 mg/d for at least 1
month, then 75 to 162 mg/d
indefinitely (Class I, LOE: A)
&
&
Clopidogrel 75 mg/d for at least 1
month and up to 1 year
(Class I, LOE:B)
Clopidogrel 75 mg/d at least 1
month (Class I, LOE: A) and up
to 1 year (Class I, LOE: B)
ASA 162 to 325 mg/d for at
least 3 to 6 months, then 75 to
162 mg/d indefinitely
(Class I, LOE: A)
&
Clopidogrel 75 mg/d for at
least 1 year (Class I, LOE: B)
Indication for
Anticoagulation?
Yes
Add: Warfarin (INR 2.0 to 2.5)
(Class IIb, LOE: B)
No
Continue with dual antiplatelet
therapy as above
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence.
Secondary Prevention
Class III
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Hormone Replacement Therapy
Antioxidants (Vit C, Vit E)
Folic Acid
Early Treatment with Clopidogrel
Shortcomings of the CURE Trial
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Conducted primarily at centers without routine
use of early invasive strategy
Only 462 (3.7%) patients enrolled from the
U.S.
44% had catheterization during index
hospitalization
Adverse event reduced only in nonfatal MI set
Major Bleeding rate of 9.6% among patients
who were administered clopidogrel within 5
days of CABG
Clopidogrel
Bleeding Risk and CABG
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“In hospitals in which patients with
UA/NSTEMI undergo rapid diagnostic
catheterization within 24 hours of admission,
clopidogrel is not started until it is clear that
CABG will not be scheduled within the next
several days. However, unstable patients
should receive clopidogrel or be take for
immediate angiography.”
Clopidogrel vs. Prasugrel
Prasugrel-Key Facts
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Contraindicated in pts with prior TIA/Stroke
Not recommended for patients >75 years
5 mg maintenance dose suggested in patients
<60 Kg, though this dose has not been studied
Summary
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ACS includes UA, NSTEMI, and STEMI
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Management guideline focus
Immediate assessment/intervention (MONA+BAH)
 Risk stratification (UA/NSTEMI vs. STEMI)
 RAPID reperfusion for STEMI (PCI vs.

