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Page 1: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”
Page 2: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Acute Coronary Acute Coronary SyndromeSyndrome

Dr. S.A. moezziDr. S.A. moezzi

Page 3: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

ACS OverviewACS Overview

Overview of ACSOverview of ACS Assessment of “Likelihood of ACS”Assessment of “Likelihood of ACS” Early Risk StratificationEarly Risk Stratification Invasive vs Conservative StrategyInvasive vs Conservative Strategy PharmacotherapyPharmacotherapy Long-term Therapy/Secondary PreventionLong-term Therapy/Secondary Prevention

Page 4: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Scope of the ProblemScope of the Problem

5 million ER visits nationwide for CP5 million ER visits nationwide for CP 800,000 experience an MI each year800,000 experience an MI each year

213,000 die from their event213,000 die from their event ½ of those die before reaching the ER½ of those die before reaching the ER

Pre-CCU, mortality for MI was >30%Pre-CCU, mortality for MI was >30% Fell to 15% with CCUFell to 15% with CCU

With current interventions, in hospital mortality of With current interventions, in hospital mortality of STEMI is 6-7%STEMI is 6-7%

Page 5: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Overview of ACS

Acute Coronary Syndromes*

1.57 Million Hospital Admissions - ACS

UA/NSTEMI† STEMI

1.24 million Admissions per year

0.33 million 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.

Page 6: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Acute Coronary Syndrome (ACS)Acute Coronary Syndrome (ACS)

Definition:Definition: The spectrum of acute ischemia The spectrum of acute ischemia related syndromes ranging from UA to MI related syndromes ranging from UA to MI with or without ST elevation with or without ST elevation that are that are secondary to acute plaque rupture or plaque secondary to acute plaque rupture or plaque erosion.erosion.

[----[----UAUA------------------NSTEMINSTEMI--------------------STEMISTEMI----]----]

Page 7: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Decreased O2 Supply

•Flow- limiting stenosis

•Anemia

•Plaque rupture/clot

Increased O2 Demand

O2 supply/demand mismatch→Ischemia

Myocardial ischemia→necrosis

Pathophysiology ACS

Asy

mpt

omat

ic

Ang

ina

Myo

card

ial I

nfar

ctio

n

Pathophysiology of Stable Angina and ACSPathophysiology of Stable Angina and ACS

Page 8: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Pathophysiology of ACSPathophysiology of ACSEvolution of Coronary ThrombosisEvolution of Coronary Thrombosis

Page 9: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Unstable Unstable AnginaAngina STEMISTEMI NSTEMINSTEMI

Non occlusive thrombus

Non specific ECG

Normal cardiac enzymes

Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis

ST depression +/- T wave inversion on ECG

Elevated cardiac enzymes

Complete thrombus occlusion

ST elevations on ECG or new LBBB

Elevated cardiac enzymes

More severe symptoms

Page 10: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

STEMISTEMI

Name 3 situations in which you cannot Name 3 situations in which you cannot diagnose STEMIdiagnose STEMI

Page 11: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

STEMISTEMI

Name 3 situations in which you cannot Name 3 situations in which you cannot diagnose STEMIdiagnose STEMI

Left Ventricular HypertrophyLeft Ventricular Hypertrophy Chronic or Rate Dependent LBBBChronic or Rate Dependent LBBB Paced RhythmPaced Rhythm

Page 12: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Diagnosis of ACSDiagnosis of ACS

At least 2 of the At least 2 of the followingfollowing History ( angina or angina History ( angina or angina

equivalent)equivalent) Acute ischemic ECG changesAcute ischemic ECG changes Typical rise and fall of cardiac Typical rise and fall of cardiac

markersmarkers Absence of another identifiable Absence of another identifiable

etiologyetiology

Page 13: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Likelihood of ACS by Hx/PELikelihood of ACS by Hx/PE

History/ExaminationHistory/Examination Pain in Chest or Left ArmPain in Chest or Left Arm CP RadiationCP Radiation

Right ShoulderRight Shoulder Left ArmLeft Arm Both Left & Right ArmBoth Left & Right Arm

DiaphoresisDiaphoresis 33rdrd Heart Sound Heart Sound SBP < 80 mm HgSBP < 80 mm Hg Pulmonary Crackles Pulmonary Crackles

Panju AA. Panju AA. JAMA.JAMA. 1998;280:1256. 1998;280:1256.

