1

CURRICULUM VITAE

SALLY AMAN NASUTION, MD, FINASIM, FACP

- Born in Medan, 8th August 1967
- Internist – Cardiologist
- Faculty Member Division of Cardiology, Department
of Internal Medicine at Faculty of Medicine Universitas
Indonesia, Jakarta
- Head of Intensive Coronary Care Unit (ICCU),
Integrated Cardiac Services Cipto Mangunkusumo
National General Hospital Jakarta
- President of the Indonesian Society of Internal
Medicine
ACS Management :
From Guidelines into
Practice

Dr dr SALLY AMAN NASUTION, SpPD-KKV, FINASIM,

FACP
Division of Cardiology Department of Internal Medicine
Faculty of Medicine Universitas Indonesia
Cipto Mangunkusumo National General Hospital
Jakarta
Acute Coronary Syndrome (ACS)

Acute thrombosis induced by a ruptured or eroded

atherosclerotic coronary plaque, with or without
concomitant vasoconstriction, causing a sudden and
critical reduction in blood flow

3 Bentzon JF et al. Circ Res. 2014;114:1852-1866

Atherosclerosis
Stable Angina vs Unstable Angina
Initial Assessment Suspected ACS
Clinical Presentation
Prolonged (>20 min) anginal pain at rest;
New onset (de novo) angina (Class II or III) of the
Classification of the Canadian Cardiovascular
Society;
Recent destabilization of previously stable angina
with at least Canadian Cardiovascular Society
Class III angina characteristics (crescendo
angina); or
Post-MI angina.
Bassand JP et al. European Heart Journal. 2007; 28: 1598–1660
Chest Pain evaluation - SOCRATES
S Site
central (retrosternal)
location
O Onset sudden or acute onset
C Character
heavy or burning
sensation with
R Radiation radiation to the arm or jaw
A Association
associated dyspnoea,
nausea or sweating
T Time duration >15 minutes
E Exacerbating/relievi relief of symptoms by
ng factor nitrates
S Severity
worsening of symptoms
by activity
Pandie S et al. S Afr Med J 2016;106(3):239-245.

ECG in STEMI
In the absence of LVH and LBBB
New ST elevation at the J point in 2
contiguous leads with ≥0.2 mV in men
(>40 years old) or ≥ 0.15 mV in women in
leads V2-V3 and/or ≥0.1 mV in other leads
9
In the presence LBBB or ST depression
• New LBBB, and symptoms suggestive of ACS
• ST depression in leads V1–V3 indicate
inferobasal myocardial ischemia (especially
when the terminal T-wave is positive)

In suspected posterior (circumflex artery- related)

or right ventricle-related infarction

• ST elevation in V7,V8 and V9 using a cut-point

>0.05 mV.
• ST elevation in V3R and V4R, using a cut-off point
>0.05 mV, and >0.1 mV in men <30 years.
ST Segment Elevation LBBB

Steg G et al. Eur Heart J. 2012;33:2569-619

ECG Changes of Injury Acute 10

Myocardial Infarction
In early stage of AMI , ECG may be
normal or near normal

5- 30 min after onset of

infarction

Changes
< 1 mm - > 10 mm

1-2 hours of onset

symptoms

• ST resolves - anterior up to 2
weeks; posterior > 2 weeks
• T wave : many months

Morris F, Brady WJ. BMJ 2002 Apr 6;;324(7341) :831-4

ECG in NSTEACS
• Normal ECG in more than 1/3 of patients
• Abnormalities
• ST Depresssion
• Transient ST Elevation
• T-Wave changes

Flattening of Horizontal
ST Segment ST Segment

Making T wave Downsloping

more obviouS ST segment
Roffi M et al. Eur Heart J 2016;37(3):267-315 ; Channer K, Morris F. BMJ 2002;324:1023–6 /
 12
Cardiac BioMarker

