Current Management of Current Management of Acute Coronary Syndrome in aAcute Coronary Syndrome in a

Non- Interventional Center Non- Interventional Center

DefinitionDefinition

• Acute Coronary Syndrome:

Any constellation of clinical symptoms that are compatible with acute myocardial ischemia.

It encompasses AMI (ST-segment elevation and depression, Q wave and non-Q wave) as well as Unstable angina.

Acute Coronary Syndromes

Unstable Angina

Ischemic Chest Discomfort

No ST Elevation ST Elevation

Non -ST Elevation MI

ST Elevation MI

ECG

Cardiac markers– +

Golden Hour

• Maximum damage to heart muscle

• Maximum efficacy of treatment seen

• Survival is best if clot buster drugs given within this

period

“Time is muscle and muscle is time”

Process of care in emergency Process of care in emergency department: 4 D’s department: 4 D’s

• Timed 0: onset of symptoms

• ED time 1: Door [arrival at ED]

• ED time 2: Data

[initial ECG]

• ED time 3: Decision

[to administer thrombolytics]

• ED time 4: Drug

[infusion of thrombolytic started

Time interval 1

Time interval 2

Time interval 3

Door

To

Drug

time

Door to Needle timeDoor to Needle time• < 30 min in 33% patients only• Adjusted odds ratio of death if Door to Needle time

was – 61 - 90 min = 11%

– > 90 min = 23 %

• 11-23 % increased odds of developing EF < 40% if Door to Needle time was > 30 min.

• Door to Ballon time > 2 hrs was ass. with 41-62 % increase in adjusted odds ratio of death.

Reducing treatment delaysReducing treatment delays

• EMS system• Ambulance transport• Pre-hospital ECGs• Pre-hospital thrombolysis : only when a

physician is present or if pre-hospital transport time is > 6o min

• Heart attack awareness campaign

Emergency Room Triage in Emergency Room Triage in ACSACS

• Initial presentation

• 12 Lead ECG

• Cardiac Enzymes

TRIAGE OF ACSIschemic Chest Discomfort

ST Elevation or New LBBB

ECG s/o IschemiaST dep, T inversion

Non-diagnostic or Normal ECG

Assess initial ECG

Aspirin Baseline CK, CK-MB

Assess C/I to thrombolysis Anti-ischemic therapyReperfusion therapy [ thrombolyse or Primary PTCA ]

AdmitAnti-ischemic therapy

Serial cardiac markers2D Echo

E/o ischemia / MI

No Yes

DischargeAdmit

Goal 10 minutes

Goal < 30 min for STK or < 60 min for arrival in Cath Lab for PTCA

Biomarkers + of the following

Pathological findings of AMI

Typical symptoms of AMI + one of

the followingProcedural

myocardial damage

Typical symptoms of myocardial ischemia

No other findings required

ST segment elevation in the ECG

cardiac biomarkers to prespecified levels; symptoms may be absent; ECG changes absent/nonspecific

Q waves in the ECG   Increased levels of cardiac biomarkers

 

ST segment elevation or depression in the ECG

     

Modified from Alpert J, Thygesen K, et al: Towards a new definition of myocardial infarction for the 21st century. J Am Coll Cardiol 2000, in press.

Criteria For The Diagnosis Of Acute Myocardial Infarction (AMI)

Initial PresentationInitial Presentation

Common Symptom History In Acute MICommon Symptom History In Acute MI

Chest PainLocation

Usually substernal

Quality Crushing or squeezing

Radiation Either Arm, Neck, Jaw,

Epigastrium,Or between Scapulae

Duration Generally 30 minutes to

several hours

Chest PainLocation

Usually substernal

Quality Crushing or squeezing

Radiation Either Arm, Neck, Jaw,

Epigastrium,Or between Scapulae

Duration Generally 30 minutes to

several hours

Anginal Pain Equivalents• Dyspnoea

• Marked weakness

• Syncope

• Accompanied diaphoresis, nausea, vomiting

No pain ; No gainNo pain ; No gain• In national registry of myocardial infarction [NRMI]

435,000 patients with proven acute MI, chest pain was absent at initial presentation [33%]

• These pts were at least 7 years older; higher proportion were women[49% vs 38%]; diabetics;

had h/o prior heart failure had longer delay before hospital admission; were less likely to receive thrombolysis or primary PTCA;

b-blockers, aspirin or heparin Had higher in-hospital mortality [23.3% vs 9.3%]

