Acute Coronary Syndrome #2

July 26, 2013

Class of Recommendation

Class I: Benefit >>> Risk

Class IIa: Benefit >> Risk

Class IIb: Benefit ≥ Risk

Class III: Risk ≥ Benefit

Level of Evidence

AData from randomized clinical trials or meta-

analysis

Data from single randomized trial or

nonrandomized studies

B

CConsensus of opinion

of experts, case studies or standard of care

It is reasonable to perform procedure or treatment

It is reasonable to consider procedure or treatment

Procedure or treatment should not be performed

Procedure or treatment should be performed

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:

PCIcapable

Fibrinolysis Door-to-Needle or

FMC to Needle

< 30 mins

Coronary Angioplasty VS Fibrinolytic Therapy in Acute Myocardial Infarction

EMS Transport

Primary PCI Door-to-Balloon or FMC

to Balloon ≤ 90 mins

Not PCIcapable

PCIcapable

Not PCIcapable

Coronary Angioplasty VS Fibrinolytic Therapy in Acute Myocardial Infarction

EMS Transport

2013 STEMI Guideline

PCI Door-to-Balloon or FMC to Balloon ≤ 120 mins

DIDO30 mins

PCI + Thrombolytic Therapy

• A planned strategy using full dose fibrinolytic therapy followed by immediate PCI is not recommended and may be harmful.

I

BIIa IIb III

2007 ACC/AHA STEMI Guideline

Use of IIb/IIIa antagonists in STEMI

• Abciximab (Reopro)

• Eptifibatide (Integrilin)

• Tirofiban (Aggrastat)

IIb/IIIa Antagonists in STEMI

• 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.

I

BIIa IIb III

2009 ACC/AHA STEMI Guideline

Facilitated PCI

Use of Thienopyridines in STEMI

• Clopidogrel (Plavix)

• Prasugrel (Effient)

• Ticagrelor (Brilinta)

Also called P2Y12 receptor inhibitors

• 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

I

CIIa IIb III

Use of Thienopyridines in STEMI

• Ticagrelor during PCI 180 mg loading dose once followed by 90 mg bid. ASA 325 mg then <100 mg maintenance dose

• Clopidogrel with fibrinolytic therapy–2013 STEMI guidelines

• ≤ 75 y = 300 mg loading dose

• > 75 y = no loading dose

I

CIIa IIb III

Use of Thienopyridines in STEMI

• 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.

IAB

IIa IIb III2007 ACC/AHA

STEMI Guideline

LOE: A: AbciximabB: Tirofiban

Integrilin

IIb/IIIa Antagonists in 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. Adenosine thallium stress test

B. Cardiac magnetic resonance imaging

C. Cardiopulmonary exercise test

D. 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. Non-ST elevation MI

B. Pericarditis

C. ST elevation MI

D. 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) Stop clopidogrel

(B) Continue clopidogrel for 2 weeks

(C) Continue clopidogrel therapy for 1 year

(D) Continue clopidogrel therapy lifelong.

Hospitalizations in the US due to ACS

Acute Coronary Syndromes

1.57 Million Hospital Admissions

0.33 million admissions 1.24 million admissions

Heart Disease and Stroke Statistics 2007 UpdateCirculation 2007;115:69-171

0.67 million UA0.57 million NSTEMI

79%21%STEMI UA/NSTEMI

ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update

Pathophysiology

Fuster V et al. NEJM. 1992; 326: 310-318.Davies MJ et al. Circulation. 1990; 82 (Suppl II): II-38, II-46.

Lipid Lipid Pool

MacrophagesMacrophages

Stress, tensile,Stress, tensile,internalinternal

Shear forces,Shear forces,externalexternal

Atheroscleroticplaque

Fissure

Plaquerupture

LargeLargeFissureFissure

SmallSmallFissureFissure

Mural thrombusMural thrombus(unstable angina/(unstable angina/non-ST elevation MI)non-ST elevation MI)

Occlusive thrombusOcclusive thrombus(ST Elevation MI)(ST Elevation MI)

Thrombus

Acute Coronary Syndromes

Myocardial Ischemia

Heart Rate

Oxygen Demand Blood Supply

Blood Pressure Inotropicity

Non-ST elevation - coronary artery is not completely occluded

TIMI 1 or 2 Flow

Mortality Rates According to Level of Cardiac Troponin

0-0.4 0.4-<1.0

1.01.7

3.4

1.0 -<2.0 2.0 -<5.0

3.7

2

5

5.0 -<9

6.0

>9.0

7.5

Mo

rta

lity

at 4

2 d

ays

(P

erc

en

tag

e o

f Pa

tien

ts)

