Dafsah Arifa Juzar

Cardiovascular Intensivist & Interventionist

Telephone: + 62 21 568 1111 ext. 1262/1265
Email: djuzar@gmail.com
Current position
• Head of Intensive Cardiovascular Care & Emergency Unit -
National Cardiovascular Center Harapan Kita, Jakarta, Indonesia
• Head of Critical Cardiovascular Care Division - Department
Cardiology & Vascular Medicine, School of Medicine University of
Indonesia, Jakarta, Indonesia
• Head coordinator iSTEMI initiatives
Education
• 2007- Cardiologist Department Cardiology & Vascular Medicine, -
School of Medicine University of Indonesia, Jakarta, Indonesia
• 2000 - Medical Doctor School of Medicine UNIKA Atma Jaya,
Jakarta, Indonesia
Fellowship
• Interventional Cardiology, Royal Perth Hospital, Perth-Australia 2011-2012
• Interventional Cardiology, National Cardiovascular Center Harapan Kita,
Jakarta 2010
• Acute and Intensive Cardiovascular Care, National Cardiovascular Center
Harapan Kita, Jakarta 2007 -2009
 Revascularization of AMI
in non PCI-Capable Health Services:
Pharmacology or Invasive Strategy ?
Dafsah Arifa Juzar
Intensive & Interventional Cardiologist

14 September 2018
Yogyakarta Cardiology Update
• Fibrinolysis
• Invasive Strategy
• Pharmaco-Invasive Strategy
 ATHEROSCLEROSIS:
from Plaque to ACS

Progression of coronary atherosclerosis results in plaque, which

ruptures, causing arterial thrombus that partially or completely occludes
the artery, leading to the clinical manifestations of ACS[Grech 2003:B]
Grech, ED. BMJ. 2003;326:1027-1030.
 ACS with persistent ACS without persistent
ST segment elevation ST segment elevation

Troponin Elevated Troponin Elevated or not

 Salvageable myocardium in STEMI: Time-dependent

TIME IS
MUSCLE!

Lama Oklusi

Becker LC, Ambrosio G: Myocardial consequences of reperfusion, Prog Cardiovasc Dis 30:23-
49, 1987
 Pasien normal dengan Nyeri Dada Revaskularisasi
faktor resiko

• Pasien dengan faktor • Nyeri dada kiri spesifik • Revaskularisasi cepat

resiko tinggi, Merokok, yang memberat dan • 15 menit untuk kembalikan
DM, HT, Hiperkolesterol, menjalar ke fungsi jantung
Riwayat keluarga Dll. lengan/Punggung • DTN 30’
• DTD 90’

Angio
koroner

Eko
Kardio
graf

Fungsi Ventrikel Kiri - Normal Fungsi ventrikel kiri – Fungsi Ventrikel Kiri - Normal
Lemah Gagal jantung
 Total In Hospital Mortality Rate
STEMI Patient Based on Reperfusion
iSTEMI West Jakarta + NCC-HK (3 Years)
16.0%
14.8% 14.8%
78 79
14.0% 13.2%
50% 64
12.0%

10.0%
61
Year 1
8.0% 7.4% Year 2
Year 3
6.0% 5.7%
43
4.2%
4.0% 26

2.0%
N=756 N= 624 N=822 N=567 N =484 N=532
0.0%
Reperfusion No Reperfusion

*36 Months Data, From 30 Juni 2014 – 30 juni 2017 in ISTEMI Network (West Jakarta)
 Metode reperfusi

Fibrinolisis Angioplast

• Streptokinase
• Alteplase
 Mortalitas STEMI
PPCI vs Fibrinolisis
Major Clinicla trial
35.0%
In hospital mortality 30- or 35-day mortality
30.0% 29.0%

25.0%
(739)

20.0%

15.0%

10.0% 8.7%
5.9%
5.0% (92)
(163)

(100
0.0% n=2767 n=1054 n=2545

PPCI Fibrinolysis
No Reperfusion
 Primary PCI :
Time to treatment and 1 year mortality

De Luca G et all. Circulation 2004:109:1223-1225

2018

LMD - Layanan Medis Darurat

KMP – Kontak Medis Pertama
IKP – Intervensi Koroner Perkutan KMP : Fasilitas IKP

Pedoman Tatalaksana Sindroma Koroner Akut PERKI 2018

 STEMI Standard of Care: iSTEMI Network
Spokes
Onset (FMC) Hub Reperfusion
1st Year DTD 104 min
120 min 155 min
DTN 80 min

330 min (5’ 30”)

2nd Year
150 min 120 min DTD 101 min
DTN 85 min

330 min (5’ 30”)

3rd Year
150 min 105 min DTD 115 min
DTN 75 min

275 min (4’ 35’’)