Recognition of High Risk CasesRecognition of High Risk Cases

• Demographic and historical factors associated with poor

prognosis

– Age > 70 years

– Female gender

– History of Diabetes mellitus

– Prior angina pectoris

– Previous MI

Peterson ED et al. Ann Intern Med 126:561-582,1997

ElectrocardiogramElectrocardiogram“standard of care”“standard of care”

ECG PatternsECG Patterns

Normal38%

ST Depression

18%

T Inversion

23%

ST Elevation

11%

LBBB

10%

Hamm et al. NEJM 1997;337

ST Depression

57%

Normal13%

T Inversion

13%

ST Elevation

17%

TIMI IIIb Investigators, Circulation 1994;89

In Acute Chest Pain In unstable angina

Prognostication through ECG Prognostication through ECG

• ST elevation • decisive role regarding thrombolytic therapy

• Worse prognosis / Increase mortality in• Anterior MI > Inferior MI

• RVMI complicating IWMI

• Multiple leads with ST elevation & high sum of ST elev.

• Persistent advanced heart block

• New IVCD (Bifascicular / trifascicular)

• Persistent ST depression / Q waves in many leads

• ST depression in anterior leads in IWMI

NEJM 330:1211-1217, 1994 , Ann Intern Med 126:556;1997

Risk of MI/Death during 1 yr Followup Risk of MI/Death during 1 yr Followup based on ECG on Admissionbased on ECG on Admission

0

5

10

15

20

25

30

60 120 180 240 300 360

Follow Up ( Days)

MI

or D

eath

(%

) ST Elev + Dep

ST Dep

ST Elev

T Inv

NO ST/T Changes

The RISC Study Group . J.Intern.Med.1993;234

Limitations of ECGLimitations of ECG

1. It provides a snapshot view of a highly dynamic process.

2. Lack of perfect detection in areas of myocardium it supplies.

3. Small areas of ischemia or infarction may not be detected.

4. Conventional leads do not directly examine right ventricle,

posterior basal or lateral walls very well.

5. Baseline changes like BBBs, early repolarization, LVH, &

arrhythmias make interpretation difficult.

6. AMI in LCx territory are likely to have non-diagnostic ECG.

7. ECG is not very sensitive test & should always be considered a

supplement to , rather than a substitute for, physician judgment.

Pseudo-infarction on ECGPseudo-infarction on ECG

• LVH

• Conduction disturbance

• Pre-excitation

• Primary myocardial disease

• Traumatic heart disease

• Pericarditis

• Early repolarization

• Pneumothorax

• Pulmonary embolism

• I/C hemorrhage

• Hyperkalemia

• Amyloidosis

• Sarcoid cardiac involvement

Cardiac MarkersCardiac Markers

MARKER MW (D)

TIMES TO INITIAL

ELEVATION (hr)

MEAN TIME TO PEAK

(NONTHROMBOLYSIS)

TIME TO RETURN TO

NORMAL RANGE

MOST COMMON SAMPLING SCHEDULE

hFABP 14,000-15,000 1.5 5-10 hr 24 hr On presentation, then 4 hr later

Myoglobin 17,800 1-4 6-7 hr 24 hr Frequent; 1-2 hr after CP

MLC 19,000-27,000 6-12 2-4 d 6-12 d Once at least 12 hr after CP

cTnI 23,500 3-12 24 hr 5-10 d Once at least 12 hr after CP

cTnT 33,000 3-12 12 hr-2 d 5-14 d Once at least 12 hr after CP

MB-CK 86,000 3-12 24 hr 48-72 hr Every 12 hr×3

MM-CK tissue isoform

86,000 1-6 12 hr 38 hr 60-90 min after CP

MB-CK tissue isoform

86,000 2-6 18 hr Unknown 60-90 min after CP

Enolase 90,000 6-10 24 hr 48 hr Every 12 hr×3

LD 135,000 10 24-48 hr 10-14 d Once at least 24 hr after CP

MHC 400,000 48 5-6 d 14 d Once at least >2 d after CP

hFABP=heart fatty acid binding proteins; MLC=myosin light chain; cTnI=cardiac troponin I; cTnT=cardiac troponin T; MB-CK=MB isoenzyme of creatinine kinase (CK); MM-CK=MM isoenzyme of CK; LD=lactate dehydrogenase; MHC=myosin heavy chain; CP=chest pain

Appearance of Cardiac Markers in Blood Versus

Time After Onset of Symptoms.

