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 NIM Program Studi
1. Evisina Hanafiati Frans 011318116303 Ilmu Kesehatan Anak 2. Indah Asmara Gustarini 01131805630
6
THT-KL
3. Ady Irwansyah 01131818630 3
Ilmu Kedokteran Jiwa
4. Imamuddin Arif W 01131806630 2
Anestesiologi dan Reanimasi
5. Lilik Tri Sulistyowati 01131816630 8
Kedokteran Fisik dan Rehabilitasi
6. Diana Murtiati K 01131824630 1
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 / Population Intervention/ Indicator/ Index Comparison Outcome
Pasien sindroma koroner akut paska implantasi stent Pemberian tiga antiplatelet Pemberian dua antiplatet Menurunkan kejadian re-stenosis IV. 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 Pertanyaan Klinis Jurnal yang Diperoleh
P Pasien sindroma koroner akut paska implantasi stent
499 pasien, dilakukan di 10 Cardiac Center di Korea dalam kurun waktu Desember 2007 s.d Desember 2008
I Pemberian tiga antiplatelet 250 subyek mendapat terapi Aspirin, Clopidogrel dan Cilostazol
C Pemberian dua antiplatelet 249 subyek mendapat terapi Aspirin, Clopidogrel dan Plasebo
O Menurunkan kejadian re-stenosis
Penurunan signifikan In-Stent Restenosis (10,8% vs 19,1%) dan In-Segment (12,2% 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.
Desain Penelitian : Eksperimental
Fokus Jurnal : Terapi
Worksheet yang digunakan pada telaah kritis : Terapi Validity
RAMMBO
Telaah Validity
Jawaban sesuai Worksheet Worksheet
Terapi 1. Recruitment Apakah subjek
mewakili ?
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
elevation myocardial infarction; or inability to follow the protocol”.
2. Allocation Apakah penem- patan I & C diacak dan disembunyikan ? sehingga kelompok-kelompok I & C sebanding pada awal percobaan ? 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 allocation number.”
3. Maintenance Apakah kelompok-kelompok
memperoleh kointervensi yang sama ? apakah ada kecukupan tindak lanjut?
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 every visit.”
4. Measurement Blinding Outcome
Apakah subjek dan penilai disamarkan terhadap perlakuan yang diterima dan/atau apakah pengukurannya objektif? Ya, (Methods, pg. 1266 )
“ QCA analysis. Pre-procedure, post-procedure, 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
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 Simpson’s rule”
“All adverse clinical events
were assessed by an independent events committee blinded
to treatment groups.”
Importancy
Telaah Importancy
Jawaban sesuai Worksheet Worksheet
Terapi
Apakah kemaknaan statistik & kemaknaan klinis dari hasil penelitian tergambar dengan baik?
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.
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 group.
Pengukuran apa yang digunakan dan seberapa dampak perlakuannya? (EER.CER,RRR,ARR,NNT?) 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 %
CER 0,8 % RR 3
ARI 1,6 % NNH 62 Mungkinkah dampak terjadi
karena kebetulan? P-value ?
Interval kepercayaan (CI)?
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 Jawaban
1. Apakah PICO Jurnal yang diperoleh sesuai PICO pertanyaan
klinis Ya
2. Apakah pasien anda cukup mirip dengan pasien dalam penelitian ? Ya 3. Apakah Intervensi / Indikator / Indeks dalam penelitian ini dapat
diterapkan untuk manajemen pasien di lingkungan anda ? Ya 4. Apakah outcomes penelitian ini penting bagi pasien anda ? Ya 5. Apakah potensi manfaat lebih besar / Indikator / potensi
merugikan bila intervensi / indikator / indeks ini diaplikasikan pada pasien anda ?
Ya 6. Apakah hasil penelitian ini dapat diintegrasikan dengan nilai-nilai
serta harapan pasien anda ? 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.
