TELAAH KRITIS JURNAL

A RANDOMIZED DOUBLE BLIND MULTICENTER COMPARISON

STUDY OF TRIPLE ANTIPLATELETS THERAPY WITH
DUAL ANTIPLATELETS THERAPY TO REDUCE RE-STENOSIS
AFTER DRUG-ELUTING STENT IMPLANTATION
IN LONG CORONAY LESSIONS

Pembimbing :
J. Eko Wahono, dr., Sp.S., M.Kes
Peserta Pendidikan Dokter Spesialis I :
No

Nama

.
1.

Evisina Hanafiati Frans

2.

Indah Asmara Gustarini

3.

Ady Irwansyah

4.

Imamuddin Arif W

5.

Lilik Tri Sulistyowati

6.

Diana Murtiati K

NIM

Program Studi

011318116303
01131805630

Ilmu Kesehatan Anak

THT-KL

6
01131818630

Ilmu Kedokteran Jiwa

3
01131806630

Anestesiologi dan Reanimasi

2
01131816630

Kedokteran Fisik dan Rehabilitasi

8
01131824630

Ilmu Bedah Plastik

FAKULTAS KEDOKTERAN UNAIR/RSUD Dr. SOETOMO

AGUSTUS 2013

I.

Pendahuluan.
Sindroma Koroner Akut adalah kegawatan kardiovaskuler yang merupakan
penyebab utama kematian. Kematian terbanyak terjadi di luar rumah sakit. Kematian
yang terjadi sebelum pasien tiba di rumah sakit berhubungan dengan aritmia maligna
( VF/VT ) dimana banyak terjadi setelah empat jam pertama setelah awal serangan.
Kematian di rumah sakit lebih banyak berhubungan dengan menurunnya curah
jantung, termasuk gagal jantung kongestif dan syok kardiogenik. Kematian
berhubungan pula dengan luasnya infark miokard. Oleh karena itu upaya untuk
membatasi luas infark akan menurunkan mortalitas.
Data yang dikumpulkan di Amerika menyebutkan bahwa sebanyak 12.200.000
orang mengalami infark miokard, angina pectoris atau keduanya. Sebanyak 5.315.000
orang Amerika datang ke IGD dengan keluhan nyeri dada pada tahun 1997. Sebanyak
225.000 orang meninggal karena serangan jantung sebelum ditangani di rumah sakit.
(WHO 2000, NCHS 2000 AHA - 2000 Heart and Stroke Statistical Update ).
Berbagai macam terapi dikembangkan untuk mengurangi angka kematian
akibat sindroma koroner akut. Dimulai dengan penggunaan kombinasi antara dua obat
antiplatelet dan kombinasi tiga obat antiplatelet, sampai dengan tindakan minimal
invasif. Pemasangan stent merupakan prosedur yang sudah banyak dilakukan untuk
mencegah oklusi arteri koroner. Akhir-akhir ini, Drug Eluting Stent (DES) sering
digunakan untuk terapi perkutan pada penyakit arteri koroner. Pelepasan lokal obat
antiproliferatif pada penggunaan DES secara signifikan mengurangi insiden in-stent
restenosis (ISR). Beberapa percobaan klinis acak menunjukkan bahwa hasil
pemasangan DES mengurangi kejadian ISR dibanding dengan Bare Metal Stent (BMS).

II.

Pertanyaan Klinis.
Pada pasien sindroma koroner akut setelah dilakukan implantasi stent, apakah
pemberian kombinasi tiga obat antiplatelet mengurangi kejadian re-stenosis lebih baik
bila dibanding dengan pemberian kombinasi dua obat antiplatelet ?

III.

Formulasi Pertanyaan Klinis dalam PICO Penelusuran Bukti.