• Peak A: Myoglobin or CK-MB isoforms post AMI

• Peak B: cardiac troponin post AMI

• Peak C: CK-MB post

AMI

• Peak D: cardiac troponin after unstable angina.

Predictive Value of Troponin Rapid Testing

Predischarge TMT + Troponin

• If Both Normal--1 % risk of Death /MI at 5 Months

• If both Abnormal --50 % risk of death/MI at 5 Months

TroponinsTroponins

• 30% patients with rest pain without ST- elevation and were diagnosed as unstable angina based on CPK_MB results are found to have elevated troponins, converting these to NSTEMI.

Clinical StatusClinical Status

GISSI-1 (%)

Killip Definition Incidence ControlLyticClass MortalityMortality

I No CHF 71 7.3 5.9

II S3 gallop or 23 19.9 16.1basilar rales

III Pulmonary edema 4 39.0 33.0(rales >1/2 up)

IV Cardiogenic shock 2 70.1 69.9

Killip T et al. Am J Cardiol 20:457;1967GISSI. Lancet 1”397-401, 1986

Hospital PhaseHospital Phase

Hospital Phase : ToolsHospital Phase : Tools

Risk stratification in CCU is done by– Clinical findings

– ECG monitoring

– Invasive hemodynamic monitoring

– LV Function - most important determinant of hospital mortality

– Echocardiography – LVEF, diastolic function, hemodynamics, degree of MR, mechanical complications

Hemodynamic ClassificationHemodynamic Classification

Subset Definition PCWP CI Mortality

I Normal hemodynamics <18 >2.2 3%

II Pulmonary Congestion >18 >2.2 9%

III Peripheral hypoperfusion <18 <2.2 23%

IV Pulmonary congestion & Peripheral hypoperfusion

>18 <2.2 51%

Forrester J et al. NEJM 295:1356:1976

EchocardiographyEchocardiography

• Identification of location of infarction• Estimation of infarct size• Determination of LVEF• Assessment of diastolic function• Degree of MR• Recognition of mechanical complications

LVEF < 40% within 72 hrs of onset of AMI is associated with increase risk of death

Berning et al. Am J Cardiol 69:1538-44;1992

EchocardiographyEchocardiography• Greater number of WMA correlated with

• higher Killip class,

• lower pO2,

• higher CPK levels and

• larger number of Q waves on ECGRomano et al

• 30 day mortality – WMA < 3 segments 3.5%

– WMA 4-6 segments 12.9%

– WMA 7-9 segments 18.3%

– WMA > 9 segments 37.8%

Am J Cardiol 81(12A):13G-16G;1998

Normal

RelaxationDefect

Pseudo-Normalization

Restrictive pattern

Mitral inflow patternsMitral inflow patterns

A

E

•Worse is the flow pattern, worse is the prognosis

•A deceleration time < 130 msec indicates future development of CHF

Poulsen et al , Eur Heart J 1997;18:1882

ComplicationsComplications

• LV systolic dysfunction

• RuptureFree WallFree Wall

VSDVSD

Papillary muscle rupture

Papillary muscle rupture

Subepicardial

aneurysm

Subepicardial

aneurysm

LV LV ANEURYSMANEURYSM

MRMR

CARDIAC RUPTURECARDIAC RUPTURE VSD.VSD.

ComplicationsComplications• Mitral regurgitation LV dilatationLV dilatation

Papillary muscle dysfunction

Papillary muscle dysfunction

Papillary muscle rupture

Papillary muscle rupture

LV thrombus

LV thrombus

Pericardial effusion/tamponade

Pericardial effusion/tamponade

RVinfarctRVinfarct

LV outflow tract obstructionLV outflow tract obstruction

Echo: value in ACSEcho: value in ACS

• Echo provides new and useful information in 29% of the

patients admitted to CCU

• Decision about reperfusion strategy

• ACE-I therapy (SAVE trial)

