UPDATE ON STEMI

MANAGEMENT

dr. Adi Purnawarman, Sp.JP(K)-FIHA.,FAsCC

Initial Assessment for ACS patients

10 minutes

No need to
wait the result
 Spectrum of Pathology and Clinical IHD

Stable angina NSTEMI STEMI

IHD= Ischaemic heart disease

ACS
NSTEMI= Non ST segment elevation myocardial infarction
STEMI= ST segment elevation acute myocardial infarction
ACS= Acute coronary syndrome

Adapted from Morrow DA, et al. N Engl J Med 2017;376:2053-64.

 Important To Identify Symptom Onset in STEMI
to choose the right reperfusion strategy

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

4
• Morris F, Brady WJ. BMJ 2002 Apr 6;;324(7341) :831-4
TIME and Myocardial Salvage
Component Time Delay

In Hospital and EMS

Diagnose capabilities

Improve Public
Awareness ACS Network
 Importance for Early Reperfusion

• Reperfusion is a key strategy in Acute STEMI care and it

time dependent
• Shortening the time from symptom to reperfusion and
choosing the optimal reperfusion strategy for STEMI
patients are a great challenges in practice.
• The infarction related artery (IRA) must be opened
early, consistently, and thoroughly in order to
effectively restore myocardial perfusion

1. Zhang et al. J Zhejiang Univ-Sci B (Biomed & Biotechnol). 2011; 12(8):629-632; 2. Ibanez B et al. Eur Heart J. 2017; 00: 1–66
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
indicated considered recommended

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

 Recommended / Should be Not
indicated considered recommended
Ibanez B et al. Eur Heart J 2017. https://academic.oup.com/eurheartj/article/4095042
 Timing and logistical factors influence choice of
reperfusion strategy

Time to reperfusion Healthcare resource

• Patient ability to recognize • PCI vs non-PCI capable hospitals1–3

symptoms1,2 • Dependence on operator
• Mode of transportation to the hospital expertise/volume3
(self-presentation vs EMS)1,2 • Availability of a 24/7 service1,3*
• Inter-hospital transfer challenges • Availability of a pre-hospital system for
(distance, traffic patterns, climatic diagnosis and treatment3,4,5
conditions etc)2,3
*Patients treated during non-working hours (6 PM to 8 AM) have
a greater delay to therapy, twice the failure rate of PPCI, and a
>2-fold increased 30-day mortality rate3,6

• 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. Armstrong PW et al.
Circulation 2009;119:1293–1303; 4. Welsh RC et al. Am Heart J 2006;152:1007–1014; 5. Danchin N et al. Circulation 2004;110:1909–1915; 6. Henriques JPS et al. J Am Coll Cardiol 2003;41:2138–2142
 Early Reperfusion Strategy in STEMI
Symptom Primary PCI Fibrinolytic
Onset
0 – 3 hours
 
3 – 12 hours
 
> 12 hours
 

Presented to PCI Routine

Hospital Angiography ± PCI
Maximum Wire crossing 60 Successful Thrombolytic
minutes Within 2-24 Hours
target
Presented to Non Rescue PCI
time from PCI Hospital If Failed Thrombolytic
diagnosis Wire crossing 90 (60 -90 min after start
minutes thrombolytic)

Ibanez B et al. Eur Heart J 2017. https://academic.oup.com/eurheartj/article/4095042. Accessed November 6, 2017.

