Final Copy NSTE-ACS for Presentation

7/30/2019 Final Copy NSTE-ACS for Presentation

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Risk stratification and medical

management of NSTE-ACS

(UA/NSTEMI )

Dr Sajeer K T


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- Plaque rupture or erosion with super imposed non-occlusive thrombus

-most common cause of UA/NSTEMI

Other mechanism:

- dynamic obstruction

: spasm of epicardial coronary artery

: dysfunction of coronaryendothelium

- Restenosis : post PCI interventions

- Inflammation

- Secondary UA:ed O2 demand or ed O2 supply

(tachycardia, fever, hypotension, or

anemia)

Pathophysiology


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Nonocclusive thrombus

UA/NSTEMI

occlusive thrombus

STEMI

Stable

plaque

v/sunstable

plaque


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UA/NSTEMI definition

Electrocardiographic ST-segment depression or prominent T-wave inversion

and/or positive biomarkers of necrosis (e.g., Troponins)

in the absence of ST-segment elevation

and in an appropriate clinical setting (chest discomfort or

anginal equivalent)

-Anderson et al. JACC Vol. 50, No. 7, 2007 ACC/AHA UA/NSTEMI Guideline RevisionAugust 14, 2007:e1157


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3 principal presentations of UA

NonST-elevation MI

- presents as prolonged, more intense

rest angina or angina equivalent


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Braunwald Clinical Classification of UA/NSTEMI

- Braunwald E: Unstable angina: A classification. Circulation 80:410, 1989.


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Rationale for Risk Stratification

1) selection of the site of care:- coronary care unit

- monitored step-down unit- outpatient setting

2) selection of therapy:- GP IIb/IIIa inhibitors

- invasive management strategy

Estimation of the Level of Risk- Focuses on history

- Physical findings

- ECG findings- Biomarkers of cardiac injury

(Cardiac specific Troponin)

- TIMI score


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Clinical Indicators of Increased Risk in

UA/NSTEMI


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Braunwald Clinical Classification of UA/NSTEMI

Data from TIMI III Registry: Scirica BM et al: Prognosis in the TIMI III Registry

according to the Braunwald unstable angina pectoris classification. Am J Cardiol

90:821, 2002

P= 0.057

P= 0.001


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ECG Indicators of Increased Risk

Transient (i.e.,


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Echocardiography

RWMA coupled with ECG changes - high risk indicator.

Echo identifies other parameters associated with adverse

prognosis- LA dilatation

- mitral regurgitation

- diastolic dysfunction

Assessment of LV systolic function, even with Troponin negative

status is an important predictor of long term risk.

( class 1 recommendation)


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Nuclear Cardiac Imaging

An abnormal rest myocardial imaging

indicates:

- high risk of MI

- cardiac death

- need for revascularization over next 12 months

Normal rest myocardial scan:

- low risk patients


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Risk assessment by cardiac

Biomarkers

Troponins - preferred marker


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Troponin I Levels to Predict the Riskof Mortality in Acute Coronary Syndromes


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Biomarkers contd

Markers of hemodynamicstress:

- BNP& NT- proBNP

Inflammation:

- CRP

- Myeloperoxidase

- PAPP-A

- Soluble CD-40 ligand

- IL-6


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Association between levels of BNP and mortality across the

spectrum of acute coronary syndrome in the OPUS-TIMI 16 study.


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C-Reactive protein (CRP)

TIMI 11 A trial :CRP level 1.55 mg/dL had higher mortality rate,

even those patients with negative troponin level

(5.8% v/s 0.36% , p= 0.006)

Patients with both elevated CRP and Troponin level

had highest mortality rates ( 9.1%)

FRISC II sub study

CRP >10 mg/L : increased risk of cardiac vascular

death at all troponin levels.