Kumar A; Cannon CP et al. Mayo Clin Proc. 2009;84(10):917-938; Steg G et al. Eur Heart J. 2012;33:2569-619;
Roffi M et al. European Heart Journal. 2016; 37: 267–315
 STEMI Care
the Right Reperfusion
Strategy
2017

A primary PCI strategy is

recommended over fibrinolysis
within indicated Timeframes
1A
Ibanez B et al. Eur Heart J 2017. https://academic.oup.com/eurheartj/article/4095042
 Recommended / Should be Not recommended
indicated considered

Ibanez B et al. Eur Heart J 2017. https://academic.oup.com/eurheartj/article/4095042

 Recommended / Should be Not recommended
indicated considered
Ibanez B et al. Eur Heart J 2017. https://academic.oup.com/eurheartj/article/4095042
Contraindications to fibrinolytic therapy1–3

ABSOLUTE RELATIVE

• Previous intracranial hemorrhage or stroke of • Transient ischemic attack in the preceding 6

unknown origin at any time month
• Ischemic stroke in the preceding 6 months • Oral anticoagulant therapy
• Central nervous system damage or neoplasms or • Pregnancy or within 1 week postpartum
arteriovenous malformation • Refractory hypertension
• Recent major trauma/surgery/head injury (within • Advanced liver disease
the preceding 3 weeks) • Infective endocarditis
• Gastrointestinal bleeding within the past mo • Active peptic ulcer
• Known bleeding disorder (excluding menses) • Prolonged or traumatic resuscitation
• Aortic dissection
• Non-compressible punctures in the past 24 h
(e.g. liver biopsy, lumbar puncture)
• Ischemic stroke more than 6 months ago

1. Ibanez B et al. Eur Heart J 2017. https://academic.oup.com/eurheartj/article/4095042; Accessed November 6, 2017; 2. O’Gara PT et al. Circulation 2013;127:e362–e425; 3.
Morse MA et al. Drugs 009;69:1945–1966
20

Preparation Fibrinolytic therapy

1. Prepare Patients (Provide informed concent )
2. Drug and Equipment preparation

Streptokinase 1.5 jt Trolley Emergency Defibrilator Monitor ECG

unit

3. Administered Drug
• IV line – 2 ways if hemodynamic is not stabil
• Disolve streptokinase with NaCL / RL 100 ml
• Infused for 30 – 60 minutes

4. Monitoring every 10 minutes

Vital check, Symptoms, Heart Rhythm

Reference : iSTEMI Indonesia Video

 Fibrinolytic Complication
Hypotention Allergic reaction Bleeding Arythmia
• Patient position – Mild allergic Minor Bleeding • Refer to ACLS
supine Antihistamin injection Pressure to bleeding guidelines
• Reduce or stop (difenhidramin 10 mg area
streptokinase drops i.v) Major Bleeding – eg • Reperfusion sign
• Provide Ringer Severe allergic ICH • Premature
Lactate / NaCL 100 Dexamethasone Stop streptokinase and Ventricular
ml (10 minutes) injection 5 mg refer patient for further Contraction
• Stop vasodilator bleeding management • Idiophatic
drug (eg. Nitrate) Ventricular Rhytm
• Streptokinase drop
continue if systolic
pressure > 90
mmHg
Parameter Successful Fibrinolytic Therapy

1. Reduction of chest pain

2. Decrease ST elevation > 50%
3. Arrhythmia reperfusion
Reference : iSTEMI Indonesia Video
 Summary
• Reperfusion is a key strategy in Acute STEMI care and it’s time
dependent
• PPCI is preferred options for reperfusion strategy for STEMI
patients
• Fibrinolytic therapy is an important reperfusion alternative
when onset chest pain < 3 hours or when primary PCI cannot
be offered in a timely manner
• Important to know capabilities of each hospital before
referring STEMI patients to prevent delay

