Acute Coronary Acute Coronary SyndromeSyndrome

Steven R. Bruhl MD, MSSteven R. Bruhl MD, MS33rdrd Year Cardiology Fellow Year Cardiology FellowInternal Medicine DidacticsInternal Medicine Didactics

July 14, 2010July 14, 2010

Goals and ObjectivesGoals and Objectives

Discuss the definition & pathophysiology of Discuss the definition & pathophysiology of ACSACS

Recognize the clinical features of low, Recognize the clinical features of low, intermediate and high risk ACSintermediate and high risk ACS

Be able to identify and treat patients Be able to identify and treat patients appropriate for a conservative or invasive appropriate for a conservative or invasive strategystrategy

Discuss new and controversial Discuss new and controversial pharmacological treatmentspharmacological treatments

Gold Standard for Treatment of ACS

ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation

Myocardial Infarction

http://circ.ahajournals.org/cgi/content/full/102/10/1193

Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2.

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

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%

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.

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----]----]

Decreased O2 Supply

•Flow- limiting stenosis

•Anemia

•Plaque rupture/clot

Increased O2 Demand

O2 supply/demand mismatch→Ischemia

Myocardial ischemia→necrosis

Pathophysiology ACS

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Pathophysiology of Stable Angina and ACSPathophysiology of Stable Angina and ACS

Pathophysiology of ACSPathophysiology of ACSEvolution of Coronary ThrombosisEvolution of Coronary Thrombosis

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

STEMISTEMI

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

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

Cardiac CatheterizationCardiac Catheterization

Name the only 3 situations that demand Name the only 3 situations that demand emergent cardiac catheterization.emergent cardiac catheterization.

Cardiac CatheterizationCardiac Catheterization

Name the only 3 situations that demand Name the only 3 situations that demand emergent cardiac catheterization.emergent cardiac catheterization.

STEMI or new LBBBSTEMI or new LBBB ACS with hemodynamic or electrical instability ACS with hemodynamic or electrical instability

despite despite optimaloptimal medical management medical management Uncontrolled CP despite Uncontrolled CP despite optimaloptimal medical medical

managementmanagement

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

Initial Evaluation and management Initial Evaluation and management of Non ST-elevation ACSof Non ST-elevation ACS

Initial Evaluation and Management

•History and Physical•ECG•Cardiac Biomarkers

Establish the Likelihood thatClinical PresentationRepresents an ACSSecondary to CAD

Risk Stratify for Short-termAdverse Outcomes

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)

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

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

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.

Risk Stratification by ECGRisk Stratification by ECG

CAVEATSCAVEATS

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.

Risk Stratification by ECGRisk Stratification by ECG

CAVEATS cont.CAVEATS cont. 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.

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

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

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.

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

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 cclosure of ASDs)losure of ASDs)2.2. CCongestive heart failure (ongestive heart failure (aacute and chronic)cute and chronic)3.3. AAortic valve disease and HOCM with significant LVHortic valve disease and HOCM with significant LVH4.4. HHypertensionypertension5.5. HHypotension, often with arrhythmiasypotension, often with arrhythmias6.6. Noncardiac surgery Noncardiac surgery 7.7. RRenal failureenal failure8.8. CCritically ill patients, especially with diabetes, respiratory failureritically ill patients, especially with diabetes, respiratory failure9.9. DDrug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms)rug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms)10.10. HHypothyroidismypothyroidism11.11. CCoronary vasospasm, including apical ballooning syndromeoronary vasospasm, including apical ballooning syndrome12.12. IInflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, nflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, 13.13. PPost-PCI ost-PCI 14.14. PPulmonary embolism, severe pulmonary hypertensionulmonary embolism, severe pulmonary hypertension15.15. SSepsisepsis16.16. BBurns, especially if TBSA greater than 30%urns, especially if TBSA greater than 30%17.17. IInfiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and sclerodermanfiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma18.18. AAcute neurologic disease, including CVA, subarchnoid bleedscute neurologic disease, including CVA, subarchnoid bleeds19.19. RRhabdomyolysis with cardiac injuryhabdomyolysis with cardiac injury20.20. TTransplant vasculopathyransplant vasculopathy21.21. VVital exhaustionital exhaustion

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

Combined Sensitivities for ACSCombined Sensitivities for ACS

Early InvasiveEarly Invasive

ConservativeConservative

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

TIMI Risk Score

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

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 leads

A2:Aspirin use within the past 7 days; Age over 65

T: Two or more episodes of CP within 2 hours

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%

Specifics of Early Hospital CareSpecifics of Early Hospital Care

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

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

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

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

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

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

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.

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

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

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

Invasive vs Conservative Invasive vs Conservative StrategiesStrategies

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

How Early is Early?How Early is Early?

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

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

Secondary PreventionSecondary PreventionClass IIIClass III

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

New and ControversialNew and ControversialDrug TherapiesDrug Therapies

Early Treatment with ClopidogrelEarly Treatment with Clopidogrel

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

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.”

Clopidogrel vs. PrasugrelClopidogrel vs. Prasugrel

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

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

Questions?Questions?