Acute Coronary Syndrome

Current Guidelines and Management

Dr. Emanoel Oepangat SpJP, FIHA, FAPSIC

‘Emergencies in Cardiovascular Disease’

Siloam TB Simatupang, 29 Sept 2018
Definition and Pathophysiology
 Acute Coronary Syndrome
• ACS has evolved as a useful operational term
that refers to a spectrum of conditions
compatible with acute myocardial ischemia
and/or infarction that are usually due to an
abrupt reduction in coronary blood flow

2014 AHA/ACC Guideline for the Management of Patients With

Non–ST-Elevation Acute Coronary Syndromes
 Acute Coronary Syndrome
• ACS is characterized by an imbalance between
myocardial oxygen supply and demand.
• Inflammation and/or infection may weaken the
structure of the fibrous cap that overlies the
atherosclerotic plaque.
• Rupture or erosion of an atherosclerotic plaque
exposes the lipid-rich, thrombogenic contents of
the plaque to the blood.
• initiation of a complex cascade of events that
culminates in the formation of occlusive or
nonocclusive thrombus.
Bertrand ME, Simoons ML, Fox KAA, et al. Management of acute coronary syndromes in
patients presenting without persistent ST-segment elevation. Eur Heart J. 2002;23:1809-
1840.
 Structure of thrombus
following plaque disruption
UA/NSTEMI STEMI
Non-occlusive thrombus Occlusive thrombus
(platelets, some fibrins) (platelets, fibrins, red cell)

Plaque core

Intra-plaque thrombus
(platelet dominated)
 Spectrum of CAD/ACS
No ST elevation ST elevation
Stable Unstable NSTEMI STEMI
angina angina

ACUTE CORONARY SYNDROMES

CAD = coronary artery disease; NSTEMI = non-ST-segment elevation myocardial infarction;

STEMI = ST-segment elevation myocardial infarction.
Source (Photos): Davies MJ. Heart. 2000;83:361-366.
 Definition of ACS
Inflammation and/or infection, plaque rupture, thrombosis,
endothelial dysfunction, and/or vasoconstriction

ACS

No ST-segment elevation STEMI

NSTEMI

Unstable angina (UA)

Myocardial infarction (MI)

Treatment options: NQMI QwMI

anti-ischemic agents, antithrombin therapy,
antiplatelet agents,
fibrinolytic treatment, Treatment options:
coronary revascularization, lipid-lowering therapy, rapid recanalization by fibrinolytic treatment or
ACE inhibitors primary angioplasty

STEMI=ST-segment elevation MI; NSTEMI=non-ST-segment MI; NQMI=non-Q–wave MI; QwMI=Q–wave MI; ACE=angiotensin-converting enzyme.

Bertrand ME et al. Eur Heart J. 2002;23:1809-1840; Braunwald E et al. ACC/AHA Task Force on Practice Guidelines. 2002.
 Men and Women With ACS Are at High Risk of Early
Mortality

30-day mortality in men and women with ACS

10.0

8.0
Cumulative mortality (% )

6.0

4.0

2.0 Women (n=546)

Men (n=1198)
0.0
0 5 10 15 20 25 30
Days after admission to CCU
CCU=coronary care unit.

Adapted from Perers E et al. Int J Cardiol. 2005;103:120-127.

Clinical Assesment
 Chest pain
Assess 12 assesment
Initial lead ECG Goal = 10 min
– Hx
– PE
– EKG and EKG monitoring
– CXR
Non Chronic Possible Definite
Cardiac Stable ACS ACS
Diagnosis Angina
 Fig 2 Admission decisions with acute chest pain.

Adam Timmis BMJ 2015;351:bmj.h5153

©2015 by British Medical Journal Publishing Group

 Acute Coronary Syndromes

ST-elevation MI

Cardiac marker +ve Non-ST elevation ACS Unstable angina

Cardiac marker +ve Cardiac marker - ve

 0 h/3 h rule-out algorithm of non-ST-elevation acute coronary syndromes using high-
sensitivity cardiac troponin assays.