22
 NSTEACS Management :
The importance of Risk Stratification
 Management strategy

Step 1. initial evaluation

Step 2. Diagnosis validation, risk assessment and

rhythm monitoring

Step 3. invasive strategy

Step 4. revascularization modalities

Step 5. hospital discharge

and post-discharge management

Roffi M et al. European Heart Journal 2015. doi:10.1093/eurheartj/ehv320 24

 Risk Stratification is important in NSTEACS Management

1 CLINICAL CONDITION

2 3
TIMI SCORE GRACE SCORE

Less accurate in predicting events but its recommended as the preferred

simplicity makes it useful and widely classification to apply on admission and
accepted at discharge in daily clinical routine
practice

Hamm W et al. European Heart Journal (2007) 28, 1598–1660; Hamm CW et al. Eur Heart J 2011;32:2999 – 3054
GRACE SCORE
Predictor Score Predictor Score Predictor Score
Age, years Systolic Blood Pressure (mmHg) Killip class
< 40 0 < 80 63 I 0
40 - 49 18 80 – 99 58 II 21
50 - 59 36 100 - 119 47 III 43
60 - 69 55 120 - 139 37 IV 64
70 - 79 73 140 - 159 26
Predictor Score
80 91 160 - 199 11
Cardiac arrest 43
> 200 0 at admission

Predictor Score Predictor Score Elevated 15

Heart Rate , beats/min cardiac
Creatinine (µmol/L)
markers
< 70 0 0 - 34 2
ST Segment 30
70-89 7 35 – 70 5 deviation
90-109 13 71 – 105 8
110 - 149 23 106 – 140 11 Risk category GRACE In-hospital
150 - 199 36 141 – 176 14 (tertile) Risk Score death
(%)
> 200 46 177 – 353 23
Low ≤ 108 <1
≥ 354 31
Intermediate 109 - 140 1-3

Khalill R et al. Exp Clin Cardiol.2009; 14(2): e25 – e30 High > 140 >3
29

Cath lab or later ?

Benefit of early intervention in high risk patients

Kaplan–Meier Cumulative Risk of the Primary Outcome (death, myocardial infarction, or stroke), Stratified
According to GRACE Risk Score at Baseline.
Mehta, SR et al. N Engl J Med 2009;360:2165-75.
 CRUSADE SCORE
Predictor Score Predictor Score Predictor Score
Hematokrit (%) Frekwensi nadi , x / menit Prior Vascular Disease
<31 9 ≤ 70 9 No 0
31-33.9 7 71-80 7 Yes 6
34 – 36.9 3 81 – 90 3 Diabetes Mellitus
37 – 39.9 2 91 - 100 2 No 0
≥ 40 0 101 - 110 0 Yes 6
Creatinine Clearance, ml/min 111 - 120 10 Systolic Blood Pressure at
≥ 121 11 admission
≤ 15 39 ≤ 90 10
Sex
> 15 - 30 35 91 - 100 8
Male 0
> 30 - 60 28 101 - 120 5
Female 8
> 60 - 90 17 121 - 180 1
Sign of CHF at admission
> 90 - 120 7 181 - 200 3
No 0
>120 0 ≥ 201 5
Yes 7
Very low (bleeding score 20); low (bleeding score 21 to 30); moderate (bleeding score 31 to 40); high (bleeding score 41 to 50): and very
high (bleeding score 50)
Subherwal S et al. Circulation. 2009;119:1873-1882
Choosing the right
Antiplatelet in ACS
 Initial Treatment when an ACS diagnosis appears likely based
on ESC NSTEACS Guideline1,2

Aspirin Initial dose of 150 – 300 mg non-enteric formulation followed by 75-100

mg/day (I.v. administration is acceptable)

P2Y12 inhibitor Loading dose of ticagrelor or clopidogrel

Anticoagulation Choice between different options depends on strategy:

• Fondaparinux 2.5 mg/daily subcutaneously
• Enoxaparin 1 mg/kg twice daily subcutaneously
• UHF Lv. Bolus 60-70 IU/kg (maximum 5000 IU) followed by infusion of 12-
15 IU/kg/h (maximum 1000 IU/h) titrated to aPTT 1.5 – 2.5 × control
• Bivalirudin is indicated only in patients with a planned invasive strategy