Suggesting AMISuggesting AMILR 2.7LR 2.7

LR 2.9 (1.4-6.0)LR 2.9 (1.4-6.0)

LR 2.3 (1.7-3.1)LR 2.3 (1.7-3.1)

LR 7.1 (3.6-14.2)LR 7.1 (3.6-14.2)

LR 2.0 (1.9-2.2)LR 2.0 (1.9-2.2)

LR 3.2 (1.6-6.5)LR 3.2 (1.6-6.5)

LR 3.1 (1.8-5.2)LR 3.1 (1.8-5.2)

LR 2.1 (1.4-3.1)LR 2.1 (1.4-3.1)

Page 14: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Likelihood of ACS by Hx/PELikelihood of ACS by Hx/PE

Clinical Examination – Clinical Examination – Pleuritic Chest PainPleuritic Chest Pain Sharp or Stabbing PainSharp or Stabbing Pain Positional Chest PainPositional Chest Pain Reproducible Chest PainReproducible Chest Pain

Panju AA. Panju AA. JAMA.JAMA. 1998;280:1256. 1998;280:1256.

Against AMIAgainst AMI

LR 0.2 (0.2-0.3)LR 0.2 (0.2-0.3)

LR 0.3 (0.2-0.5)LR 0.3 (0.2-0.5)

LR 0.3 (0.2-0.4)LR 0.3 (0.2-0.4)

LR 0.2-0.4LR 0.2-0.4

Page 15: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”
Page 16: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Risk Stratification by ECGRisk Stratification by ECG

Simple, quick, noninvasive toolSimple, quick, noninvasive tool Universally available, cheapUniversally available, cheap Correlates with risk and prognosisCorrelates with risk and prognosis Guides treatment decisionsGuides treatment decisions Can identify alternative causes Can identify alternative causes

Page 17: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Risk Stratification by ECGRisk Stratification by ECG

ECG Findings and Associated LR for AMIECG Findings and Associated LR for AMI New ST-E New ST-E >> 1mm 1mm LR 5.7-53.9LR 5.7-53.9 New Q wavesNew Q waves LR 5.3-24.8LR 5.3-24.8 Any ST-EAny ST-E LR 11.2 (7.1-17.8)LR 11.2 (7.1-17.8) New Conduction DefectNew Conduction Defect LR 6.3 ( 2.5-15.7)LR 6.3 ( 2.5-15.7) New ST-DNew ST-D LR 3.0-5.2LR 3.0-5.2

NORMAL ECGNORMAL ECG LR 0.1-0.4LR 0.1-0.4

Panju AA. Panju AA. JAMA.JAMA. 1998;280:1256. 1998;280:1256.

Page 18: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Risk Stratification by ECGRisk Stratification by ECG

1-8% AMI have a normal ECG1-8% AMI have a normal ECG

Only Approx 50%Only Approx 50% of AMI patients have of AMI patients have diagnostic changes on theirdiagnostic changes on their initial initial ECG ECG

Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.

Page 19: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Risk Stratification by ECGRisk Stratification by ECG

1 ECG cannot exclude AMI1 ECG cannot exclude AMI

Brief sample of a dynamic processBrief sample of a dynamic process

Small regions of ischemia or infarction may be Small regions of ischemia or infarction may be missedmissed

Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.

Page 20: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”
Page 21: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

How Sensitive is the ECG Alone?How Sensitive is the ECG Alone?

Page 22: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

How Predictive is NTG response?How Predictive is NTG response?

Page 23: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Timing of Release of Various Biomarkers After Timing of Release of Various Biomarkers After Acute Myocardial InfarctionAcute Myocardial Infarction

Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd 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.

Page 24: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

1.01.7

3.4 3.7

6.0

7.5

0

1

2

3

4

5

6

7

8

0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0 9.0

Cardiac troponin I (ng/ml)

Mo

rtal

ity

at 4

2 D

ays

831 174 148 134 50 67

%%

%%

%

%

Risk Stratification by TroponinRisk Stratification by Troponin

Page 25: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

National Academy of Clinical Biochemistry Laboratory Medicine National Academy of Clinical Biochemistry Laboratory Medicine ((NACBNACB) and the Joint ) and the Joint ESC/ACCF/AHA/WHF ESC/ACCF/AHA/WHF Task Force for the Task Force for the

Redefinition of Myocardial Infarction Redefinition of Myocardial Infarction

  • • Cardiac troponin is the Cardiac troponin is the preferred preferred marker for the diagnosis marker for the diagnosis of MI and for risk stratification. CK-MB by mass assay is an of MI and for risk stratification. CK-MB by mass assay is an

acceptable acceptable alternativealternative when troponin in not available. when troponin in not available.   • • CK-MB was preferred by the NACB for the detection of CK-MB was preferred by the NACB for the detection of

reinfarctionreinfarction early after the index eventearly after the index event increased increased sensitivity and specificity of cTn sensitivity and specificity of cTn should make it the should make it the

marker of choice it is unnecessary to obtain both values.marker of choice it is unnecessary to obtain both values. Cardiac troponins I and T are Cardiac troponins I and T are equally equally usefuluseful..