Thrombolytics)
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Conservative vs Invasive therapy for UA/NSTEMI
Aggressive attention to secondary prevention
initiatives for ACS patients
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Beta blocker, ASA, ACE-I, Statin
Ten Points to Remember from the
2009 STEMI Guideline Update
Antman EM, Hand M,
Armstrong PW, et al.,
Ten Points to Remember
from the
2009 STEMI Guideline Update
1.
Patients routinely taking NSAIDs (except for
aspirin), both nonselective as well as COX-2
selective agents, before STEMI should have
those agents discontinued at the time of
presentation with STEMI because of the
increased risk of mortality, reinfarction,
hypertension, heart failure, and myocardial
rupture associated with their use.
Ten Points to Remember
from the
2009 STEMI Guideline Update
2.
Oral beta-blocker therapy should be initiated in the
first 24 hours for patients who do not have any of the
following:
a) Signs of heart failure
b) Evidence of a low output state
c) Increased risk for cardiogenic shock
d) Other relative contraindications to beta blockade
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PR interval > 0.24 seconds
Second- or third-degree heart block
Active asthma or reactive airway disease
Ten Points to Remember
from the
2009 STEMI Guideline Update
3.
STEMI patients presenting to a hospital with PCI
capability should be treated with primary PCI within
90 minutes of first medical contact as a systems goal.
4.
STEMI patients presenting to a hospital without PCI
capability and who cannot be transferred to a PCI
center and undergo PCI within 90 minutes of first
medical contact should be treated with fibrinolytic
therapy within 30 minutes of hospital presentation as
a systems goal unless fibrinolytic therapy is
contraindicated.
Ten Points to Remember
from the
2009 STEMI Guideline Update
A strategy of coronary angiography with intent to
perform PCI (or emergency CABG) is recommended
for patients who have received fibrinolytic therapy
and have any of the following:
5.
•
Cardiogenic shock in patients <75 years who are suitable
candidates for revascularization,
•
Severe congestive heart failure and/or pulmonary edema
(Killip class III), or
•
Hemodynamically compromising ventricular arrhythmias
Ten Points to Remember
from the
2009 STEMI Guideline Update
6.
Patients undergoing reperfusion with fibrinolytics
should receive anticoagulant therapy for a
minimum of 48 hours and preferably for the
duration of the index hospitalization, up to 8 days
(regimens other than unfractionated heparin [UFH]
are recommended if anticoagulant therapy is given
for more than 48 hours because of the risk of
heparin- induced thrombocytopenia with prolonged
UFH treatment).
Ten Points to Remember
from the
2009 STEMI Guideline Update
7.
Clopidogrel 75 mg per day orally should be added
to aspirin in patients with STEMI regardless of
whether they undergo reperfusion with
fibrinolytic therapy or do not receive reperfusion
therapy. Treatment with clopidogrel should
continue for at least 14 days.
8.
Every tobacco user and family members who
smoke should be advised to quit at every visit.
Ten Points to Remember
from the
2007 STEMI Guideline Update
9. For all post-PCI STEMI stented patients without
aspirin resistance, allergy, or increased risk of
bleeding, aspirin at a dose of 162-325 mg daily
should be given for at least 1 month after baremetal stent (BMS) implantation, 3 months after
sirolimus-eluting stent implantation, and 6 months
after paclitaxel-eluting stent implantation, after
which long-term aspirin use should be continued
indefinitely at a dose of 75-162 mg daily.
Ten Points to Remember
from the
2007 STEMI Guideline Update
10.
For all post-PCI patients who receive a drugeluting stent, clopidogrel 75 mg daily should be
given for at least 12 months if patients are not at
high risk of bleeding. For post-PCI patients
receiving a BMS, clopidogrel should be given for a
minimum of 1 month and ideally up to 12 months
(unless the patient is at increased risk of bleeding;
then it should be given for a minimum of 2 weeks).
ACC/AHA Guideline Classification System
Level of Evidence (LOE)
 LOE A – strong evidence
 Mult iple large randomized trials
 LOE B – Intermediate
 Limited # or small trials
 Nonrandomized studies/observational registries
 LOE C – Expert consensus/Opinion
Beta-blockers in STEMI

Class I - oral beta-blockers should be initiated within 24
hours* LOE B

Class IIa - reasonable to administer IV beta-blocker at the time
of presentation who are hypertensive* LOE B

Class III - IV beta-blockers should not be administered to
patients with any of the following* LOE A
* Contraindications include 1) signs of heart failure, 2) evidence of low output state,
3) risk for cardiogenic shock (age>70, SBP<120, sinus tach>110bpm, HR<60,
increased time since onset of STEMI), 4) or other relative contraindication
(PR>0.24s, heart block, active asthma)
UFH/ LMWH in STEMI
Class I - Patients receiving fibrinolytics should receive
anticoagulant therapy for a minimum of 48 hrs, LOE C.
Because of heparin induced thrombocytopenia, regimens other
than UFH are recommended for patients receiving
anticoagulant therapy > 48 hrs, LOE A.
DOSE:
 UFH - 60 U/kg (max 4000 U) bolus, then 12 U/kg per hr drip
 Enoxaparin - (Cr <2.5 men, <2.0 women)



For pts age <75 give 30mg IV bolus followed 15min later by 1 mg/kg
subq.
For pts >=75, no IV bolus and reduce subq dose to 0.75 mg/kg
Clopidogrel in STEMI

Class I - Clopidogrel 75mg/ day should be
added to ASA in pts with STEMI regardless of
fibrinolytic use LOE A

Class IIa - In patients < 75yo, it is reasonable
to consider a loading dose of 300mg LOE C
- recent studies suggest a loading dose of Plavix 600mg
Questions?