Acute Coronary
Syndrome #2
July 26, 2013
Class of
Recommendation
Class I: Benefit >>> Risk
Procedure or treatment
should be performed
Class IIa: Benefit >> Risk
It is reasonable to perform
procedure or treatment
Class IIb: Benefit ≥ Risk
It is reasonable to consider
procedure or treatment
Class III: Risk ≥ Benefit
Procedure or treatment
should not be performed
Level of Evidence
A
Data from randomized
clinical trials or metaanalysis
B
Data from single
randomized trial or
nonrandomized studies
C
Consensus of opinion
of experts, case studies
or standard of care
Percutaneous Coronary Intervention (PCI)
• Facilitated PCI: Strategy of full or half dose
•
fibrinolytic therapy with or without IIb/IIIa
receptor antagonist with immediate
transfer or planned PCI within 90 to 120
minutes.
Rescue PCI: Transfer for PCI of patients
who failed reperfusion with fibrinolytic
therapy.
2013 ACCF/AHA Guideline for STEMI, JACC 2013:61:
Coronary Angioplasty VS Fibrinolytic Therapy in Acute
Myocardial Infarction
Fibrinolysis
Door-to-Needle or
FMC to Needle
< 30 mins
Not PCI
capable
EMS Transport
Primary PCI
Door-to-Balloon or FMC
to Balloon ≤ 90 mins
PCI
capable
Coronary Angioplasty VS Fibrinolytic Therapy in Acute
Myocardial Infarction
DIDO
30 mins
Not PCI
capable
EMS Transport
PCI
capable
2013 STEMI
Guideline
PCI
Door-to-Balloon or FMC
to Balloon ≤ 120 mins
PCI + Thrombolytic Therapy
I IIa IIb III
B
2007 ACC/AHA
STEMI Guideline
• A planned strategy using full dose
fibrinolytic therapy followed by immediate
PCI is not recommended and may be
harmful.
Use of IIb/IIIa antagonists in STEMI
• Abciximab (Reopro)
• Eptifibatide (Integrilin)
• Tirofiban (Aggrastat)
IIb/IIIa Antagonists in STEMI
I IIa IIb III
B
2009 ACC/AHA
STEMI Guideline
Facilitated PCI
• The usefulness of IIb/IIIa receptor
antagonists (as part of a preparatory
pharmacologic strategy for STEMI patients
prior to arrival in cardiac catheterization
lab for angiography and PCI) is uncertain.
Use of Thienopyridines in STEMI
Also called P2Y12 receptor inhibitors
• Clopidogrel (Plavix)
• Prasugrel (Effient)
• Ticagrelor (Brilinta)
Use of Thienopyridines in STEMI
I IIa IIb III
C
• Clopidogrel during PCI
– 2007 STEMI guidelines 600 mg loading dose
– 2009 STEMI guidelines at least 300 to 600
mg
Prasugrel during PCI
– 2009 STEMI guidelines 60 mg loading dose
• Ticagrelor during PCI 180 mg loading dose
once followed by 90 mg bid. ASA 325 mg then
<100 mg maintenance dose
Use of Thienopyridines in STEMI
I IIa IIb III
C
• Clopidogrel with fibrinolytic therapy
– 2013 STEMI guidelines
• ≤ 75 y = 300 mg loading dose
• > 75 y = no loading dose
IIb/IIIa Antagonists in STEMI
I IIa IIb III
A
B
LOE:
2007 ACC/AHA A: Abciximab
STEMI Guideline B: Tirofiban
Integrilin
• It is reasonable to start treatment with
IIb/IIIa receptor antagonist at the time of
primary PCI (with or without stenting) in
selected patients with STEMI.
MKSAP Item #82
•
•
A 55 year old man is evaluated for a 2-month
history of dyspnea on exertion without chest
pain. Medical history is significant for type 2
diabetes mellitus, hypertension and
hyperlipidemia. Medications are metformin,
lisinopril, pravastatin and aspirin.
On physical exam, BP is 110/75 mm Hg and
pulse rate is 60/min. BMI is 35. Jugular venous
distention is noted, and trace lower extremity
edema is present.
MKSAP Item #82
• The point of maximal impulse is normal.