Page 26: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Non ACS causes of Troponin ElevationNon ACS causes of Troponin Elevation1.1. Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac

surgery, after-interventionalsurgery, after-interventional closure of ASDs)closure of ASDs)2.2. Congestive heart failure (acute and chronic)Congestive heart failure (acute and chronic)3.3. Aortic valve disease and HOCM with significant LVHAortic valve disease and HOCM with significant LVH4.4. HypertensionHypertension5.5. Hypotension, often with arrhythmiasHypotension, often with arrhythmias6.6. Noncardiac surgery Noncardiac surgery 7.7. Renal failureRenal failure8.8. Critically ill patients, especially with diabetes, respiratory failureCritically ill patients, especially with diabetes, respiratory failure9.9. Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms)Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms)10.10. HypothyroidismHypothyroidism11.11. Coronary vasospasm, including apical ballooning syndromeCoronary vasospasm, including apical ballooning syndrome12.12. Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, 13.13. Post-PCI Post-PCI 14.14. Pulmonary embolism, severe pulmonary hypertensionPulmonary embolism, severe pulmonary hypertension15.15. SepsisSepsis16.16. Burns, especially if TBSA greater than 30%Burns, especially if TBSA greater than 30%17.17. Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and sclerodermaInfiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma18.18. Acute neurologic disease, including CVA, subarchnoid bleedsAcute neurologic disease, including CVA, subarchnoid bleeds19.19. Rhabdomyolysis with cardiac injuryRhabdomyolysis with cardiac injury20.20. Transplant vasculopathyTransplant vasculopathy21.21. Vital exhaustionVital exhaustion

Modified from Apple FS, et al Heart J. 2002;144:981-986.

Page 27: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Combined Sensitivities for ACSCombined Sensitivities for ACS

Page 28: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Unstable angina/NSTEMI cardiac Unstable angina/NSTEMI cardiac carecare

Evaluate for Evaluate for conservative vs. invasiveconservative vs. invasive strategy strategy based upon:based upon:

Likelihood of actual ACSLikelihood of actual ACS Risk stratification by Risk stratification by TIMI risk scoreTIMI risk score ACS risk categories per AHA guidelinesACS risk categories per AHA guidelines

LowLowIntermediateIntermediate

HighHigh

Page 29: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

TIMI Risk Score

Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days

Page 30: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

TIMI Risk ScoreTIMI 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 leadsA2:Aspirin use within the past 7 days; Age over 65T: Two or more episodes of CP within 24 hours

Page 31: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Deciding between Early Invasive vs a Conservative StrategiesDeciding between Early Invasive vs a Conservative Strategies

Definitive/Possible ACSDefinitive/Possible ACSInitiate ASA, BB, Nitrates, Initiate ASA, BB, Nitrates, Anticoagulants, TelemetryAnticoagulants, Telemetry

Early Invasive StrategyEarly Invasive Strategy

• TIMI Risk Score TIMI Risk Score >>33• New ST segment New ST segment deviationdeviation• Positive biomarkersPositive biomarkers

Conservative StrategyConservative Strategy

•TIMI Risk Score <3 (Esp. Women)TIMI Risk Score <3 (Esp. Women)•No ST segment deviationNo ST segment deviation•Negative BiomarkersNegative Biomarkers

Coronary angiographyCoronary angiography(24-48 hours)(24-48 hours)

Recurrent Signs/SymptomsRecurrent Signs/SymptomsHeart failureHeart failureArrhythmiasArrhythmias

Remains StableRemains Stable↓↓

Assess EF and/or Stress TestingAssess EF and/or Stress Testing↓↓

EF<40% OR Positive stressEF<40% OR Positive stressGo to AngiographyGo to Angiography

•Hemodynamic instabilityHemodynamic instability•Elecrical instabilityElecrical instability•Refractory anginaRefractory angina•PCI in past 6 monthsPCI in past 6 months•CABGCABG•EF <40%EF <40%

Page 32: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”
Page 33: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Specifics of Early Hospital CareSpecifics of Early Hospital Care