Patient / Problem /

Intervention/

Population

Indicator/

Comparison

Outcome

Index
1

Pasien sindroma

Pemberian tiga

Pemberian dua

Menurunkan

koroner akut paska

antiplatelet

antiplatet

kejadian re-

implantasi stent
IV.

stenosis

Penyusunan Struktur Umum PICO untuk Penelusuran Bukti.

Struktur Umum Penelusuran Bukti:
( Patient post stent implantation OR drug Eluting stent Implantation OR Bare Metal
Stent Implantation ) AND (aspirin, clopidogrel, cilostazol OR Triple antiplatelets drug)
AND (aspirin, clopidogrel OR Dual antiplatelets drug ) AND ( Re-stenosis )

V.

Bukti (Jurnal) Terbaik yang Diperoleh

Penulis:
Seung Whan Lee , et all
Judul:
A Randomized Double Blind Multicenter Comparison Study of Triple Antiplatelets
Therapy with Dual Antiplatelets Therapy to Reduce Re-stenosis after Drug-Eluting
Stent Implantation in Long Coronary Lessions
Nama & Tahun Jurnal:
Journal of The American College Cardiology volume 57 no. 11, 2011

VI.

Relevansi PICO Pertanyaan Klinis dengan PICO Jurnal

PIC
O
P

Pertanyaan Klinis
Pasien sindroma koroner
akut paska implantasi stent

Pemberian tiga antiplatelet

Pemberian dua antiplatelet

Jurnal yang Diperoleh

499 pasien, dilakukan di 10 Cardiac Center
di Korea dalam kurun waktu Desember
2007 s.d Desember 2008
250 subyek mendapat terapi Aspirin,
Clopidogrel dan Cilostazol
249 subyek mendapat terapi Aspirin,
Clopidogrel dan Plasebo
Penurunan signifikan In-Stent Restenosis
(10,8% vs 19,1%) dan In-Segment (12,2%

Menurunkan kejadian restenosis

vs 20% ) setelah follow up 8 bulan pada

kelompok yang mendapat tripel terapi
dibanding kelompok yang mendapat dual
terapi.

VII.

Desain Penelitian, Fokus dan Worksheet yang digunakan untuk telaah kritis dari
Jurnal yang diperoleh.
2

Desain Penelitian
: Eksperimental
Fokus Jurnal
: Terapi
Worksheet yang digunakan pada telaah kritis : Terapi
Validity
RAMMBO
1. Recruitment

Telaah Validity
Worksheet
Terapi
Apakah subjek
mewakili ?

Jawaban sesuai Worksheet

Ya,
(Methods, pg. 1265 )
This prospective, doubleblind, randomized
study (DECLARE-LONG II [Drug-Eluting
Stenting Followed by Cilostazol Treatment
Reduces Late Restenosis in Patients with
Long Coronary Lesions] trial) involved 499
patients 18 years of age or older with stable
angina or acute coronary syndrome and a
native long coronary lesion (length 25
mm, a diameter stenosis 50%, and visual
reference diameter 2.5mm). The study
involved 10 cardiac centers in Korea
between December 2007 and December
2008. Patients were excluded if they had
contraindication to aspirin, clopidogrel, or
cilostazol; left main disease; graft vessel
disease; left ventricular ejection fraction
<30%; recent history of hematologic
disease or leukocyte count <3,000/mm3,
platelet count < 100,000/ mm3, or both;
hepatic dysfunction with aspartate
aminotransferase or alanine
aminotransferase 3 times or more of the
upper normal limit; history of renal
dysfunction or serum creatinine level 2.0
mg/dl; serious noncardiac disease with a life
expectancy <1 year; planned bifurcation
stenting in side branch; ST-segment
3

elevation myocardial infarction; or inability

2. Allocation

Apakah penempatan I & C diacak

dan disembunyikan
?
sehingga
kelompokkelompok I & C
sebanding pada
awal percobaan ?

to follow the protocol.