• Unrecognized prior MI

• Titrating beta-blockers

• Need for invasive monitoring

• Standby IABP support

ManagementManagement

• Goals • Immediate relief of

ischemia • Prevention of serious

adverse outcomes

• Approach • Anti-ischemic therapy• Anti-platelet therapy• Anti-coagulant

therapy• Ongoing risk

stratification• Invasive procedures

Anti-Ischemic therapy for Anti-Ischemic therapy for Continuing IschemiaContinuing Ischemia

• Bed rest with ECG monitoring

• O2 to maintain SaO2 >90%

• NTG IV• Beta-blockers• Morphine

• IABP if ischemia or hemodynamic instability persists

• ACE I for control of hypertension or LV dysfunction, after MI

Class-I Recommendations, ACC/AHA practice guidelines

Anti Ischemic TherapyAnti Ischemic Therapy

• Nitrates

• Beta Blockers

• Calcium Channel Blockers

NITRATES IN ACSNITRATES IN ACS

No.Of Pts.

Mortality (%)Study Year

Tt Control

GISSI 3 94 18895 6.5 6.9

ISIS-4 95 58050 7.3 7.5

Beta Blockers in ACSBeta Blockers in ACS

MortalityStudy Year n

Tt C

MIAMI * 1985 5578 4.3 4.9

ISIS-1# 1986 16027 3.9 4.6

* Eur H Journal 1985;6# Lancet 1986;ii

Calcium Ch. Blockers in ACSCalcium Ch. Blockers in ACS

MortalityStudy Yr N

Tt C

Metaanalysis

1989 7351 5.9 5.2

Salim Yusuf, BMJ 1989; 299

Antiplatelet and Antiplatelet and Anticoagulation TherapyAnticoagulation Therapy

Oral Antiplatelet therapy• Aspirin

– Thienopyridines Ticlopidine Clopidogrel

• Heparins – UFH

– LMWH

IV Antiplatelet therapy • Abciximab• Eptifibatide• Tirofiban

Anticoagulants Anticoagulants Unfractionated Heparin (UFH)Unfractionated Heparin (UFH)

• Most widely used antithrombotic agent

• Recommendation is based on documented efficacy in many trials of moderate size

• Meta-analyses of six trials showed a 33% risk reduction in MI and death, but with a two fold increase in major bleeding

Unfractionated Heparin (UFH)Unfractionated Heparin (UFH)

• Disadvantages include: • Poor bioavailability • No inhibition of clot-bound thrombin • Dependent on antithrombin III (ATIII) cofactor• Frequent monitoring (aPTT) to ensure therapeutic

levels • Rebound ischemia after discontinuation • Risk of heparin-induced thrombocytopenia (HIT)

Low-Molecular-Weight Low-Molecular-Weight Heparin (LMWH)Heparin (LMWH)

• Fraction of standard (UFH) heparin• Advantages over UFH: • Greater bioavailability • No need to closely monitor• Resistant to inhibition by activated platelets • Lower incidence of HIT Enhanced anti-factor Xa

activity• Effective subcutaneous administration • Enoxaparin, dalteparin, reviparin, nadroparin, fraxiparin

Role of Anticoagulants in ACSRole of Anticoagulants in ACS

Mortality %Study Yr N

Tt c

UFH[Meta-analysis]

1994 1353 6.5 6.9

LMWH[FRISC 1]

1996 1506 1.8 3.8

New Anti coagulants in ACSNew Anti coagulants in ACSMortality%

Study Yr N

Tt c

LMWS

FRISC 1997 1482 3.9 3.6

ESSENCE 1997 3171 6.2 7.7

TIMI 11B 1998 3940 5.7 6.8

HIRUDINGUSTO IIb 1996 8011 8.3 9.1

OASIS 2 1998 10141 3.5 4.2

ESSENCE Trial ESSENCE Trial (Efficacy and Safety of Subcutaneous Enoxaparin (Efficacy and Safety of Subcutaneous Enoxaparin

in non-Q-Wave Coronary Events Study)in non-Q-Wave Coronary Events Study)

• LMWH (enoxaparin)+ASA vs UFH+ASA

• Patients:  angina at rest or non-Q-wave MI;