Cardiac Troponin (ng/ml)

1

3

4

6

7

8 Troponin Levels Predict Risk of Mortality in ACS at 42 days in TIMI III B

831 174 148 134 50 67

Circulation 2011;123:e451NEJM 1996;335:1342-9

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

Hamm CW et al. Lancet. 2001;358:1533-1538.2002 ACC/AHA UA/NSTEMI Guideline Update. Available at: www.acc.org

Acute Coronary Syndrome

ECG

Persistent ST-segment elevation

Thrombolysis, PCI Aspirin, clopidogrel,UFH or LMWH,

-blockers, nitrates

ACS, No ST-segment elevation

Myocardial Ischemia

Heart Rate

Oxygen Demand Blood Supply

Blood Pressure Inotropicity

Non-ST elevation ACS indicates that there is coronary blood flow, but not adequate to

supply enough oxygen to the myocardium

TIMI 1 or 2 Flow

2007 ACC/AHA Guidelines for the Management of Patients with Unstable angina/NSTEMI. www.acc.org

Diagnostic and Therapeutic Pathways in Patients With non-ST Segment Elevation

UA/NSTEMI

High risk

Coronary angiography within 24-48 hours

Low risk

Conservative Therapy

Coronary angiography only ifContinuing ischemia or (+) Stress test

Medical Therapy Only Stress Test

Aggressive Therapy

ASA/Clopidogrel/Heparin Nitrates/Beta blockers

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

2

3

4

5

6-7

4.7%

8.3%

13.2%

19.9%

26.2%

40.9%

JAMA 2000;284:835-842

GRACE Prediction Score Card

• Medical History1. Age in years (0-100 points)2. History of congestive heart failure (24 points)3. History of myocardial infarction (12 points)

• Findings at initial hospital presentation4. Resting heart rate (0-43 points)5. Systolic blood pressure (0-24 points)6. ST depression (11 points)

• Findings during hospitalization7. Initial serum creatinine (1 to 20 points)8. Elevated cardiac enzymes (15 points)9. No in-hospital percutaneous coronary intervention (14 points)

JAMA 2004:291;2727-33

1. Age in years Points

2. History of CHF 243. History of MI 12

Medical History

≤29

30-39

40-49

50-59

60-69

70-75

80-89

≥90

0

0

18

36

55

73

91

100

JAMA 2004:291;2727-33

Findings at Initial Hospital Presentation

4. Resting HR BPM Points

≤49.9 0

50-69.9 3

70-89.9 990-109.9 14

110-149.9 23

150-199.9 35

≥200 43

5. Systolic BP (mm Hg)≤79.9 43

80-99.9 22100-119.9 18120-139.9140-159.9

1410

160-199.9 4≥200 4

6. ST Segment Depression 11

Findings During Hospitalization

7. Initial Serum Creatinine Points

0-0.39 1

0.4-0.79 3

0.8-1.19 51.2-1.59 7

1.6-1.99 9

2.3 -3.99 15

≥4 20

8. Elevated Cardiac Enzyme 15

9. No In-hospital PCI 14

JAMA 2004:291;2727-33

GRACE Prediction Score Card

Pro

bab

ility

(A

ll C

aus

e M

ort

alit

y 6

Mo

s)

0

0.20

0.30

0.40

0.50

Total Risk Score = No. of Points

0.10

90 110 130 150 170 190 21070

JAMA 2004:291;2727-33

Mortality Risk

Points

1. _______

2. _______

3. _______

4. _______

5. _______

6. _______

7. _______

8. _______

9. _______

Total Score _____

Mortality Risk from Plot __________

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

STRIVETM

Invasive Strategy for UA/NSTEMIUA/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 SyndromeNon-ST Segment Elevation

• Aspirin

• Clopidogrel

• Heparin

• 2B/3A Antagonists

• Nitrates/Oxygen/Morphine

• Beta Blockers

• ACE Inhibitors/ARB’s

• Statins

• Aldosterone antagonist (EF <40%)

STEMIAspirin Yes

Non-STEMI/ Unstable Angina

Yes

Clopidogrel Yes Yes

Heparin Yes

IIb/IIIa antagonists

Yes10 PCI – No

tPa (thrombolytic agent) No

Beta Blockers Yes Yes

Yes YesACE Inhibitors/ARB

Aldosterone Antagonists Yes YesLV

Dysfunction

Statins Yes Yes

PCI – Yes 10 PCI – Yes

Medication/Intervention

No PCI – Yes

No PCI – No No PCI – High Risk only -Yes