Authors/Task Force Members et al. Eur Heart J

2015;eurheartj.ehv320

© The European Society of Cardiology 2015. All rights reserved. For permissions please email:
journals.permissions@oup.com.
Initial Strategy
 Initial assessment of patients with suspected acute coronary syndromes.

Authors/Task Force Members et al. Eur Heart J

2015;eurheartj.ehv320

© The European Society of Cardiology 2015. All rights reserved. For permissions please email:
journals.permissions@oup.com.
Early Hospital Care In ACS
STEMI
 2013 ACCF/AHA Guideline for the
Management of ST-Elevation Myocardial
Infarction

Developed in Collaboration with American College of Emergency Physicians

and Society for Cardiovascular Angiography and Interventions

© American College of Cardiology Foundation and American Heart Association, Inc.

NSTEMI
 2014 AHA/ACC Guideline
for the Management of Patients With Non–
ST-Elevation Acute Coronary Syndromes:
Executive Summary

A Report of the American College of

Cardiology/American Heart Association Task
Force on Practice Guidelines

Circulation. published online September 23, 2014

Initial Conservative Strategy : Early Hospital Care
• ASA; clopidogrel if intolerant (I, A)
• Anticoagulant therapy should be added to
antiplatelet therapy as soon as possible after
presentation (I, A)
– Enoxaparin or UFH (I, A)
– Fondaparinux (I, B)
– Enoxaparin or fondaparinux preferable (IIa, B)
• Initiate clopidogrel/ticagrelor/prasugrel, loading
dose + maintenance dose (I, B)
ACC/AHA 2013 Guidelines for the Management of
Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
 Adjunctive Therapies
• Beta-blocker
– Start with low dose, ongoing ischaemic
symptoms and without contraindications.
• IV nitroglycerine
– recurrent ischemia, large anterior MI, heart
failure, antihypertensive effects
• ACE inhibitor
– large anterior wall MI, heart failure within 24.

ACC/AHA 2013 Guidelines for the Management of

Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
Antiplatelet/Anticoagulant therapy in
NSTEMI ACS
 Invasive Strategy
Invasive coronary angiography maintains its central role in the
management of patients with NSTE-ACS.
In the vast majority of cases it allows clinicians to
• confirm the diagnosis of ACS related to obstructive
epicardial CAD (or to rule out a coronary origin of chest
pain) and, as a consequence, to guide antithrombotic
treatment and avoid unnecessary exposure to
antithrombotic agents;
• identify the culprit lesion(s);
• establish the indication for coronary revascularization
and assess the suitability of coronary anatomy for PCI
and CABG and
• stratify the patient’s short- and long-term risk.
ESC Guidelines for NSTEMI-ACSCS ACC/ AHA Guidelines for NSTEMI-ACS
 Selection of non-ST-elevation acute coronary syndrome (NSTE-ACS) treatment strategy and
timing according to initial risk stratification.

Authors/Task Force Members et al. Eur Heart J

2015;eurheartj.ehv320

© The European Society of Cardiology 2015. All rights reserved. For permissions please email:
journals.permissions@oup.com.
Conclusion
 Management Strategies in Acute Coronary syndrome(ACS)

Symptoms of Acute Coronary Syndrome

ST elevation No ST elevation
(STEMI) (UA/NSTEMI)
EKG

Reperfusion approach All patients Antithrombotic approach

1. ASA
2. Heparin(UFH or LMWH)
3. Clopidogrel/Ticagrelor/
Prasugrel
4. Choose reperfusion method
a. Fibrinolytic drug
b. Primary PCI
1. Anti-ischemic medications
Beta-blocker
Nitrated
+/-Ca++ channel blocker
2. General measures
Oxygen
Pain control (morphine)
3. Additional therapies
ACE inhibitor
Statin
1. ASA
2. Heparin(UFH or LMWH)
3. Clopidogrel/Ticagrelor/
Prasugrel
4. For high risk patients
GP IIb/IIIa inhibitor
Proceed to cathlab
 Summary of Evidence

Study Subjects N Dose of Enox Efficacy Safety (enox vs UFH)