• n = 3,171

• Composite triple endpoint:  death/nonfatal MI/RA

ESSENCE Trialincidence of death, MI, or recurrent angina

N Eng J Med 1997;337:447-452

0

5

10

15

20

25

0

5

10

15

20

25

heparin enoxaparin Heparin enoxaparin

n=1564 n=1607 n=1564 n=1607

19.8%

16.6% P=0.019

23.3%

19.8% P=0.016

Day 14 Day 30

AntiThrombotic Tt for ACSAntiThrombotic Tt for ACS

• Anticoagulants– Heparin

• UFH

• LMW

– Hirudin

– Coumarins

• Antiplatelets– Aspirin

– Ticlopidine

– Gp IIb/IIIA Inhibitors

• Thrombolytics

Anti Platelet Tt in ACSAnti Platelet Tt in ACS

• Aspirin - - Inhibits cyclo-oxygenase in platelets

• Ticlopidine --- Inhibits the ADP receptor on the platelet surface

• Gp iib/iiia receptor antagonist

AspirinAspirin

• In AMI, ASA reduced the risk of death by 20-25% In UA, ASA reduced the risk of fatal or nonfatal MI by 71% during the acute phase, 60% at 3 months, and 52% at 2 years

Incidence of Ischemic Events

0

2

4

6

8

10

12

14

16

No aspirin(early 1980s)

Aspirin Aspirin + Heparin

16%

12%

9%

Incidence of death and MI

• Not Perfect

• Patients on ASA may present with ACS

• ASA non-responders 20-30%

• Not adequate alone for stent implantation

• Side effects

ThienopyridinesThienopyridines

• Ticlopidine

• Clopidogrel – Block ADP receptor resulting in inhibition of

transformation of GP IIb/IIIa into its high affinity state

Aspirin & Ticlopidine in ACSAspirin & Ticlopidine in ACS

MortalityStudy Yr NTt C

ASPIRINVA 1983 1342 6.4 10.8

ISIS 2 1988 5409 7.3 8.2

RISC 1990 796 6.5 17.1

TICLOPIDINEBalsano 1990 652 4.5 6.2

CAPRIE CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events)(Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events)

• 19,185 patients randomly assigned to clopidogrel (75 mg/d) or to aspirin (325 mg/d)

• Entry criteria: recent MI, recent ischemic stroke and symptomatic PAD

• Follow up for 1-3 years• 8.7% RR in the combined incidence of stroke, MI, or death

(P=.043) with clopidogrel • Patients with MI did better with aspirin • Patients with PVD or stroke did better with clopidogrel

Lancet 1996;348:1329-1339

CURECURE• Randomized, double-blind, parallel group,

clinical trial of clopidogrel vs placebo in patients with ACS

• All patients receive ASA (75-325 mg) • International trial (28 countries)• 12,562 patients (482 Hospitals) Central

randomization• 3-12 month Rx and follow-up • Main outcomes: CV death/MI, stroke + refractory

ischemia

Clopidogrel in Unstable Angina to Prevent Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE)Recurrent Ischemic Events (CURE)

• Clopidogrel is a class I indication for treatment unstable angina, even when early coronary intervention is not being considered.

• The treatment might be continued for at least 9 months.

• • If a coronary intervention is performed, clopidogrel should be started at

300 mg and continued for at least 1 month at 75 mg/d. In patients not at high risk for bleeding, clopidogrel should probably be continued for 9 months.

• Clopidogrel has been associated with rare cases of thrombotic thrombocytopenic purpura.

• If patients cannot tolerate aspirin or clopidogrel, warfarin (Coumadin) can be used and titrated to an international normalized ratio of 2.0 to 3.0 in post–myocardial infarction patients.

New AgentsNew Agents• Other antithrombin agents such as lepirudin (Refludan),

argatroban (Novastan), and the low-molecular-weight heparin

dalteparin (Fragmin) need further study before they can be

recommended in this setting.

• Newer drugs are currently under investigation, including

nicorandil, * trimetozine † , and fasudil † .

• Newer markers for prognosis and stratification of patients

with angina pectoris include• Brain natriuretic peptide (TIMI-16)

• Annexin B.

Thrombotic Process – PathophysiologyPlatelet Aggregation

Thrombotic Process – PathophysiologyPlatelet Aggregation

Ruptured PlaqueRuptured Plaque

FibrinogenFibrinogen

VWF

VWF VW

FVW

FGP GP IIIIb/b/IIIIIIa a ReceptorReceptor

GP GP IIb b ReceptorReceptor

IV Anti-platelet TherapyIV Anti-platelet Therapy

• GP IIb/IIIa inhibitors

• abciximab (monoclonal antibody)

• eptifibatide (peptide inhibitor)

• lamifiban and tirofiban (non-peptides)

•Conclusive evidence of early benefit of GP IIb/IIIa inhibitors during medical treatment in acute coronary syndromes without persistent ST-segment elevation.