Anti-Ischemic TherapyAnti-Ischemic TherapyAnti-Platelet TherapyAnti-Platelet TherapyAnticoagulant TherapyAnticoagulant Therapy

Page 34: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Early Hospital CareEarly Hospital CareAnti-Ischemic TherapyAnti-Ischemic Therapy

Class IClass I Bed/Chair rest and TelemetryBed/Chair rest and Telemetry OxygenOxygen (maintain saturation >90%) (maintain saturation >90%) NitratesNitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart (SLx3 Oral/topical. IV for ongoing iscemia, heart

failure, hypertension)failure, hypertension) Oral Oral BB-blockers-blockers in First 24-hours if no contraindications. in First 24-hours if no contraindications.

(IV (IV BB-blockers class IIa indication)-blockers class IIa indication) Non-dihydropyridine Non-dihydropyridine Ca-channel blockersCa-channel blockers for those with for those with

contraindication fo B-blockerscontraindication fo B-blockers ACE inhibitorsACE inhibitors in first 24-hours for heart failure or in first 24-hours for heart failure or

EF<40% (Class IIa for all other pts) (EF<40% (Class IIa for all other pts) (ARBsARBs for those for those intolerant)intolerant)

StatinsStatins

Page 35: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Early Hospital CareEarly Hospital CareAnti-Ischemic TherapyAnti-Ischemic Therapy

Class IIIClass III Nitrates if Nitrates if BP<90 mmHg or RV infarctionBP<90 mmHg or RV infarction Nitrates within 24-hrs of Nitrates within 24-hrs of SildenafilSildenafil or 48 hrs of or 48 hrs of TadalafilTadalafil Immediate release dihydropyradine Ca-blockersImmediate release dihydropyradine Ca-blockers in the in the

absence of B-Blocker therapyabsence of B-Blocker therapy IV ACE-inhibitorsIV ACE-inhibitors IV IV BB-blockers-blockers in patients with acute HF, Low output state in patients with acute HF, Low output state

or cardiogenic shock, PR interval >0.24 sec, 2or cardiogenic shock, PR interval >0.24 sec, 2ndnd or 3 or 3rdrd degree heart block, active asthma, or reactive airway degree heart block, active asthma, or reactive airway diseasedisease

NSAIDS and Cox-2 inhibitorsNSAIDS and Cox-2 inhibitors

Page 36: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Early Hospital CareEarly Hospital CareAnti-Platelet TherapyAnti-Platelet Therapy

Class IClass I AspirinAspirin (162-325 mg), non enteric coated (162-325 mg), non enteric coated ClopidogrelClopidogrel for those with Aspirin for those with Aspirin

allergy/intolerance (300-600 mg load and 75 mg/d)allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleedGI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitorsGP IIb/IIIa inhibitors should be evaluated based on should be evaluated based on

whether an invasive or conservative strategy is usedwhether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all GP IIb/IIIa inhibitors recommended for all diabeticsdiabetics

and all patient in early invasive armand all patient in early invasive arm

Page 37: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

secondary preventionsecondary prevention

At present, the United States Food and Drug At present, the United States Food and Drug Administration recommends daily doses Administration recommends daily doses of 75 of 75 to 325 mgto 325 mg, ,

the 2006 American College of Cardiology the 2006 American College of Cardiology /American Heart Association (ACC/AHA) /American Heart Association (ACC/AHA) guidelines on recommends daily doses of guidelines on recommends daily doses of 75 to 75 to 162 mg 162 mg for secondary prevention [38]. for secondary prevention [38].

The ACCP recommends a daily dose of The ACCP recommends a daily dose of 75 to 75 to 100 mg100 mg

Page 38: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Early Hospital CareEarly Hospital CareAnticoagulant TherapyAnticoagulant Therapy

Class IClass I Unfractionated HeparinUnfractionated Heparin EnoxaparinEnoxaparin BivalarudinBivalarudin FondaparinuxFondaparinux

Relative choice depends on invasive vs Relative choice depends on invasive vs conservative strategy and bleeding riskconservative strategy and bleeding risk

Page 39: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Early Hospital CareEarly Hospital CareStatin TherapyStatin Therapy

MIRACL TrialMIRACL TrialInclusion CriteriaInclusion Criteria 3086 patients with Non ST ACS3086 patients with Non ST ACS Total cholesterol <270 mg/dlTotal cholesterol <270 mg/dl No planned PCINo planned PCI Randomized to Randomized to Atorvastatin vs PlaceboAtorvastatin vs Placebo Drug started at 24-96 hoursDrug started at 24-96 hours