•
•
Cardiac exam reveals a regular rate and
rhythm and the chest is clear to
auscultation.
Laboratory studies show a serum B-type
naturetic peptide level of 110 pg/mL.
The EKG is shown. Echocardiogram
shows inferior wall hypokinesis and
ejection fraction of 35%.
MKSAP Item #82
MKSAP Item #82
• Which of the following is the most
appropriate diagnostic test to perform
next?
A.
B.
C.
D.
Adenosine thallium stress test
Cardiac magnetic resonance imaging
Cardiopulmonary exercise test
Coronary angiography
MKSAP Item #64
•
•
A 64-year old woman is evaluated in the ED for
chest pain and SOB. The chest pain began
earlier in the day after she received news that
her younger sister had died in a motor vehicle
accident. She reports no similar episodes of
chest pain before today. She takes no meds.
On PE, temperature is 37.30 C, BP is 150/80
mm Hg, pulse rate is 90/min, and respiration rate
is 11/min. BMI is 24. A normal carotid upstroke
without carotid bruits is noted, jugular venous
pulsations are normal, and normal S1 and S2 are
heard without murmurs.
MKSAP Item #64
•
•
Serum troponin level is 1.4 ng/mL.
EKG displays sinus rhythm at 90/min, 1-mm ST
elevation in leads V1 through V4, and no Q
waves. Echo shows reduced wall motion of the
anterior and apical portion of the heart,
hyperdynamic wall motion of the basal
segments, no significant valvular disease, and
no pericardial effusion. She undergoes
emergent coronary angiography, which shows
normal coronary arteries. Ventriculography
shows no movement of the apical portion of the
heart and hyperdynamic wall motion of the basal
segments of the heart.
MKSAP Item #64
• Which of the following is the most likely
diagnosis?
A.
B.
C.
D.
Non-ST elevation MI
Pericarditis
ST elevation MI
Stress cardiomyopathy
Item 68
•
•
A 56-year old man is admitted to the
hospital with new onset substernal chest
pressure. Medical history is remarkable for
hyperlipidemia. He is a cigarette smoker.
His medications are aspirin and
atorvastatin; upon admission to the
hospital, he began receiving metoprolol,
clopidogrel and IV heparin.
On PE, the patient is afebrile, BP is 132/78
mm HG, pulse rate is 82/min and regular,
and respiration rate is 14/min. No jugular
venous distention is note, the lungs are
clear to auscultation, no murmur or gallop
is heard and no peripheral edema is noted.
Item 68 (con’t)
•
On admission, cardiac troponin I level was
1.2 ng/mL; on hospital day 2, it peaks at 8.4
ng/mL. ECG on arrival to the ED
demonstrated nonspecific ST-T wave
abnormality, but no ST segment elevation
or depression. Cardiac catheterization
demonstrates overall preserved LV systolic
function with diffuse severe disease of the
distal portion of all three major epicardial
vessels. No catheterization based
intervention is performed.
Item 68 (con’t)
•
Which of the following is the most
appropriate management of this
patient’s clopidogrel therapy?
(A)
(B)
(C)
(D)
Stop clopidogrel
Continue clopidogrel for 2 weeks
Continue clopidogrel therapy for 1 year
Continue clopidogrel therapy lifelong.
Hospitalizations in the US due to ACS
Acute Coronary Syndromes
1.57 Million Hospital Admissions
79%
UA/NSTEMI
21%
STEMI
0.33 million admissions
1.24 million admissions
0.57 million NSTEMI
Heart Disease and Stroke Statistics 2007 Update
Circulation 2007;115:69-171
0.67 million UA
ACC/AHA 2009 Joint STEMI/PCI
Guidelines Focused Update
Acute Coronary Syndromes
Pathophysiology
Large
Fissure
Lipid Pool
Occlusive thrombus
(ST Elevation MI)
Macrophages
Stress, tensile,
internal
Shear forces,
external
Atherosclerotic
plaque
Small
Fissure
Fissure
Plaque
rupture
Mural thrombus
(unstable angina/
non-ST elevation MI)
Thrombus
Fuster V et al. NEJM. 1992; 326: 310-318.
Davies MJ et al. Circulation. 1990; 82 (Suppl II): II-38, II-46.