•In addition, in patients subsequently undergoing PCI, GP IIb/IIIa inhibition protects against myocardial damage associated with the intervention.

Abciximab in ACSAbciximab in ACS

Death %Study YR N

Tt C

PARAGON 1998 2282 11.3 11.7

PRISM 1998 3232 5.8 7.1

PRISMPLUS

1998 1915 8.7 11.9

PURSUIT 1994 10948 14 15.7

IV GP IIb/IIIa ACS Trials IV GP IIb/IIIa ACS Trials (1998-2000)(1998-2000)

• Patients undergoing PCI have the greatest reduction in events

• Little data to support use to reduce complications in the absence of PCI

• Should be used in high risk patients (ST changes, elevated troponin, refractory symptoms) as a bridge to catheterization

Recommendations for Antiplatelet & Anticoagulation Recommendations for Antiplatelet & Anticoagulation TherapyTherapy

• Class I 1. Antiplatelet therapy should be initiated promptly.

Aspirin is the first choice and is administered as soon as possible after presentation and is continued indefinitely. (Level of Evidence: A)

2. Clopidogrel should be administered to patients who are unable to take ASA because of hypersensitivity or major gastrointestinal intolerance. (Level of Evidence: A)

3. In hospitalized patients in whom an early noninterventional approach is planned, clopidogrel should be added to ASA as soon as possible on admission and administered for at least 1 month (Level of Evidence : A) and for upto 9 months (Level of Evidence : B)

4. In hospitalized patients for whom a PCI is planned, clopidogrel should be started and continued for at least 1 month (Level of Evidence : A) and for up to 9 months in patients who are not at high risk for bleeding (Level of Evidence : B)

5. In patients taking clopidogrel in whom CABG is planned, if possible the drug should be withheld for at least 5 days, and preferably for 7 days. (Level of Evidence :B)

6. Anticoagulation with subcutaneous LMWH or intravenous UFH should be added to antiplatelet therapy with ASA and/or clopidogrel. (Level of Evidence : A)

7. A platelet GP IIb/IIIa receptor antagonist should be administered, in addition to ASA and heparin, to patients in whom catheterization and PCI are planned. The GP IIb/IIIa antagonist may also be administered just prior to PCI (Level of Evidence: A)

Early Conservative vs Invasive StrategiesEarly Conservative vs Invasive Strategies

Recommendations Class IRecommendations Class I 1. An early invasive strategy in patients with UA/NSTE-MI

and any of the following high risk indicators. (Level A) • Recurrent angina/ischemia at rest or with low-level activities despite

intensive anti-ischemic therapy

• Elevated TnT or TnI

• New or presumably new ST-segment depression

• Recurrent angina/ischemia with CHF symptoms, an S3 gallop, pulmonary edema, worsening rales, or new or worsening MR

• High-risk findings on noninvasive stress testing

• Depressed LV systolic function (EF < 0.40)

• Hemodynamic instability

• PCI within 6 months

• Prior CABG

2. In the absence of these findings, either an early conservative or an early invasive strategy in hospitalized patients without contraindications for revascularization (Level of Evidence: B)

CASE 1• 64 years, male presented with

worsening angina for 2 weeks

• ST depression inferiorly

• Cardiac enzymes negative

• Pre-treated with clopidogrel, in addition to ASA, UFH, metoprolol, ISDN and atorvastatin

CASE 2• 62 years old female with

HTN, DM, CABG

• NSTEMI 10 days earlier

• Initially treated with early conservative approach

• Transferred due to recurrent angina (PIA)

Post discharge Care

“ABCDE”