Page 40: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Statin Evidence: MIRACL StudyStatin Evidence: MIRACL Study

Relative risk = 0.84P = .04895% CI 0.701-0.999

Atorvastatin

Placebo

0

5

10

15

0 4 8 12 16

Time Since Randomization (weeks)

Cu

mu

lati

ve In

cid

ence

(%

)

Time to first occurrence of:• Death (any cause)• Nonfatal MI• Resuscitated cardiac arrest• Worsening angina with new

objective evidence and urgent rehospitalization

17.4%

14.8%

Primary Efficacy Measure

Schwartz GG, et al. JAMA. 2001;285:1711-1718.

Page 41: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Statin Evidence: MIRACL StudyStatin Evidence: MIRACL Study

0

0.5

1

1.5

2

0 4 8 12 16

Time Since Randomization (weeks)

Cu

mu

lati

ve In

cid

ence

(%

)

Relative risk = 0.49P = .0495% CI 0.24-0.98

Atorvastatin

Placebo

Fatal and Nonfatal Stroke

Waters DD, et al. Circulation. 2002;106:1690-1695. S24

Page 42: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

All-Cause Death or Major CV Events in All Randomized Subjects

00 33 1818 2121 2424 2727 303066 99 1212 1515

% with

Event

Months of Follow-up

Pravastatin 40mgPravastatin 40mg(26.3%)(26.3%)

Atorvastatin 80mgAtorvastatin 80mg(22.4%)(22.4%)

16% RR16% RR

(P = (P = 0.005)0.005)

3030

2525

2020

1515

1010

55

00

PROVE-IT TrialPROVE-IT Trial

Page 43: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Summary of PROVE-IT Results Summary of PROVE-IT Results

In patients recently hospitalized within 10 days for an In patients recently hospitalized within 10 days for an acute coronary syndrome: acute coronary syndrome:

““Intensive” high-dose LDL-C loweringIntensive” high-dose LDL-C lowering (median LDL-C 62 (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) therapy (median LDL-C 95 mg/dL) reduced the risk of all cause reduced the risk of all cause mortality or major cardiac events by 16%mortality or major cardiac events by 16% (p=0.005) (p=0.005)

BenefitsBenefits emerged emerged within 30 dayswithin 30 days post ACS with continued benefit post ACS with continued benefit observed throughout the observed throughout the 2.5 years of follow-up2.5 years of follow-up

Benefits were consistent across all cardiovascular endpoints, Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups except stroke, and most clinical subgroups

Page 44: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Invasive vs Conservative Invasive vs Conservative StrategiesStrategies

Page 45: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Invasive vs Conservative Strategy Invasive vs Conservative Strategy Clinical TrialsClinical Trials

TIMI IIIB (94)

ConservativeStrategy Favored

N=920

InvasiveStrategy Favored

N=7,018

VANQWISH (98)

MATE

FRISC II (99)

TACTICS-TIMI 18 (01)

VINO

RITA-3 (02)

TRUCS

ISAR-COOL

ICTUS (05)

No differenceNo differenceN=2,874N=2,874

Weight ofWeight ofthe evidencethe evidence

Page 46: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

How Early is Early?How Early is Early?

Page 47: Acute Coronary Syndrome Dr. S.A. moezzi ACS Overview Overview of ACS Overview of ACS Assessment of “Likelihood of ACS” Assessment of “Likelihood of ACS”

Secondary PreventionSecondary PreventionClass I IndicationsClass I Indications

AspirinAspirin Beta-blockers:Beta-blockers: (all pts, slow titration with moderate to (all pts, slow titration with moderate to

severe failuresevere failure ACE-Inhibitors: ACE-Inhibitors: CHF, EF<40%, HTN, DMCHF, EF<40%, HTN, DM (All pts-Class IIa) (All pts-Class IIa) ARBARB when intolerant to ACE. when intolerant to ACE.

(Class IIa as alternative to ACEI)(Class IIa as alternative to ACEI)Aldosterone blockade:Aldosterone blockade: An ACEI, CHF with either An ACEI, CHF with either

EF<40% or DM and if CrCl>30 ml/min and KEF<40% or DM and if CrCl>30 ml/min and K<<5.0 5.0 mEq/LmEq/L

StatinsStatins Standard Risk Factor ManagementStandard Risk Factor Management

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Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI

Medical Therapy without Stent

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)

Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B)

Continue with dual antiplatelet therapy as

above

Yes

No

Indication for Anticoagulation?