Oral β-Blocker If tachycardic or hypertensive without signs of heart failure

P2Y12 inhibitor is recommended in initiation soon after the diagnosis of NSTE-

ACS irrespective of management strategy2

32 Reference: 1. Hamm CW et al. Eur Heart J. 2011; 32:2999-30354; 2. Roffi M et al. Eur Heart J 2016;37(3):267-315
PLATELET Plays Important Role in
Thrombus Formation

Schafer AL. Am j Med.1996;101(2):199-209

 Aspirin

Thienopyridine
• Ticlopidine
• Clopidogrel
• Prasugrel

Reversible
P2Y12
inhibitors
• Ticagrelor
• Cangrelor
GPIIb/Iia Antagonists • Elinogrel

Angiolillo DJ. Drugs. 2012 Nov 12;72(16):2087-116

34
 Antiplatelet recommendation in Updated ACS
Guidelines

Aspirin should be given to all patients without

contraindications at an initial loading dose of 150–300 mg,
and at a maintenance dose of 75–100 mg daily long-term
regardless of treatment strategy.

A P2Y12 inhibitor should be added to aspirin as soon as

possible and maintained over 12 months, unless there are
contraindications such as excessive risk of bleeding.

Clopidogrel Ticagrelor Prasugrel*

1. Roffi M et al. Eur Heart J 2016;37(3):267-315;2.Ibanez B et al. European *Not yet approved and
Heart Journal (2017) 00, 1–66 available in Indonesia
35
 Profile P2Y12 inhibitor

Profil Clopidogrel Ticagrelor

Class Thienopyridine Triazolopyrimidine

Binding with Irreversible Reversible

receptor

Drug metabolism Pro drug Active drug

Adapted from Hamm CW et al. Eur Heart J 2011;32:2999 – 3054

 CYP2C19 Polymorphisms

Ultrarapid Extensive Intermediate Poor

metabolizer Metabolizer Metabolizer Metabolizer

Normal or Normal enzyme Intermediate Low or absent

increased activity. enzyme activity. enzyme activity
enzyme activity.

Reduced response of “pro drug” agent

± 2 % in Caucasian ± 4 % of african ±14% of Asian

Sukasem C et al. Pharmacogenomics and Personalized Medicine 2013:6 85–91

 DISPERSE Trial: Ticagrelor has Greater and More
Consistent IPA vs. Clopidogrel1

Clopidogrel 75 mg od Ticagrelor 100 mg bd

100 100

80 80

60 DAY 1 60

40 40

Mean IPA, %
Mean IPA, %

20 20

0 0
0 2 4 8 12 0 2 4 8 12

100 100

80 80

60 60

40
DAY 14 40

20 20
 2nd dose
0 0
0 2 4 8 12 24 0 2 4 8 12 24

Time, h Time, h

IPA = inhibition of platelet aggregation; od = once daily; bd = twice daily.

Reference: 1. Adapted from Husted SE, et al. Presented at: European Society of Cardiology Annual Congress 2005; 3-7
September, 2005; Stockholm, Sweden.
 Onset P2Y12 inhibitor
Ticagrelor provide Faster Onset and offset vs high dose
clopidogrel Last maintenance dose
Loading At 2 hours TICA 90 mg bid
100 Ticagrelor (n=54)
Dose
90
* 88%
* *ticagrelor * * †
TICA 180 mg
* Vs.* Clopidogrel (n=50)
80 38% clopidogrel * * P<0,0001
70 † P<0,005
‡ P<0,05
60 At 30 minutes
IPA %

50 41%
* ticagrelor
Vs.
40 CLOPI 75 mg qd
8% clopidogrel ‡
30
†
Catatan : penelitian ini dilakukan pada pasien CAD yang
20 mengkonsumsi aspirin tanpa riwayat ACS <1 tahun
Ticagrelor belum mendapatkan persetujuan untuk
10 populasi pasien ini.
CLO 600 mg
0

