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
1
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
I
Pemberian tiga antiplatelet
C
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%
O
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
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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 Simpson’s 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 %
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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.
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