ASA 75 to 162 mg/d indefinitely (Class I,

LOE: A)

&

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)

Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence.

UA/NSTEMI Patient

Groups at Discharge

New

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Secondary PreventionSecondary PreventionClass IIIClass III

Hormone Replacement TherapyHormone Replacement Therapy Antioxidants (Vit C, Vit E)Antioxidants (Vit C, Vit E) Folic AcidFolic Acid

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Early Treatment with ClopidogrelEarly Treatment with Clopidogrel

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Shortcomings of the CURE TrialShortcomings of the CURE Trial

Conducted primarily at centers Conducted primarily at centers without routine without routine use of early invasive strategyuse of early invasive strategy

Only 462 Only 462 (3.7%)(3.7%) patients enrolled from the patients enrolled from the U.SU.S.. 44% had catheterization during index 44% had catheterization during index

hospitalizationhospitalization Adverse event reduced only in nonfatal MI setAdverse event reduced only in nonfatal MI set Major Bleeding rate of 9.6% among patients Major Bleeding rate of 9.6% among patients

who were administered clopidogrel within 5 who were administered clopidogrel within 5 days of CABGdays of CABG

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ClopidogrelClopidogrelBleeding Risk and CABGBleeding Risk and CABG

““In hospitals in which patients with In hospitals in which patients with UA/NSTEMI undergo rapid diagnostic UA/NSTEMI undergo rapid diagnostic catheterization within 24 hours of admission, catheterization within 24 hours of admission, clopidogrel is not started until it is clear that clopidogrel is not started until it is clear that CABG will not be scheduled within the next CABG will not be scheduled within the next several days. However, unstable patients several days. However, unstable patients should receive clopidogrel or be take for should receive clopidogrel or be take for immediate angiography.”immediate angiography.”

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Clopidogrel vs. PrasugrelClopidogrel vs. Prasugrel

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Prasugrel-Key FactsPrasugrel-Key Facts

ContraindicatedContraindicated in pts with in pts with prior TIA/Strokeprior TIA/Stroke Not recommended for patients Not recommended for patients >>75 years75 years 5 mg maintenance dose suggested in patients 5 mg maintenance dose suggested in patients

<60 Kg<60 Kg, though this dose has not been studied, though this dose has not been studied

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SummarySummary

ACS includes UA, NSTEMI, and STEMIACS includes UA, NSTEMI, and STEMI

Management guideline focusManagement guideline focus Immediate assessment/intervention Immediate assessment/intervention (MONA+BAH)(MONA+BAH) Risk stratification Risk stratification (UA/NSTEMI vs. STEMI)(UA/NSTEMI vs. STEMI) RAPID reperfusion for STEMI RAPID reperfusion for STEMI (PCI vs. Thrombolytics)(PCI vs. Thrombolytics) Conservative vs Invasive therapy for UA/NSTEMIConservative vs Invasive therapy for UA/NSTEMI

Aggressive attention to secondary prevention Aggressive attention to secondary prevention initiatives for ACS patients initiatives for ACS patients

Beta blocker, ASA, ACE-I, StatinBeta blocker, ASA, ACE-I, Statin

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Ten Points to Remember Ten Points to Remember from thefrom the

2009 STEMI Guideline Update 2009 STEMI Guideline Update

Antman EM, Hand M,Antman EM, Hand M,Armstrong PW, et al., Armstrong PW, et al.,

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1.1. Patients routinely taking NSAIDs (except for Patients routinely taking NSAIDs (except for aspirin), both nonselective as well as COX-2 aspirin), both nonselective as well as COX-2 selective agents, before STEMI should have selective agents, before STEMI should have those agents those agents discontinueddiscontinued at the time of at the time of presentation with STEMI because of the presentation with STEMI because of the increased risk of increased risk of mortalitymortality, , reinfarctionreinfarction, , hypertension, heart failure, and myocardial hypertension, heart failure, and myocardial rupturerupture associated with their use. associated with their use.