Myocardial Ischemia
Blood Supply
TIMI 1 or 2 Flow
Oxygen Demand
Heart Rate
Blood Pressure
Inotropicity
Non-ST elevation - coronary artery is not
completely occluded
Mortality Rates According to
Level of Cardiac Troponin
Mortality at 42 days
(Percentage of Patients)
8
7
Troponin Levels Predict Risk of Mortality
in ACS at 42 days in TIMI III B
7.5
6.0
6
5
4
3.4
3.7
3
2
1
1.7
1.0
831
0-0.4
174
148
0.4-<1.0 1.0 -<2.0
Circulation 2011;123:e451
NEJM 1996;335:1342-9
134
50
2.0 -<5.0 5.0 -<9
Cardiac Troponin (ng/ml)
67
>9.0
Non-ST Elevation MI/Unstable Angina
Non-ST Elevation MI/Unstable Angina
Diagnostic and Therapeutic Pathways
in Patients With and Without
Persistent ST-Segment Elevation
Acute Coronary Syndrome
ECG
Persistent
ST-segment elevation
ACS, No ST-segment
elevation
Thrombolysis, PCI
Aspirin, clopidogrel,
UFH or LMWH,
b-blockers, nitrates
Hamm CW et al. Lancet. 2001;358:1533-1538.
2002 ACC/AHA UA/NSTEMI Guideline Update. Available at: www.acc.org
Myocardial Ischemia
Blood Supply
TIMI 1 or 2 Flow
Oxygen Demand
Heart Rate
Blood Pressure
Inotropicity
Non-ST elevation ACS indicates that there is
coronary blood flow, but not adequate to
supply enough oxygen to the myocardium
Diagnostic and Therapeutic Pathways
in Patients With non-ST Segment Elevation
UA/NSTEMI
ASA/Clopidogrel/Heparin
Aggressive Therapy
Nitrates/Beta blockers
Conservative Therapy
Low risk
High risk
Coronary angiography
within 24-48 hours
Medical Therapy Only
Stress Test
Coronary angiography only if
Continuing ischemia or (+) Stress test
2007 ACC/AHA Guidelines for the Management of Patients with
Unstable angina/NSTEMI. www.acc.org
NSTEMI/Unstable Angina
• High Risk Markers (Invasive Strategy)
–
–
–
–
–
–
–
–
–
–
–
Elevated troponins
Recurrent angina/ischemia at rest or with low level activities
New or presumably new ST segment depression
Recurrent angina/ischemia with CHF, S3 gallop, rales, MR
High risk findings on noninvasive stress testing
Depressed LVF (EF <0.40)
Hemodynamic instability
Sustained VT
PCI within 6 months
Prior CABG
High GRACE or TIMI Risk Score
• Low Risk (Conservative Strategy)
2011 ACCF/AHA UA/Non-STEMI Guidelines. Circulation 2011;123 e458
TIMI Risk Score NSTEMI/Unstable Angina
•
•
•
•
•
•
•
7 Variables (One Point Each)
Age 65 years or older
At least 3 risk factors for CAD
Prior coronary stenosis of 50% or more
ST segment deviation on ECG presentation
At least 2 anginal events in prior 24 hours
Use of aspirin in prior 7 days
Elevated serum cardiac biomarkers
JAMA 2000;284:835-842
TIMI Risk Score
TIMI Risk Score
All Cause Mortality, New or Recurrent MI
or Severe Recurrent Ischemia Requiring
Urgent Revascularization Through 14
days after Randomization (%)
0-1
4.7%
2
8.3%
3
13.2%
4
19.9%
5
26.2%
6-7
40.9%
JAMA 2000;284:835-842
GRACE Prediction Score Card
•
•
•
Medical History
1.
2.
3.
Age in years (0-100 points)
History of congestive heart failure (24 points)
History of myocardial infarction (12 points)
Findings at initial hospital presentation
4.
5.
6.
Resting heart rate (0-43 points)
Systolic blood pressure (0-24 points)
ST depression (11 points)
Findings during hospitalization
7.
8.
9.
Initial serum creatinine (1 to 20 points)
Elevated cardiac enzymes (15 points)
No in-hospital percutaneous coronary intervention (14 points)
JAMA 2004:291;2727-33
Medical History
1.