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Cardiac markersClinical Indicators of Increased Risk in UA/NSTEMI


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Combined risk assessment scores

TIMI

PURSUIT

GRACE


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Age 65 years

At least 3 risk factors for CAD

Prior coronary stenosis of 50%

ST-segment deviation on ECG presentation( ST deviation >0.5 mm)At least 2 anginal events in prior 24 hours

Use of aspirin in prior 7 days

Elevated serum cardiac biomarkers

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Variables Used in the TIMI Risk Score

The TIMI risk score is determined by the sum of the presence of the above 7

variables at admission.

1 point is given for each variable.

Primary coronary stenosis of 50% or more remained relatively insensitive to

missing information and remained a significant predictor of events.

- Antman EM, et al. JAMA 2000;284:83542


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The TIMI risk score for unstable angina/nonST elevation

MI: A method for prognostication and therapeutic decision-

making. JAMA 284:835, 2000.


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GRACE registry & GRACE score

A global registry of ACS patients from 94 hospitals in 14countries.

GRACE score:Can be used to predict the cumulative risk of death or

myocardial infarction in the period from admission to

hospital to six months after discharge

The tool is simple and applicable to patients across thecomplete spectrum of acute coronary syndrome


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Later Risk Stratification and Management

Low-risk patients:- early stress testing is performed

( Exercise ECG -1st choice non-invasive test)

Intermediate risk patients:managed with an early conservative strategy

(free of ischemia and heart failure for a minimum of 2 to 3 days )

stress testing

Sub maximal protocol

Target workload =5 METS, 70 % MPHR or symptom limited


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Stress echo

- in patients with resting STD (0.1 mV)

- LV hypertrophy

- Bundle branch block

- Intraventricular conduction defect

- Preexcitation, or digoxin.

Pharmacologic stress testing with imaging:

( when physical limitations preclude adequate exercisestress )(e.g., arthritis, amputation, severe peripheral vascular disease, severe

chronic obstructive pulmonary disease, or general debility).


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ACC/AHAA Recommendations for Non-invasive Risk Stratification


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Medical Management of

NSTE-ACS (UA/NSTEMI )


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Algorithm for management of NSTEACS


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Anti ischemic therapy and analgesic therapy

Bed rest with continuous ECG monitoring

Supplemental oxygen ( if spo2


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Nitrates should not be administered to

patients with:

Systolic pressure < 90 mm Hg or to 30 mm Hg

below baseline

Severe bradycardia(< 50 bpm)

Tachycardia (> 100 bpm) in the absence of

symptomatic heart failure

Suspected RV infarction.

Who have received a phosphodiesterase


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Anti ischemic therapy contd..

Oral beta-blocker therapy when hemodynamically

stable ( within the 1st 24 h)

Contraindications:

1) signs of HF

2) low out put state( SBP


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COMMIT Trial

(Lancet 2005;366:162232.)

- 45,852 patients within 24 h acute MI

93% STEMI or LBBB, 7% had NSTEMI

- Utility of IV beta blockade followed by oral was tested

(Up to 15 mg IV 50 mg po metoprolol daily v/splacebo)

- No decrease of composite primary outcomes

death, reinfarction, or cardiac arrest

- Modest reduction in re- infarctions and VF

Risk of cardiogenic shock especially with initial hemodynamicinstability


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Nondihdropyridine calcium channel blockers

- Verapamil

- Diltiazem

Contraindications for CCBs:

Severe LV dysfunction

Summary :

definitive evidence for a benefit of CCBs in UA/NSTEMI is

predominantly limited to symptom control.

DAVIT STUDY - ( Eur Heart J 1984; 5: 516-28)

Diltiazem Reinfarction Study - (N Engl J Med 1986; 315: 423-9)


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ACEI & ARBs

ACE inhibitor (orally within 1st 24 h) in patients with

- pulmonary congestion

- LVEF 40%

contraindications:

- hypotension

(SBP < 100 mm Hg or < 30mm Hg below baseline)

- known contraindications to ACEIs

ARBs: if intolerance to ACEI


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Antiplatelet therapy


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Antiplatelet therapy

Aspirin : as soon as possible (165-325 mg)

- (non enteric formulation orally or chewed).