Ten Points to RememberTen Points to Remember from the from the

2009 STEMI Guideline Update2009 STEMI Guideline Update

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2.2. Oral beta-blocker therapy should be initiated in the Oral beta-blocker therapy should be initiated in the first 24 hours for patients who do first 24 hours for patients who do notnot have any of the have any of the following: following:

a)a) Signs of heart failure Signs of heart failure

b)b) Evidence of a low output state Evidence of a low output state

c)c) Increased risk for cardiogenic shock Increased risk for cardiogenic shock d)d) Other relative contraindications to beta blockadeOther relative contraindications to beta blockade

PR interval > 0.24 seconds PR interval > 0.24 seconds Second- or third-degree heart block Second- or third-degree heart block Active asthma or reactive airway disease Active asthma or reactive airway disease

Ten Points to RememberTen Points to Remember from the from the

2009 STEMI Guideline Update2009 STEMI Guideline Update

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3.3. STEMI patients presenting to a hospital with PCI STEMI patients presenting to a hospital with PCI capability should be treated with primary PCI within capability should be treated with primary PCI within 90 minutes of first medical contact as a systems goal.90 minutes of first medical contact as a systems goal.

4.4. STEMI patients presenting to a hospital without PCI STEMI patients presenting to a hospital without PCI capability and who cannot be transferred to a PCI capability and who cannot be transferred to a PCI center and undergo PCI within 90 minutes of first center and undergo PCI within 90 minutes of first medical contact should be treated with fibrinolytic medical contact should be treated with fibrinolytic therapy within 30 minutes of hospital presentation as therapy within 30 minutes of hospital presentation as a systems goal unless fibrinolytic therapy is a systems goal unless fibrinolytic therapy is contraindicated.contraindicated.

Ten Points to RememberTen Points to Remember from the from the

2009 STEMI Guideline Update2009 STEMI Guideline Update

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Ten Points to RememberTen Points to Remember from the from the

2009 STEMI Guideline Update2009 STEMI Guideline Update

5.5. A strategy of coronary angiography with intent to A strategy of coronary angiography with intent to perform PCI (or emergency CABG) is recommended perform PCI (or emergency CABG) is recommended for patients who have received fibrinolytic therapy for patients who have received fibrinolytic therapy and have any of the following: and have any of the following:

• Cardiogenic shock in patients <75 years who are suitable Cardiogenic shock in patients <75 years who are suitable candidates for revascularization, candidates for revascularization,

• Severe congestive heart failure and/or pulmonary edema Severe congestive heart failure and/or pulmonary edema (Killip class III), or(Killip class III), or

• Hemodynamically compromising ventricular arrhythmias Hemodynamically compromising ventricular arrhythmias

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Ten Points to RememberTen Points to Remember from the from the

2009 STEMI Guideline Update2009 STEMI Guideline Update

6.6. Patients undergoing reperfusion with fibrinolytics Patients undergoing reperfusion with fibrinolytics should receive anticoagulant therapy for a should receive anticoagulant therapy for a minimum of 48 hours and preferably for the minimum of 48 hours and preferably for the duration of the index hospitalization, up to 8 days duration of the index hospitalization, up to 8 days (regimens other than unfractionated heparin [UFH] (regimens other than unfractionated heparin [UFH] are recommended if anticoagulant therapy is given are recommended if anticoagulant therapy is given for more than 48 hours because of the risk of for more than 48 hours because of the risk of heparin- induced thrombocytopenia with prolonged heparin- induced thrombocytopenia with prolonged UFH treatment).UFH treatment).

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Ten Points to RememberTen Points to Remember from the from the

2009 STEMI Guideline Update2009 STEMI Guideline Update

7.7. Clopidogrel 75 mg per day orally should be added Clopidogrel 75 mg per day orally should be added to aspirin in patients with STEMI regardless of to aspirin in patients with STEMI regardless of whether they undergo reperfusion with whether they undergo reperfusion with fibrinolytic therapy or do not receive reperfusion fibrinolytic therapy or do not receive reperfusion therapy. Treatment with clopidogrel should therapy. Treatment with clopidogrel should continue for at least 14 days.continue for at least 14 days.

8.8. Every tobacco user and family members who Every tobacco user and family members who smoke should be advised to quit at every visit.smoke should be advised to quit at every visit.

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Ten Points to RememberTen Points to Remember from the from the

2007 STEMI Guideline Update2007 STEMI Guideline Update

9.9. For all post-PCI STEMI stented patients without For all post-PCI STEMI stented patients without aspirin resistance, allergy, or increased risk of aspirin resistance, allergy, or increased risk of bleeding, aspirin at a dose of 162-325 mg daily bleeding, aspirin at a dose of 162-325 mg daily should be given for at least 1 month after bare-should be given for at least 1 month after bare-metal stent (BMS) implantation, 3 months after metal stent (BMS) implantation, 3 months after sirolimus-eluting stent implantation, and 6 months sirolimus-eluting stent implantation, and 6 months after paclitaxel-eluting stent implantation, after after paclitaxel-eluting stent implantation, after which long-term aspirin use should be continued which long-term aspirin use should be continued indefinitely at a dose of 75-162 mg daily.indefinitely at a dose of 75-162 mg daily.