ATOLL 1 STEMI 910 0.5 mg/kg IV Similar primary endpoint Similar rate of major and minor bleeding
(primary PCI) (additional 0.25
– Enox vs UFH 41% RRR in the rate of the main secondary endpoint
mg/kg, if needed)
Reduced death, complication of myocardial infarction, or
major bleeding
Per protocol analysis : Enoxaparin resulted in significant
Per protocol analysis : Enoxaparin resulted in
improvement of the NET CLINICAL BENEFIT (RR 0.46;
less major bleeding (RR 0.46; p=0.050)
p=0.0002)
ExTRACT- STEMI 20,506 30 mg IV –> 1.0 17% RRR in the primary endpoint Higher rate of major bleeding (2.1 vs 1.4%;
TIMI 25 2 (Thrombolysis mg/kg SC q12h p<0.001)
) – Enox vs 33% RRR in non-fatal re-infarction
UFH ≥ 75 yo : 0.75 mg/kg Similar rate of intracranial hemorrhage
Reduced in the composite of death, nonfatal
q12h
reinfarction, or nonfatal intracranial hemorrhage (10.1
vs 12.2%,p<0.001)
SYNERGY 3 NSTEMI 10,027 1 mg/kg q12h SC Similar primary endpoint Higher rate of TIMI major bleeding (9.1 vs
(PCI) – Enox 7.6%; p=0.008)
vs UFH Non-significant GUSTO severe bleeding
Subpopulation receiving consistent therapy : 18% Subpopulation receiving consistent therapy :
significant relative risk reduction in death or nonfatal MI increased GUSTO severe bleeding with enox vs
with enox UFH (2.9% vs. 2.1%, p 0.0465).
TIMI 11b – NSTEMI – 3,910 + 1 mg/kg q12h SC ≈ 20% RRR in the composite triple end point (death, MI Similar rate of major bleeding
ESSENCE 4 Enox vs UFH 3,171 or recurrent
Higher minor bleeding
Angina)
At 1 yr FU, 13% RRR in the composite triple end point

1. Montalescot G, et al.Lancet.2011;378:693-703; 2. Antman EM, et al.N Eng J Med.2006;354:1477-88. 3. SYNERGY Trial Investigators.JAMA.2004;292:45-54. 4. Antmant EM, et al.Circulation.1999;1602-8.
 Balance between antiplatelet effect and bleeding risk

“Use of more potent P2Y12 inhibitors (ticagrelor or prasugrel) in place of

clopidogrel also results in decreased ischemic risk and increased bleeding
risk” – Levine GN, et al 2016 ACC/AHA Guideline
 TOPIC: RCT study design

Design Interventions Primary endpoint

Prospective, randomized trial in 646 • Prasugrel or ticagrelor Death, non-fatal MI, stroke, all BARC bleedings at 12
ACS patients • Clopidogrel months

De-escalation DAPT group

1- year follow-up
Clopidogrel + aspirin FDC

• 646 ACS patients

undergoing PCI Composite primary endpoint
• Death, non fatal MI, stroke, all BARC bleeding
• Without ischemic events or
Randomization Secondary endpoints
bleeding (BARC ≥2) at
1:1 • Components of primary endpoint
1-month follow-up after PCI • Death, MI, stroke, BARC bleeding ≥2
• Receiving DAPT with a new
P2Y12 inhibitor + aspirin
Unchanged DAPT group
1- year follow-up
New P2Y12 inhibitor + aspirin

• TOPIC evaluated the effect of de-escalation from a new P2Y12 inhibitor to clopidogrel on clinical outcomes and results were reported at EuroPCR in May 2017 and simultaneously published in the European Heart Journal

TOPIC: Timing Of Platelet Inhibition after acute Coronary Syndrome

FDC, fixed-dose combination; NCT02099422
Cuisset T et al. Eur Heart J. 2017 May 16. doi: 10.1093/eurheartj/ehx175. [Epub ahead of print]

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 Conclusion

In patients without adverse event 1 month after stented

ACS, a switched DAPT is superior to an unchanged DAPT
strategy to prevent bleedings without increased risk of
ischemic events
 “ABCDE”
A- antiplatelets, ACE-I
B- beta-blocker, blood pressure control
C- cholesterol lowering, cigarette
smoking cessation
D- diet, diabetes management
E- exercise
TERIMAKASIH