Ya,
( Methods, pg. 1265 )
Randomization and procedures. After
successful ZES implantation (stent length
30 mm), patients were allocated randomly
in a 1:1 ratio to triple antiplatelet group
(aspirin, clopidogrel, and cilostazol, triple
group: n =250) or dual antiplatelet therapy
(aspirin, clopidogrel, and placebo, dual
group: n =249) using an interactive web
response system. Stratified and block
randomization was performed according to
participation sites. A matching box of 100
mg cilostazol and placebo (tablet identical
to cilostazol) were prepared with a patient

3. Maintenance

Apakah kelompokkelompok
memperoleh
kointervensi yang
sama ? apakah ada
kecukupan tindak
lanjut?

allocation number.
Ya,
( Methods, pg. 1265-1266 )
A matching box of 100 mg cilostazol and
placebo (tablet identical to cilostazol) were
prepared with a patient allocation number.
From at least 24 h before the procedure and
thereafter, all patients received aspirin
(loading dose of 200 mg, followed by 200
mg daily indefinitely) and clopidogrel
(loading dose of 300 mg, followed by 75 mg
daily for at least 12 months). Patients also
received a loading dose of 2 study tablets
(cilostazol 200 mg or matching placebo, 2
tablets) within 1 h after the procedure,
followed by cilostazol 100 mg twice daily or
placebo 1 tablet twice daily for 8 months..
Follow-up. Repeat coronary angiography

was performed at 8 months after stenting.

Clinical follow-up visits were scheduled at
30, 120, and 240 days and at 1 year. At
every visit, physical examination,
electrocardiogram, drug compliance,
cardiac events, and angina recurrence were
monitored. Drug compliance was assessed
using a compliance questionnaire.
Laboratory and clinical assessment of
adverse drug side effects were performed at
4. Measurement
Blinding
Outcome

Apakah subjek dan

penilai disamarkan
terhadap perlakuan
yang diterima
dan/atau apakah
pengukurannya
objektif?

every visit.
Ya,
(Methods, pg. 1266 )
QCA analysis. Pre-procedure, postprocedure, and follow-up angiograms
obtained after intracoronary nitroglycerin
administration were submitted to a core
analysis center (Asan Medical Center, Seoul,
Korea). Digital angiograms were analyzed
using an automated edge detection system
(CASS II, Pie Medical, Maastricht, the
Netherlands). QCA measurements were
obtained for both in-stent and in-segment
(stented segment and margins 5 mm
proximal and distal to stent). Patterns of
restenosis were assessed using the Mehran
classification
IVUS imaging and analysis. IVUS
imaging was performed after intracoronary
administration of 0.2 mg nitroglycerin using
motorized transducer pullback (0.5 mm/s)
and a commercial scanner consisting of a
30-MHz transducer within 3.2-F imaging
sheath (SCIMED, Boston Scientific Scimed
Inc., Freemont, California). Quantitative
5

volumetric IVUS analysis was performed by

a core laboratory (Asan Medical Center,
Seoul, Korea). Using computerized
planimetry, stent, lumen, and intimal
hyperplasia (stent minus lumen) areas were
measured every 1 mm within the stented
segment; volumes were calculated using
Simpsons rule
All adverse clinical events
were assessed by an independent events
committee blinded
to treatment groups.

Importancy
Telaah Importancy
Worksheet
Terapi
Apakah kemaknaan statistik &
kemaknaan klinis dari hasil
penelitian tergambar dengan
baik?

Jawaban sesuai Worksheet

Ya,
( Result, pg. 1267-1268 )
The in-stent (0.56 0.55 mm vs. 0.68 0.59 mm,
p = 0.045, absolute reduction: 0.12, 95% CI: 0.02
to 0.22) and in-segment (0.32 0.54 mm vs. 0.47
0.54 mm, p = 0.006, absolute reduction: 0.15,
95% CI: 0.04 to 0.42) late loss were significantly
lower in the triple group than in the dual group.
In-stent and in-segment minimum lumen diameter
was larger in the triple group than in the dual
group. Consequently, in-stent restenosis (10.8%
vs. 19.1%, relative risk: 0.57, 95% CI: 0.35 to
0.91, p = 0.016) and in-segment restenosis
(12.2% vs. 20.0%, relative risk:
0.61, 95% CI: 0.39 to 0.96, p = 0.028) was
significantly lower in the triple group than in the
dual group.
6