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Ten Points to RememberTen Points to Remember from the from the

2007 STEMI Guideline Update2007 STEMI Guideline Update

10.10. For all post-PCI patients who receive a drug-For all post-PCI patients who receive a drug-eluting stent, clopidogrel 75 mg daily should be eluting stent, clopidogrel 75 mg daily should be given for at least 12 months if patients are not at given for at least 12 months if patients are not at high risk of bleeding. For post-PCI patients high risk of bleeding. For post-PCI patients receiving a BMS, clopidogrel should be given for a receiving a BMS, clopidogrel should be given for a minimum of 1 month and ideally up to 12 months minimum of 1 month and ideally up to 12 months (unless the patient is at increased risk of bleeding; (unless the patient is at increased risk of bleeding; then it should be given for a minimum of 2 weeks). then it should be given for a minimum of 2 weeks).

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ACC/AHA Guideline Classification System ACC/AHA Guideline Classification System Level of Evidence (LOE)Level of Evidence (LOE)

LOE A – strong evidence Multiple large randomized trials

LOE B – Intermediate

Limited # or small trials Nonrandomized studies/observational registries

LOE C – Expert consensus/Opinion

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Beta-blockers in STEMIBeta-blockers in STEMI Class I - oral beta-blockers should be initiated within 24 Class I - oral beta-blockers should be initiated within 24

hourshours* * LOE BLOE B

Class IIa - reasonable to administer IV beta-blocker at the time Class IIa - reasonable to administer IV beta-blocker at the time of presentation who are hypertensiveof presentation who are hypertensive* * LOE BLOE B

Class III - IV beta-blockers should not be administered to Class III - IV beta-blockers should not be administered to patients with any of the followingpatients with any of the following* * LOE ALOE A

** Contraindications include Contraindications include 1)1) signs of heart failure, signs of heart failure, 2)2) evidence of low output state, evidence of low output state, 3)3) risk for cardiogenic shock (age>70, SBP<120, sinus tach>110bpm, HR<60, risk for cardiogenic shock (age>70, SBP<120, sinus tach>110bpm, HR<60, increased time since onset of STEMI), increased time since onset of STEMI), 4)4) or other relative contraindication or other relative contraindication (PR>0.24s, heart block, active asthma)(PR>0.24s, heart block, active asthma)

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UFH/ LMWH in STEMIUFH/ LMWH in STEMI Class I - Patients receiving fibrinolytics should receive Class I - Patients receiving fibrinolytics should receive

anticoagulant therapy for a minimum of 48 hrs, LOE C. anticoagulant therapy for a minimum of 48 hrs, LOE C. Because of heparin induced thrombocytopenia, regimens other Because of heparin induced thrombocytopenia, regimens other than UFH are recommended for patients receiving than UFH are recommended for patients receiving anticoagulant therapy > 48 hrs, LOE A.anticoagulant therapy > 48 hrs, LOE A.

DOSE:DOSE: UFH - 60 U/kg (max 4000 U) bolus, then 12 U/kg per hr dripUFH - 60 U/kg (max 4000 U) bolus, then 12 U/kg per hr drip Enoxaparin - (Cr <2.5 men, <2.0 women)Enoxaparin - (Cr <2.5 men, <2.0 women)

For pts age <75 give 30mg IV bolus followed 15min later by 1 mg/kg For pts age <75 give 30mg IV bolus followed 15min later by 1 mg/kg subq. subq.

For pts >=75, no IV bolus and reduce subq dose to 0.75 mg/kg For pts >=75, no IV bolus and reduce subq dose to 0.75 mg/kg

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Clopidogrel in STEMIClopidogrel in STEMI

Class I - Clopidogrel 75mg/ day should be Class I - Clopidogrel 75mg/ day should be added to ASA in pts with STEMI regardless of added to ASA in pts with STEMI regardless of fibrinolytic use LOE Afibrinolytic use LOE A

Class IIa - In patients < 75yo, it is reasonable Class IIa - In patients < 75yo, it is reasonable to consider a loading dose of 300mg LOE C to consider a loading dose of 300mg LOE C

- - recent studies suggest a loading dose of Plavix 600mgrecent studies suggest a loading dose of Plavix 600mg

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Questions?Questions?