• A – Antiplatelets & Antianginals

• B – Beta blocker, Blood pressure control

• C – Cholesterol lowering, Cigarettes cessation

• D – Diabetes control, Diet

• E – Education & Exercise

Future DirectionsFuture Directions

• CURE Study --- Role of Clopidogrel + Aspirin vs Aspirin alone

• GUSTO 4 -- Abciximab

• SYMPHONY --- Sidrafiban in ACS

• OASIS-2 --- Warfarin

INDICATIONS OF PRIMARY PTCAINDICATIONS OF PRIMARY PTCA

• Cardiogenic Shock

• Large area of myocardium at risk

• Thrombolysis contraindicated

• Alternative to thrombolysis

Interventions in ACSInterventions in ACS

Rationale

• Prognosis of ACS is worse than Stable angina

• Inhospital death / Reinf. = 5 - 10 %

• Ist Mo Death / Reinf. = 5 - 10 %

PTCA in ACSPTCA in ACS

TIMI III B

1473 pts randomised

Early Invasive Conservative

Mortality/Reinf 6 wks 7.2 % 7.8 %

1 Yr 10.8% 12.2%

PTCA in ACSPTCA in ACS

VANQWISH TRIAL

916 Pts. Of UA

Early Invasive Conservative

24 % 19% 1 yr Mortality or Reinf

PTCA in ACSPTCA in ACS

FRISC 2

2457 Pts of ACS

Early Invasive Tt Selective Invasive Tt

9.5 % 12 %6 Mo Deathor Reinf.

Procedural 1.2 % 0.4 % Mortality

CABG in ACSCABG in ACS

Study Yr N Periop.Mortality

LongTermMort.

FollowUp(mo)

Rahimtoola 1983 1282 1.8% 17% 120

CASS 1985 3311 3.9 21 84

Parisi 1989 231 4.1 16 60

Future DirectionsFuture Directions

• RITA 3 - is comparing early invasive Tt with conservative tt. In ACS, in pts ttd. With LMWs

• TACTICS- Early invasive vs conservative tt

TIMI 18 with IV UFH Heparin + IV ReoPro

EMERGENCYEMERGENCYROOMROOMPROTOCOLPROTOCOLFORFORACUTEACUTECHEST CHEST PAINPAIN

Phases & Lesion Morphology Phases & Lesion Morphology of Atherosclerosisof Atherosclerosis

American Heart Assn. Committee on Vascular Lesions

AMI: Parameters influencing prognosisAMI: Parameters influencing prognosis

AcuteMI

AtPresentation

InHospital

AtDischarge

Size of infarct

Recurrentischemia

LV systolic dysfunction

Diastolicdysfunction

Mechanicalcomplications

Residualischemia

LV dysfunction

Risk of arrhythmia

AgeGender

ECGfeatures

ConcomitantRisk factors

Clinicalstatus

TIMI myocardial perfusion TIMI myocardial perfusion grade and mortalitygrade and mortality

Second International Study of Infarct Second International Study of Infarct Survival (ISIS-2).Survival (ISIS-2).

Mortality differences during days 0 to 35 subdivided by Mortality differences during days 0 to 35 subdivided by presentation features in nine trials of thrombolytic therapypresentation features in nine trials of thrombolytic therapy

TIMI Risk Score for STEMI for predicting TIMI Risk Score for STEMI for predicting 30-day mortality30-day mortality

Acute Coronary SyndromesAcute Coronary SyndromesSpectrumSpectrum

Acute Coronary Syndromes

No ST elevation ST elevation

Enzymes not Enzymes

USA NSTEMI

STEMI

Treatment of ACSTreatment of ACS• All patients receive aspirin • Clopidogrel is also favored as an adenosine-mediated platelet blocker,

particularly in patients with aspirin allergy.• ESSENCE trial (Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q

Wave Coronary Events) has suggested a preference for LMWH specifically, enoxaparin (Lovenox) over unfractionated heparin in ACS

• Finally, a platelet glycoprotein IIb/IIIa inhibitor is needed. • Glycoprotein IIb/IIIa receptor blockers have been studied with simultaneous use

of unfractionated heparin and aspirin. Most of the trials with these agents have involved coronary interventions and have shown significant benefit.

• If no intervention is planned, abciximab is not indicated. • Currently, tirofiban and eptifibatide are useful in patients with continuing

ischemia when no percutaneous intervention is planned. These latter two medications are also indicated in patients with continuing ischemia or other high-risk features in whom a percutaneous intervention is planned.

Rx of ACSRx of ACS

• TACTICS trial and TIMI-18 compared an early invasive and a conservative strategy in patients treated with the tirofiban & showed that an early invasive strategy reduces the incidence of major cardiac events.