Age in years
≤29
30-39
0
0
40-49
18
50-59
60-69
70-75
36
55
73
91
80-89
≥90
2.
3.
Points
History of CHF
History of MI
100
24
12
JAMA 2004:291;2727-33
Findings at Initial Hospital Presentation
4. Resting HR BPM
≤49.9
50-69.9
70-89.9
90-109.9
110-149.9
150-199.9
≥200
5. Systolic BP (mm Hg)
≤79.9
80-99.9
100-119.9
120-139.9
140-159.9
160-199.9
≥200
6. ST Segment Depression
Points
0
3
9
14
23
35
43
43
22
18
14
10
4
4
11
Findings During Hospitalization
7. Initial Serum Creatinine
0-0.39
0.4-0.79
0.8-1.19
1.2-1.59
1.6-1.99
2.3 -3.99
≥4
Points
1
3
5
7
9
15
20
8. Elevated Cardiac Enzyme
15
9. No In-hospital PCI
14
JAMA 2004:291;2727-33
Points
GRACE Prediction Score Card
JAMA 2004:291;2727-33
2. _______
3. _______
4. _______
5. _______
6. _______
7. _______
8. _______
9. _______
Total Score _____
Mortality Risk from
Plot __________
Probability (All Cause Mortality 6 Mos)
1. _______
0.50
0.40
0.30
Mortality Risk
0.20
0.10
0
70
90
110
130
150
170
190
210
Total Risk Score = No. of Points
NSTEMI/Unstable Angina
• High Risk Markers (Invasive Strategy)
–
–
–
–
–
–
–
–
–
–
–
Elevated troponins
Recurrent angina/ischemia at rest or with low level activities
New or presumably new ST segment depression
Recurrent angina/ischemia with CHF, S3 gallop, rales, MR
High risk findings on noninvasive stress testing
Depressed LVF (EF <0.40)
Hemodynamic instability
Sustained VT
PCI within 6 months
Prior CABG
High GRACE or TIMI Risk Score
• Low Risk (Conservative Strategy)
2011 ACCF/AHA UA/Non-STEMI Guidelines. Circulation 2011;123 e458
STRIVE
TM
Invasive Strategy for UA/NSTEMI
UA/NSTEMI
ASA (If ASA intolerant
Clopidogrel)
Invasive Strategy
Anticoagulant therapy (Enoxaparin or UFH
Bivaluridin or Fondaparinux)
Prior to Angiography
Initiate one or both of the following
Clopidogrel /IV IIb/IIIa inhibitor
Give both if there is Delay to Angiography, High Risk
Features, Early recurrent ischemic discomfort
Conservative Strategy for UA/NSTEMI
UA/NSTEMI
ASA (If ASA intolerant
Clopidogrel)
Conservative Strategy
Anticoagulant therapy (Enoxaparin or UFH or Fondaparinux but
enoxaparin and fondaparinus are preferable)
Initiate Clopidogrel
Consider adding IV eptifibatide or tirofiban
May need angio if LVEF <40%,
+ Stress test or there is Ischemia
(Induced or Spontaneous)
Continue ASA indefinitely Continue
clopidogrel >1 year
D/C IIb/IIIA if
started
D/C
anticoagulant therapy
Acute Coronary Syndrome
Non-ST Segment Elevation
• Aspirin
• Clopidogrel
• Heparin
• 2B/3A Antagonists
• Nitrates/Oxygen/Morphine
• Beta Blockers
• ACE Inhibitors/ARB’s
• Statins
• Aldosterone antagonist (EF <40%)
Medication/Intervention
Aspirin
Clopidogrel
Heparin
tPa (thrombolytic agent)
IIb/IIIa antagonists
Beta Blockers
ACE Inhibitors/ARB
Aldosterone Antagonists
Statins
STEMI
Non-STEMI/
Unstable
Angina
Yes
Yes
Yes
Yes
Yes
10 PCI – No
No PCI – Yes
Yes
10 PCI – Yes
No PCI – No
Yes
PCI – Yes
No
No PCI – High Risk
only -Yes
Yes
Yes
Yes
Yes
Yes
LV
Dysfunction
Yes
Yes