ischemic-driven TLR (5.2% vs. 10.0%, relative

risk: 0.52, 95% CI: 0.27 to 0.99, p = 0.042) and
ischemic-driven TVR (5.2% vs. 10.4%, relative
risk: 0.50, 95% CI: 0.26 to 0.95, p = 0.029) were
significantly lower in the triple versus the dual
Pengukuran apa yang
digunakan dan seberapa
dampak perlakuannya?
(EER.CER,RRR,ARR,NNT?)

group.
Instent restenosis :
EER10,8%
CER19,1%
RR 0.57
ARR 8,3 %
RRR 41 %
NNT 12
( RR 0,57 ; 95 % CI: 0,35-0,91; p=0,016 )
Insegment restenosis :
EER12,2%
CER20,0%
RR 0.61
ARR 7,8 %
RRR 39 %
NNT 12
( RR 0,61; 95 % CI : 0,39-0,96; p=0,028 )
Ischemic Driven TLR :
EER 5,2 %
CER 10 %
RR 0,52
ARR 4,8 %
RRR 48 %
NNT 20
( RR 0,52; 95 % CI : 0,27-0,99; p=0,042 )
Ischemic Driven TVR :
EER 5,2 %
CER 10,4 %
RR 0,5
ARR 5,2 %
RRR 50 %
NNT 19
( RR 0,5; 95 % CI : 0,26-0,95; p=0,029 )
Headache :
EER 4,4 %
CER 0,8 %
RR 5,5
ARI 3,6 %
NNH 27
Gastrointestinal trouble :
EER 2,4 %

Mungkinkah dampak terjadi

karena kebetulan?
P-value ?
Interval kepercayaan (CI)?

CER 0,8 %
RR 3
ARI 1,6 %
NNH 62
Tidak,
in-stent restenosis (10.8% vs. 19.1%, relative
risk: 0.57, 95% CI: 0.35 to 0.91, p = 0.016)
in-segment restenosis (12.2% vs. 20.0%, relative
risk: 0.61, 95% CI: 0.39 to 0.96, p = 0.028)
ischemic-driven TLR (5.2% vs. 10.0%, relative
risk: 0.52, 95% CI: 0.27 to 0.99, p = 0.042 )
ischemic-driven TVR (5.2% vs. 10.4%, relative
risk: 0.50, 95% CI: 0.26 to 0.95, p = 0.029) were
significantly lower in the triple versus the dual
group.

Applicability
No

Telaah Applicability

.
1.

Apakah PICO Jurnal yang diperoleh sesuai PICO pertanyaan

2.
3.

klinis
Apakah pasien anda cukup mirip dengan pasien dalam penelitian ?
Apakah Intervensi / Indikator / Indeks dalam penelitian ini dapat

4.
5.

diterapkan untuk manajemen pasien di lingkungan anda ?

Apakah outcomes penelitian ini penting bagi pasien anda ?
Apakah potensi manfaat lebih besar / Indikator / potensi
merugikan bila intervensi / indikator / indeks ini diaplikasikan

6.

pada pasien anda ?

Apakah hasil penelitian ini dapat diintegrasikan dengan nilai-nilai
serta harapan pasien anda ?

Jawaban
Ya
Ya
Ya
Ya
Ya

Ya

VIII. Kesimpulan
1. Penelitian yang dilaporkan dalam jurnal tersebut Valid
2. IMPORTANCY dalam penelitian tersebut tergambar dalam jurnal.
3. Hasil penelitian yang dilaporkan dalam jurnal tersebut bersifat Aplicable untuk
pasien.