• The data for high-risk AMI and non–Q wave MI suggest that angiography should be part of the early plan.

• The data for unstable angina with no elevation in biochemical markers are less clear.

• Because of cost considerations, abciximab with coronary intervention is recommended in high-risk patients.

• In intermediate-risk patients, regardless of whether they are candidates for coronary intervention, tirofiban or eptifibatide is recommended.

• Low-risk patients may not require either of these agents, but they should receive heparin, probably low molecular-weight heparin, aspirin, and clopidogrel at a dose of 300 mg to start and then 75 mg/d for at least 30 days.

• In addition, a “statin” should be started in that hospitalization (MIRACL) if LDL cholesterol is greater than 130 mg/dL.

Antithrombotic Drug Therapy

Abciximab (ReoPro) with unfractionated heparin and aspirin

0.25-mg/kg intravenous bolus followed by an infusion of 0.125 μg/kg/min for 12–24 h up to 10 mg/min

Eptifibatide (Integrilin) with unfractionated heparin and aspirin

180-μg/kg bolus followed by an infusion of 2 μg/kg/min up to 72 h for intervention. Max 15 mg/h

Tirofiban (Aggrastat) with unfractionated heparin and aspirin

0.4 μg/kg/min × 30 min 0.1-μg/kg/min infusion × 48 h up to 108 h (PRISM-Plus)

Enoxparin (clexane) 1 mg/kg q12 h

Clopidogrel (Plavix) 300 mg initially, followed by 75 mg/d

Findings in High-Risk Patients

• Recurrent ischemia at rest or low levels of activity with

medical management

• High-risk noninvasive stress testing with depressed

ejection fractions,

• Extensive wall motion abnormalities

• Hemodynamic instability

• Sustained ventricular tachycardia

• Recent revascularization with coronary intervention or

coronary bypass graft surgery

The GUSTO Pyramid: 30 Day Mortality Model

Age (31%)Age (31%)Age (31%)Age (31%)

Systolic Blood Pressure (24%)Systolic Blood Pressure (24%)Systolic Blood Pressure (24%)Systolic Blood Pressure (24%)

Killip Class (15%)Killip Class (15%)Killip Class (15%)Killip Class (15%)

Heart Rate (12%)Heart Rate (12%)Heart Rate (12%)Heart Rate (12%)

MI Location (6%)MI Location (6%)MI Location (6%)MI Location (6%) Prior MI (3%)Prior MI (3%)Prior MI (3%)Prior MI (3%)

Age x Killip (1.3%)Age x Killip (1.3%)Age x Killip (1.3%)Age x Killip (1.3%) Height (1.1%)Height (1.1%)Height (1.1%)Height (1.1%)

Diabetes (1%)Diabetes (1%)Diabetes (1%)Diabetes (1%) Time-to-Rx (1%)Time-to-Rx (1%)Time-to-Rx (1%)Time-to-Rx (1%)

Smoker (0.8%)Smoker (0.8%)Smoker (0.8%)Smoker (0.8%) Weight (0.8%)Weight (0.8%)Weight (0.8%)Weight (0.8%)

Accel t-PA (0.8%)Accel t-PA (0.8%)Accel t-PA (0.8%)Accel t-PA (0.8%)

Prior CABG (0.8%)Prior CABG (0.8%)Prior CABG (0.8%)Prior CABG (0.8%)

HTN (0.6%)HTN (0.6%)HTN (0.6%)HTN (0.6%)

H/oH/oCV DCV D

(0.4%)(0.4%)

H/oH/oCV DCV D

(0.4%)(0.4%)

Lee et al. Circulation

1995;91:1659-1668

Influence of Clinical characteristics on 30 day mortality in thrombolyzed

patients with STEMI

Initial Presentation : ClinicalInitial Presentation : Clinical

Initial PresentationInitial PresentationTIMI Risk Score for STEMI

Morrow et al. In TIME II substudy. Circulation 2000; 102:2031-2037

1 Yr MortalityScore 0 - 1%; Score >8 - 17%

Painful factsPainful facts

• 40-60% patients presenting to ER with chest pain and later having confirmed MI have non-diagnostic ECGs.

Roberts & Kleiman , Circ 1994;89:872-881

• 70-80% patients with non-Q MI present with ST depression only and 80% of these have subtotal coronary occlusion.

Boden et al, JACC 1987;9:61A