36 months data, 30 June 2014 – 30 July 2017 in iSTEMI Network (West Jakarta + NCCHK)
 METODA REPERFUSI BERDASARKAN
Rate reperfusi < 12 Jam FASKES
100% 120.00%
92% 90%
90% 100.00% 97%
81%
80%
80.00%
70% 67% 64% 62% 55%
60% 60.00%
45%
50% 40.00% 36% 38%

40% 20.00%
30% 2.3%
0.00%
20%
10%
0%
Harapn Kita RS Sanglah RS Iskak RSUD cengkareng
 Timing and logistical factors influence choice of
reperfusion strategy

Time to reperfusion Healthcare resource

• Patient ability to recognize symptoms1,2 • PCI vs non-PCI capable hospitals1–3

• Mode of transportation to the hospital • Dependence on operator
(self-presentation vs EMS)1,2 expertise/volume3
• Inter-hospital transfer challenges • Availability of a 24/7 service1,3*
(distance, traffic patterns, climatic • Availability of a pre-hospital system for
conditions etc)2,3 diagnosis and treatment3,4,5

*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
 Pharmacoinvasive
strategy
A strategy of initial pharmacologic/lytic reperfusion followed
by timely planned PCI between 3 and 24 hours

Early reperfusion therapy reduces the total ischemic time

 Higher TIMI flow grades (2 or 3)
 Better Clinical Outcomes
 GOAL OF THERAPY IN STEMI:
EARLY REPERFUSION
To open the blocked Infarct-Related Artery and Re-
establish coronary blood flow

Rapid Early Complete Sustained

PRIMARY PCI PHARMACO

INVASIVE
STRATEGY
Studies Comparing Early Routine PCI vs
Standard Therapy After Thrombolysis

Major
Majordriver
driverof
of
reduction
reductionwas
was
recurrent
recurrentischemia
ischemia

Halvorsen and Huber. Thromb Haemost 2011;

 METHODS
• Prospective study of 1892 patients with
STEMI
• Presented within 3 hours after symptom
onset and who were unable to undergo
primary PCI within 1 hour
• Randomly assigned to undergo either
primary PCI or fibrinolytic therapy (TNK)
• The primary end point was a composite of
death, shock, congestive heart failure, or re-
infarction up to 30 days.
 Median Times to Treatment
MEDIAN TIMES TO(min)
TREATMENT (min)
1st Medical Randomize IVRS
Sx onset contact
Rx TNK

62 29 9 100 min

1st Medical
78 min
Sx onset contact Randomize IVRS difference
Rx PPC

61 31 86
n=1892 1 Hour 2 Hours 178 min
F. Van de Werf, ACC 2013
 Median
MEDIAN Times
TIMES to Treatment
TO TREATMENT (min)
(min)
1st Medical Randomize IVRS
Sx onset contact
Rx TNK
36% Rescue PCI at 2.2h

62 29 9 100 min
64% non-urgent cath at 17h

1st Medical
Sx onset contact Randomize IVRS
Rx PPCI

61 31 86
=1892 1 Hour 2 Hours 178 min
F. Van de Werf, ACC 2013
 TIMI
TIMI FLOW RATESFLOW RATES

P<0.001 P=0.41

TIMI before PCI TIMI after PCI

F. Van de Werf, ACC 2013

INVASIVE PROCEDURES

Pharmaco Invasive - PPCI

Pharmaco-invasive PPCI P-value
(N=944) (N=948)
PCI performed 80% 90% <0.001

Stents deployed 96% 96% 0.95

CABG performed 4.7% 2.1% 0.002

GLE ENDPOINTS UP TO 30 DAYS
Single Endpoints upto 30
Days
Pharmaco-invasive PPCI P-value
(N=944) (N=948)

All cause death (43/939) 4.6% (42/946) 4.4% 0.88

Cardiac death (31/939) 3.3% (32/946) 3.4% 0.92

Congestive heart failure (57/939) 6.1% (72/943) 7.6% 0.18

Cardiogenic shock (41/939) 4.4% (56/944) 5.9% 0.13

Reinfarction (23/938) 2.5% (21/944) 2.2% 0.74

N-HOSPITAL BLEEDING COMPLICATIONS
In-Hospital Bleeding
Complication
Pharmaco-invasive PPCI P-value
(N=944) (N=948)

Major non-ICH bleeding 6.5% 4.8% 0.11

Minor non-ICH bleeding 21.8% 20.2% 0.40

Blood transfusions 2.9% 2.3% 0.47

 STREAM Trial
30-Day Death/CHF/Shock/MI

Gershlick AH, et al. Heart 2015;101:692-698

 RESULTS
The primary end point occurred in 116 of 939 patents
(12.4%) in the fbrinolysis group and in 135 of 943 patents
(14.3%) in the primary PCI group (RR in the fbrinolysis
group, 0.86; 95% CI, 0.68 to 1.09; P=0.21)