0 0.5 1 2 4 8 24 6 weeks 0 2 4 8 24 48 72 120 168 240

Onset Maintenance Offset

40
Time (hours)) Time (hours)
8
Referensi Adapted from Gurbel PA, et al. Circulation. 2009;120:2577–2585. IPA : Inhibition of Platelet Aggregation
 PLATO Study

PLATO study tested the hypothesis that…

ticagrelor will result in a lower risk of recurrent thrombotic events in a broad
patient population with ACS as compared to clopidogrel and this would be
achieved with a clinically acceptable bleeding rate and overall safety profile

PLATO Study:
• 43 countries
• 862 sites 18,624
43862
countries
patients
sites
• 18,624 patients

STEMI Primary PCI NSTEACS Invasive NSTEACS Non invasive

  
Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.
 Benefit CV Mortality P2Y12 Inhibitor

CURE1 TRITON TIMI 382 PLATO3

P = N/A P = NS P = 0.001
(%)death (%)

5.50
5.10 5.10
CV deathCV

4.00
Rateofofcomposite

2.40
2.10
Rate

Plasebo Clopidogrel Clopidogrel Prasugrel * Clopidogrel Ticagrelor

n = 12.562 n = 13.608 n = 18.624

NNT = 250 NNT = 333 NNT = 91

1.Yusuf S et al. N Engl J Med 2001;345; 2.Wiviott SD e tal. N Engl J Med 2007;357:2001-15; 3.Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.
* Prasugrel is not yet approved and available in Indonesia
ESC STEMI 2017 : Ticagrelor is preferred OAP before
clopidogrel – STEMI undergoing Primary PCI
 ESC NSTEACS 2015:
Ticagrelor is preferred OAP for NSTEACS

A P2Y12 inhibitor is recommended, in addition to aspirin, for 12 months

unless there are contraindications such as excessive risk of bleeds. 1A
Ticagrelor is recommended, in the absence of
contraindications,
for all patients at moderate-to-high risk of ischaemic events
(e.g. elevated cardiac troponins), regardless of initial treatment 1B
strategy and including those pretreated with clopidogrel
(which should be discontinued when ticagrelor is started).

Prasugrel is recommended in patients who are proceeding to PCI if

no contraindication). 1B

Clopidogrel is recommended for patients who cannot receive

ticagrelor or prasugrel or who require oral anticoagulation. 1B

44 Roffi M et al. Eur Heart J 2016;37(3):267-315

 TICAGRELOR versus CLOPIDOGREL AFTER
THROMBOLYTIC THERAPY IN PATIENTS
WITH STEMI : RANDOMIZED CLINICAL TRIAL

Otavio Berwanger, MD, PhD

 Ticagrelor 90 mg did not increase TIMI major
bleeding at 30 days compared with clopidogrel 1,2
< 75 years old

Ticagrelor
2.5
Cumulative incidence of primary outcome,

Clopidogrel
2
TIMI major bleeding (KM%)

1.5
1
0.5
P value non inferiority <0.001
0
0 3 6 9 12 15 18 21 24 27 30
Time (days)

1. Berwanger O et al. JAMA Cardiol 2018 doi:10.1001/jamacardio.2018.0612; 2. Berwanger O et al. JAMA Cardiol 2018
doi:10.1001/jamacardio.2018.0612 Supplementary Appendix
 ESC Guidelines 2017 :
Adjunctive antiplatelet therapy to support reperfusion with fibrinolytic
therapy1,2

Recommendations Class LOE

Oral or IV ASA is indicated I B
Clopidogrel is indicated in addition to ASA (300 mg
loading dose in patients aged ≤75, 75 mg daily dose)
I A
DAPT (in the form of ASA + P2Y12 inhibitor*) is indicated
for up to 1 year in patients undergoing fibrinolysis and
subsequent PCI. I C