 Mortality benefit with fibrinolytics is
greatest with shortest delay to treatment

Proportional effect of fibrinolytic therapy on

35-day mortality according to treatment delay1
22 trials were
reported between Time to Fibrinolytic Control/placebo
treatment (h) better better
1983 and 1993 and P=0.001 vs
0–1
indexed in the other
timepoints ≥1–2
MEDLINE
≥2–3
information
≥3–6
system.
≥6–12
≥12–24

0 0.5 1.0 40
Odds ratio
Benefit shown for treatment delays up to 12 hours

1. Boersma E et al. Lancet 1996;348:771–775;

 Langkah Pemberian Fibrinolytic Pada pasien
STEMI
Langkah 1 :
Nilai Waktu dan Risiko
• Onset (kurang dari 12 jam atau lebih dari 12 jam dengan tanda dan gejala
iskemik)
• Risiko fibrinolysis dan kontraindikasi fibrinolysis
• Waktu yang dibutuhkan untuk pemindahan ke pusat kesehatan yang mampu
melakukan IKP

Langkah 2 :
• Tentukan pilihan yang lebih baik , fibrinolysis atau strategy invasive

Langkah 3 :
• Bila sudah diputuskan fibrinolysis, harus segera diberikan di IGD untuk
minimalisir keterlambatan reperfusi
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
PERKI 2018:
Recommendations for Fibrinolytic Strategy
 ESC 2017 STEMI Guideline for
Fibrinolytic Therapy
19

Drug Initial Treatment

Dose of fibrinolytic therapy
Streptokinase 1.5 million units over 30-60 min i.v. Non-fibrin specific
Contraindication: Previous treatment with streptokinase & thrombolytics
anistreplase
Alteplase (tPA) 15 mg i.v. bolus Fibrin specific
0.75 mh/kg i.v. over 30 min (up to 50 mg) thrombolytics
Then 0.5 mg/kg i.v. over 60 min (up to 35 mg)
Reteplase (rPA) 10 units + 10 units i.v. bolus given 30 min apart Fibrin specific
thrombolytics
Tenecteplase Single i.v. bolus:
(TNK-tPA) 30 mg (6000 IU) if <60 kg
35 mg (7000 IU) if 60 to <70 kg Fibrin specific
40 mg (8000 IU) if 70 to <80 kg thrombolytics
45 mg (9000 IU) if 80 to <90 kg
50 mg (10000 IU) if ≥90 kg
It is recommended to reduce to half-dose in patients ≥ 75 years of
age

Ibanez B et al. European Heart Journal (2017) 00, 1–66

PERKI 2018:
Antithrombotic Recommendation
PERKI 2018 :
Interventions Following Fibrinolytic

Clopidogrel adalah penghambat P2Y12 yang dianjurkan untuk pasien yang

menjalani terapi fibrinolytic, namun jika pasien menjalani IKP setelah
fibrinolytic maka dapat dipertimbangkan menggantinya dengan ticagrelor
22

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 and it’s
management
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 i.v) Major Bleeding – eg • Reperfusion sign
drops Severe allergic ICH • Premature
• Provide Ringer Dexamethasone Stop streptokinase and Ventricular
Lactate / NaCL 100 injection 5 mg refer patient for further Contraction
ml (10 minutes) bleeding management • Idiophatic
• Stop vasodilator Ventricular
drug (eg. Nitrate) 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
 INITIAL TREATMENT
2018
Morphine
M sulfate iv
1-5 mg
• Can be repeated per 10 – 30 min, for
patient who not responsive

O O2 • when SaO2 < 90% or PaO < 60

N NTG / ISDN • If ongoing chest pain by the time admitted at ER

A ASPIRIN
Loading
Ticagrelor
or
•
•
180 mg loading dose + 90 mg BID
300 mg loading dose + 75 mg OD if
ticagrelor is not available or
160 – 320mg clopidogrel* contraindicated

• Pedoman Tatalaksana Sindroma Koroner Akut PERKI 2018 24

 Adjunctive treatment in Primary PCI and
Fibrinolytic Therapy
2018
Primary PCI Fibrinolytic

Antiplatelet • Ticagrelor 180 mg + 90 mg • Clopidogrel*

BID
• Clopidogrel 600 mg + 75 mg
OD if ticagrelor is not
available or contraindicated
Anticoagulant • UFH if patient can not
received bivalirudin or
enoxaparin
• Enoxaparin
GPIIbIIIa Only for no reflow or thrombotic
complication
* If patient undergoing PCI
after fibrinolytic may
considered to switch to
ticagrelor
• Enoxaparin sc
• UFH iv
• Fondaparinux bolus + sc for
24 hours - streptokinase