Emergency angiography in 36.3% of patients in the

fbrinolysis group, remainder: underwent angiography at a
median of 17 hours after randomization

intracranial hemorrhages after protocol amendment, 0.5%

vs. 0.3%, P=0.45)
 Key characteristics of newer thrombolytics
compared to alteplase
Characteristic Alteplase Reteplase Tenecteplase
(rt-PA) (rPA) (TNK-tPA)
Immunogenicity No No No
Plasminogen activation Direct Direct Direct
Fibrin specificity ++ + +++
Plasma half-life 4-6 min 18 min 20 min
Dose 15 mg bolus plus 90 min 10+10MU double ±0.5 mg/kg
infusion up to 85 mg bolus 30 min apart single bolus
PAI-1 resistance No ? Yes
Genetic alteration to No Yes Yes
native t-PA (recombinant version)

Based on Ross AM, Clin Cardiol 1999

 Rekomendasi Terapi Fibrinolitk
Rekomendasi Kelas Level
Terapi Fibrinolitk direkomendasikan diberikan dalam 12 jam sejak I A
awitan gejala pada pasien-pasien tanpa kontraindikasi, apabila IKP
primer tdak bisa dilakukan oleh tm yang berpengalaman dalam
waktu 120 menit sejak kontak medis pertama
Pada pasien yang datang segera <2 jam sejak awitan gejala dengan IIa B
infark yang besar dan risiko perdarahan perdarahan rendah,
fibrinolitk perlu dipertmbangkan bila waktu antara KMP dengan
inflasi balon lebih dari 90 menit
Jika strategi reperfusi adalah fibrinolitk, direkomendasikan untuk I A
memulai terapi di rumah sakit sesegera mungkin*setelah diagnosis
*waktu dari diagnosis IMA-EST sampai fibrinolitk < 30 menit
Direkomendasikan golongan fibrin spesifik (misal tenecteplase, I B
alteplase, atau reteplase)
Separuh dosis tenecteplase hendaknya dipertmbangkan pada IIa B
pasien usia ≥75 tahun

PERKI guidelines 2018

 Rekomendasi Terapi Fibrinolitk
Rekomendasi Kelas Level
Aspirin oral harus diberikan I B
Clopidogrel disarankan untuk diberikan bersama dengan aspirin I A

Antkoagulasi disarankan untuk pasien IMA-EST yang mendapatkan I A

terapi fibrinolitk sampai revaskularisasi (bila dilakukan ) atau selama
pasien dirawat di rumah sakit sampai hari ke 8.
Pilihan Antkoagulan:
• Enoxaparin i.v diikut s.c (lebih dipilih dibandingkan UFH).
• UFH diberikan secara bolus intravena sesuai berat badan dan infus I A
I B

Setelah diberikan fibrinolitk, semua pasien perlu dirujuk ke rumah I A

sakit dengan fasilitas IKP
IKP “rescue” diindikasikan segera bila terapi fibrinolitk gagal (<50% I A
perbaikan segmen ST setelah 60 menit)
Pada pasien yang mendapatkan streptokinase, fondaparinux intravena
secara bolus dilnjutkan dengan dosis subkutan 24 jam kemudian IIA B
 Dosis Fibrinolitk dan ko-terapi anttrombotk
(diadaptasi dari Ibanez et al.,2017)

Obat Terapi Awal

Dosis terapi fibrinolitk
Streptokinase 1.5 juta unit i.v selama 30-60 menit
Kontraindikasi spesifik: terapi streptokinase atau anistreptase sebelumnya
Alteplase (tPA) Bolus 15 mg i.v
0.75 mg/kg i.v selama 30 menit (sampai 50 mg)
Kemudian 0.5 mg/kg i.v selama 60 mnit (sampai 35 mg)
Reteplase(rPA) 10 unit+bolus 10 unit i.v diberikan dengan interval 30 menit
Tenecteplase (TNK- Bolus tunggal i.v:
tPA) 30 mg (6000 IU) jika BB < 60 kg
35 mg (7000 IU) jika BB 60- <70 kg
40 mg (8000 IU) jika BB 70- <80 kg
45 mg (9000 IU) jika BB 80-<90 kg
50 mg (10000 IU) jika BB ≥ 90 kg
Direkomendasikan untuk mengurangi sampai separuh dosis pada pasien
usia ≥ 75 tahun
 Take Home Message
Relevance Pharmacoinvasive Strategy in STEMI

• PPCI performed in timely manner a superior mode of

reperfusion
• Performing PPCI in timely manner not always feasible
– Availability of Cath lab
– 24/7 Nurse tech radiographer
– 24/7 interventionist
• Network development is a prerequisite in
optimizing STEMI treatment
• Pharmacoinvasive vs PPCI similar outcome
• pharmaco invasive strategy with fibrin specific
fibrinolitic agent is the reperfusion strategy of
choice for Indonesia region
http://www.inaheart.org/guidelines