-Continued indefinitely(75-162mg/d ) in pts whotolerate it.

Clopidogrel :

- loading dose -300mg

- daily maintenance dose 75mg

- Continued for at least 1 month and ideally up to 1 year.

class 1


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Four randomized trials showing the benefit of aspirin in UA/NSTEMI, in which the

incidence of death or MI was reduced by more than 50% in each of the four trials.The doses of aspirin in the four trials were 325 mg, 1300 mg, 650 mg, and75 mg

daily, indicating no difference in efficacy for aspirin across these doses

(Data from Lewis HD, et al: N Engl J Med 309:396, 1983; Cairns JA, et al: N Engl J Med

313:1369, 1985; Theroux P, et al: N Engl J Med 319:1105, 1988; RISC Group: Lancet

349:827, 1990.)


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Clopidogrel dosage:

initial loading dose of 300 to 600 mg clopidogrel is followedby a maintenance dose of 75 mg/day.

Initiation with only 75 mg daily will achieve the target levelof platelet inhibition after 3 to 5 days.

Loading dose of 300 mg will achieve effective platelet

inhibition within 4 to 6 hours.

Use of a 600-mg loading dose achieves a steady-state level

of platelet inhibition after just 2 hours.


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Benefit of clopidogrel in reducing cardiovascular death, MI, or stroke to 1year in the CURE trial conducted in patients with UA/NSTEMI and in

patients managed medically, with PCI or CABG.

The Clopidogrel in Unstable angina to prevent Recurrent ischemic Events [CURE]

Trial. Circulation 110:1202, 2004


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-rapidly acting , more potent thienopyridine.

-associated with less respose variability than clopidogrel

Dosage :

Prasugrel 60 mg should be given promptly and not

later than 1 hour after PCI once coronary artery

anatomy is defined.

Duration and maintenance dose :

Prasugrel 10 mg daily

Duration : Up to 12 months

Contraindications :

Elderly 75 years,

Body weight


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Prasugrel

Comparison of efficacy (top) and safety

(bottom) in the TRITONTIMI 38 trial,

which compared Prasugrel with clopidogrel

in patients with ACS undergoing PCI.

Comparison of prasugrel and clopidogrel

on the development of stent thrombosis.

ARC = Academic Research Consortium.

TRITON TIMII 38 Trial


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GPIIb/IIIa Inhibitor

Upstream strategy:

Eptifibatide or tirofiban is administered in the ED or

hospital for medical stabilization usually in an

anticipation for an early invasive approach.

Adjunctive strategy:

Use either Eptifibatide or Abciximab as adjunctivetherapy immediately before PCI


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The routine upstream administration of GP IIb/IIIa inhibitors

did not improve the primary outcome of death or myocardial

infarction (MI) at 30 days and significantly increased

bleeding.

EARLY ACS trial

( in 9492 pts with UA/NATEMI)

Upstream glycoprotein (GP) IIb/IIIa inhibitor

V/S

Adjunctive strategy GP IIb/IIIa inhibitor


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Anti coagulant therapy recommendationsClass I

Conservative strategy:

- UFH or Enoxaparin

- Fondaparinux

( preferable in pts with increased risk of bleeding)

Enoxaparin or fondaparinux preferable to UFH unless CABG

is planned with in 24 hrs Class IIa

Invasive strategy:- UFH

- Enoxaparin

- Bivalirudin


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Unfractionated heparin (UFH)

- ACC/AHA Guidelinesrecommend weight adjusted dose

: 60 units/kg bolus (maximum 4000 u)

: 12 units/kg/hr infusion (1000 units/hour).

- Most of trials continued therapy for 2 to 5 days.

- (Optimal duration of anticoagulation remainundefined.)

UFH / E i


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Systematic overview of death/MI at 30 days including 21946 patients enrolled insix trials comparing enoxaparin with UFH .