*Clopidogrel is the P2Y12 inhibitor of choice as co-adjuvant and after

fibrinolysis, but 48 hours after fibrinolysis, switch to prasugrel/ticagrelor
may be considered in patients who underwent PCI

1. Ibanez B et al. European Heart Journal (2017) 00, 1–66; 2. Valgimigli, et al. European Heart Journal (2017) 0, 1–48
 Identify patients for more potent
DAPT
CRUSADE score

GRACE score
Very high > 50

High risk: Score >140

In-hospital death: >3%
High = 41 – 50

Bleeding Risk
Moderate = 31 – 40
Intermediate risk: 109 – 140
In-hospital death: 1-3 %

Low = 21 – 30
Ischemic Risk

Low risk: Score ≤ 108

In-hospital death: <1% Very low <= 20

How you treat this patients?

Referensi: Valgimigli M et al. European Heart Journal 2017; 0; 1–48

 PPI treatment algorithm in ACS patients

49
Agewall S et al. European Heart Journal (2013) 34, 1708–1715
ESC 2017 Focused Update DAPT in CAD : 50

Algorithm for switching between oral P2Y12

inhibitors in ACUTE setting 1

Class I LOE B
Class Iib LOE C

Switch from Clopidogrel to Ticagrelor in Acute Setting is allowed

irrespective of prior clopidogrel timing and dosing (1B)
Reference: 1. Valgimigli M et al. European Heart Journal (2017) 0, 1–48
ESC 2017 Focused Update DAPT in CAD : 51
Algorithm for switching between oral P2Y12 inhibitors
in CHRONIC setting 1

• Swith after 24 hr last

dose
• Clopidogrel to
ticagrelor ~ no
loading dose
• Ticagrelor to
clopidogrel ~ load
600 mg clopidogrel

Class IIb LOE C

Additional switching between oral P2Y12 inhibitors may be considered in

cases of side effects/drug intolerance according to the proposed algorithms.
Reference: 1. Valgimigli M et al. European Heart Journal (2017) 0, 1–48
 Antiplatelet based on ACS Diagnosis 52

Acute coronary syndrome

UA / NSTEMI STEMI

Medical PCI Fibrinolytic PCI

Management
• Ticagrelor • Clopidogrel • Ticagrelor
• Ticagrelor • Prasugrel* • Switch to • Prasugrel*
• Clopidogrel • Clopidogrel ticagrelor – • Clopidogrel
Post
thrombolytic
PCI

* Prasugrel is not yet approved and available in Indonesia

Roffi M et al. European Heart Journal. 2016; 37, 267–315; Steg PG et al. Eur Heart J 2012;33:2569–2619
 Antiplatelet dosage
Antiplatelet Dosis loading Dosis Lama
maintenance Pengobatan
Aspirin 325 mg 75 – 100 mg Indefinitely
Clopidogrel
PCI 600 mg 75 mg (satu kali 12 bulan
sehari)
Medically 300 mg 75 mg (satu kali 12 bulan
Managed sehari)
Ticagrelor
PCI
Post Fibrinolytic 90 mg (dua kali 12 bulan
180 mg
Medically sehari)
Managed

53 • Steg PG et al. Eur Heart J 2012;33:2569–2619; 3.Hamm CW et al. Eur Heart J 2011;32:2999 – 3054
Optimizing ACS Management in Referral Hospital

 STEMI
 Identify symptom onset
 choose the right reperfusion strategy
 Do it as early as possible

 NSTEACS
 Do not underestimated the risk
 Do risk stratification
 Refer for invasive for High Risk Patients

 Do initial treatment including choosing the right antiplatelet for ACS

 Ticagrelor is recommended as preferred OAP by International

Guidelines for STEMI Primary PCI and NSTEACS

 Ticagrelor can be considered in post fibrinolytic patients undergoing

PCI
Lombok Beach, Indonesia, 2017