• Pedoman Tatalaksana Sindroma Koroner Akut PERKI 2018 25

 Profile P2Y12 inhibitor
Profil Clopidogrel Ticagrelor

Class Thienopyridine Triazolopyrimidine

Binding with receptor Irreversible Reversible

Drug metabolism Pro drug Active drug

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

 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

27 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 NSTEACS NSTEACS Non invasive

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

CURE1 TRITON PLATO3

TIMI 382
5.5 P = N/A 5.1 P = NS P = 0.001
(%)death (%)

0
0 5.10
CV deathCV

4.00
composite

2.40
ofof

2.10
Rate
Rate

Clopidogrel Prasugrel *
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
 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
TIMI major bleeding (KM%)

2
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
 TREAT trial : Safety By Time From Lysis

Berwanger O et al. JAMA Cardiol 2018 doi:10.1001/jamacardio.2018.0612 Supplementary Appendix 32

 Major Bleeding Events - 12 months
12 Ticagrelor Clopidogrel

10

8
%

P = 0.21 P = 0.43
4 P = 0.61
0.74 [0.46; 1.18] 0.82 [0.51; 1.33]
0.86 [0.47; 1.56] 2.12 1.96
2 1.57 1.62
1.05 1.22

0
TIMI Major Bleeding PLATO Major Bleeding BARC Type 3 - 5 Bleeding

P values and hazard ratios [95% CI] were calculated by Cox regression analysis.
 Pedoman Tatalaksana ACS PERKI 2018 :
Rekomendasi Terapi Fibrinolitik

Rekomendasi Kelas Level

Aspirin oral harus diberikan I B
Clopidogrel disarankan untuk diberikan bersamaan
dengan aspirin I A

DAPT (aspirin ditambah satu macam penghambat

P2Y12 inhibitor*) diindikasikan untuk 1 tahun pada I C
pasien yang menjalani fibrinolitik dilanjutkan IKP

*Clopidogrel adalah penghambat P2Y12 inhibitor yang

dianjurkan untuk pasien yang menjalani terapi fibrinolitik,
namun jika pasien menjalani IKP setelah fibrinolitik maka dapat
dipertimbangkan menggantinya dengan ticagrelor

PERKI. Buku Pedoman Tata Laksana Sindrom Koroner Akut. 2018 (IV)
 ESC 2017 Focused Update DAPT in CAD :
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 35
 Impact on Time Delays and 30-Day Mortality of the Number of Medical Parties
Involved Before Hospital Admission in the French FAST-MI Registry

0 or 1 Party 2 Parties ≥3 Parties

Median time from 100 (50–170) 122 (60–201) 155 (80–270)

first call to
reperfusion (range)

30-day mortality 5.5% 7.1% 12.1%

FAST-MI = French registry of Acute ST-segment elevation or non–ST-segment elevation Myocardial Infarction.

Danchin N. J Am Coll Cardiol Intv. 2009; 2: 901– 908.

 Recommendation System of Care in STEMI
based on Mission LIfeLine – AHA

Non-PCI Primary PCI

Hospital/ STEMI EMS Hospital/ STEMI-
Referring Center Receiving Center

• Registered with Mission Lifeline (one platform)

• Routine multidisciplinary team meeting
• Standardized protocol : Prehospital identification and
activation, destination protocol for STEMI receiving centre,
transfer protocol for STEMI referring Center
• Coordinator for recognized system, physician champion, EMS
medical director
• Accreditation for STEMI referring and receiving center

• http://www.heart.org/HEARTORG/Professional/MissionLifelineHomePage 37
 Summary
• Reperfusion is a key strategy in Acute STEMI care and it 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
• Ticagrelor is recommended antiplatelet for STEMI Primary PCI
and can be considered in post fibrinolytic patients undergoing
PCI

38