Overall, a significant reduction in death or MI was observed (10.1% vs 11.0%)

(Petersen JL, et al. Efficacy and bleeding complications among patients randomized to enoxaparin orunfractionated heparin for antithrombin therapy Non STE ACS: a systematic overview. JAMA

2004;292:89, 96)

UFH v/s Enoxaparin

F d i


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Fondaparinux

OASIS- 5 trial:

The rate of major bleeding was reduced significantly

almost by halfin the fondaparinux arm

(Fondaparinux arm 2.2%) versus (4.1% enoxaparin arm).

In patients undergoing PCI, fondaparinux has associated

with more than a 3 fold increased risk of catheter-related

thrombi.

It is recommended only in patients at a higher risk

of bleeding who are managed conservatively

ACUITY TRIAL


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Bivalirudin.

Composite

ischemia

end point at30d

Ischemia

end point by

clopidogrelloading

before PCI at

30d

Ischemia

end point by

No clopidogrel

loading before

PCI at 30d

Major

bleeding at

30 days

ACUITY TRIAL

Bivalirudin

alone

UFH+

GPIIb/IIa

Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY)

trial was a complex trial performed in 13,819 patients with UA/NSTEMI, all

of whom underwent cardiac catheterization within 72 hours


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Treatment strategies and interventions

1. Early invasive strategy:Routine CAG

PCI, CABG, Medical Mx

2. Conservative approach:

Medical Mx

Recurrent Ischemia (at rest /on noninvasive stress test)

Revasularization

Hi h i k li i l


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High risk clinical events

Recurrent angina/ischemia at restwith low-level activities despite

intensive medical therapy

Elevated cardiac TnT or TnI

New/presumably new ST-

segment depression

Signs/symptoms of heart failure

or new/worsening mitral

regurgitation

High-risk findings from

noninvasive testing

Hemodynamic instability

Sustained ventricular tachycardia

PCI within 6 months

Prior CABG

High risk score (e.g., TIMI,GRACE)

- LVEF < 40%)


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Meta-analysis of the benefit of a routine invasive versus selective invasive (i.e.,

conservative) strategy for patients with unstable angina or NSTEMI on the rate of

death, myocardial infarction, or rehospitalisation through follow-up.

J Am Coll Cardiol 2006; 48:1319.


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Medical therapy BMS group DES group

ASA 75-162

mg/d indefinitely

&

Clopidogrel 75

mg/d for at least1 month and

ideally up to 1

year

ASA 162-325 mg/d

(1 month)

75-162 mg/d

(indefinitely)

&

Clopidogrel 75

mg/d or Prasugrel

10 mg/d (for at

least 1 year)

ASA 162-325 mg/d

(SES-3months)

(PES-6months)

75-162 mg/d

(indefinitely)&

Clopidogrel 75 mg/d

Or

prasugrel 10mg for

at least 1 year

Long term Antiplatelet therapy

Class I


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Lipid Management

Lipid management should include assessment of a fasting lipid

profile for all patients, within 24 h of hospitalization.

High dose statins in the absence of contraindications, regardless

of baseline LDL-C and diet modification, should be given topost-UA/NSTEMI patients, including post revascularization

patients.

LDL goal:


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Meta analysis of intensive v/s standard statin therapy, showing a highly

significant 16% reduction in the risk of coronary death or MI

(p


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The benefit of intensive statin therapy initiated early after acute coronary

syndrome (ACS) in the PROVE ITTIMI 22 trial. A significant reduction in

events is seen in the first 30 days.

J Am Coll Cardiol 46:1405, 2005.)

Patients with UA/NSTEMI

summary


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Patients with UA/NSTEMI

Aspirin, clopidogrel, UFH/enoxaparin,

beta blocker, nitrates.

High risk

+Troponin, STs,TIMI score3

Recurrent Ischemia, CHF,

Prior Revascularization

Low risk

Normal ECGNegative Markers

TIMI score 0- 2

GpIIb/IIIa inhibitor

Conservative strategyInvasive strategy

summary


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Hope you are not confused !

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