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Abstrak :
Latar Belakang. Clopidogrel adalah salah satu pilihan antiplatelet pada kasus stroke iskemik yang bekerja dengan menghambat ikatan adenosine diphosphate (ADP) dengan reseptor P2Y12. Gen ABCB1 diketahui mengkode transporter P-glikoprotein (P-gp) multidrug resistance-1 (MDR1) yang mempengaruhi absorpsi clopidogrel di usus, sehingga mempengaruhi efektivitasnya dalam mencegah agregasi trombosit. Penelitian ini bertujuan untuk menilai peran polimorfisme gen ABCB1 terhadap variabilitas respons clopidogrel yang dilihat dari agregasi trombosit serta mengetahui frekuensi genotip ABCB1 pada populasi. Metode. Studi potong lintang dilakukan pada pasien stroke iskemik yang mengkonsumsi clopidogrel di RSUI/RSCM pada 2020-2023. Dilakukan pemeriksaan polimorfisme ABCB1 C3435T dan C1236T serta agregasi trombosit dengan VerifyNow PRU. Variabilitas respons clopidogrel dikelompokkan menjadi tidak respons (>208 PRU), respons (95-208 PRU), dan risiko perdarahan (<95 PRU). Hasil. Sebanyak 124 subjek direkrut dalam penelitian, dengan 12,9% subjek tidak respons, 45,9% respons, dan 41,9% lainnya memiliki risiko perdarahan terhadap pemberian clopidogrel. Genotip homozigot wildtype (CC) pada ABCB1 C1236T memiliki kemungkinan risiko perdarahan pada konsumsi clopidogrel 3,76 kali lebih tinggi (p=0,008; 95%CI 1,41-10,07) dibandingkan varian lainnya (CT/TT). Frekuensi genotip ABCB1 C3435T subjek pada kelompok homozigot wildtype, heterozigot, dan homozigot varian berturut-turut sebesar 35,9%, 43,5% dan 16,9%. Sementara itu, pada genotip C1236T berturut-turut sebesar 17,8%, 39,5%, dan 42,7%. Kesimpulan. Genotip ABCB1 C1236T varian homozigot wildtype memiliki kemungkinan risiko perdarahan 3,76 kali lebih tinggi pada pemberian clopidogrel. Frekuensi genotip terbanyak pada ABCB1 C1236T adalah homozigot varian, sementara pada ABCB1 C3435T adalah heterozigot. ......Background. Clopidogrel has been the primary choice of antiplatelet in ischemic stroke that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. P-glycoprotein (P-gp) multidrug resistance-1 (MDR1) is a transmembrane efflux transporter in intestinal cells that plays a significant role in clopidogrel absorption, therefore may affect platelet aggregation. P-gp is encoded by the ABCB1 gene. This study aims to evaluate the effect of ABCB1 polymorphism on clopidogrel response variability in ischemic stroke patients and its genotype frequency. Methods. A cross-sectional study was conducted in ischemic stroke patients who received clopidogrel between 2020-2023 in RSUI/RSCM. All subjects were assessed for ABCB1 polymorphisms C3435T and C1236T. Platelet aggregation were measured using VerifyNow PRU. Clopidogrel response variability was classified into unresponsive (>208 PRU), responsive (95-208 PRU), and bleeding risk (<95 PRU). Results. 124 subjects enrolled in this study, with 12,9% of subjects classified as non-responsive/resistant, 49,5% as responsive, and 41,9% as bleeding risk. ABCB1 C1236T homozygote wildtype (CC) was associated with 3,76 times higher bleeding risk than other variants (p=0,008; 95%CI 1,41-10,07). Genotype frequency of ABCB1 C3435T homozygote wildtype, heterozygote, and homozygote variants were 35,9%, 43,5% and 16,9%, respectively; while the genotype frequency of ABCB1 C1236T were 17,8%, 39,5%, and 42,7%, respectively. Conclusion. ABCB1 C1236T homozygote wildtype was associated with 3,76 times higher bleeding risk than other variants. The most common genotype frequency of ABCB1 C1236T was homozygote variant; while for ABCB1 C3435T was heterozygote.

Abstrak :
ABSTRAK
Praktik Kerja Profesi Apoteker PKPA di Apotek Rini bertujuan untuk memahami tugas dan tangung jawab apoteker di apotek dan memiliki pengalaman praktik pelayanan kefarmasi di apotek. Tugas khusus yang diberikan yaitu Pengkajian Interaksi Obat pada Resep yang Mengandung Clopidogrel di Apotek Rini Bulan Januari Tahun 2017. Tujuannya yaitu untuk mengetahui jumlah total dan persentase resep yang mengandung interaksi clopidogrel dengan obat lain pada tahun 2017 dan mengetahui manjemen klinis yang perlu dilakukan. Berdasarkan data yang diperoleh total resep yang mengandung interaksi adalah 61 lembar dengan persentase sebesar 0,363 .

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ABSTRACT
Pharmacist Profession Internship Program PKPA at Apotek Rini aims to understand the duties and responsibilities of pharmacists in pharmacies and to have pharmaceutical care practice experience in pharmacies. The specific task given is the Drug Interaction Assessmen on Clopidogrel Prescription at Rini Pharmacy January of 2017. The purpose of this particular task is to determine the total number and percentage of prescriptions containing clopidogrel interactions with other drugs and to determine which clinical management needs to be done. Based on data obtained, total recipe containing interaction is 61 sheets with percentage of 0.363 .

Abstrak :
Tujuan : Mendapatkan perbandingan reaktifitas platelet jam pertama (dengan alat Multiplate) antara ticagrelor dan clopidogrel. Latar Belakang : Ticagrelor memiliki kemampuan inhibisi platelet lebih baik dibandingkan clopidogrel. Penelitian PLATO atau substudi PLATO-platelet, dosis clopidogrel hanya 300 mg, dibandingkan dengan ticagrelor 180 mg pada pasien STEMI. Penelitian ini dilakukan untuk menilai reaktifitas platelet pada jam-1,4 dan 8 antara ticagrelor 180 mg atau clopidogrel 600 mg pada pasien STEMI. Metode : Penelitian random clinical trial, double blind, pasien STEMI dengan naive clopidogrel atau ticagrelor, dilanjutkan tindakan intervensi perkutan primer (PPCI) di RS Jantung Harapan Kita dari April-Juni 2013. Aktifitas platelet diukur jam pertama, jam keempat dan kedelapan dengan alat Multiplate. Hasil : Didapat 22 pasien STEMI nave clopidogrel/ticagrelor, dengan 11 pasien tiap kelompok. Tidak terdapat perbedaan terhadap usia, onset iskemik, BMI, penyakit penyerta Diabetes Melitus serta waktu pengambilan sampel pemeriksaan antara 2 kelompok obat. Didapat nilai reaktifitas platelet tetap tinggi pada kelompok obat clopidogrel dibandingkan ticagrelor pada jam pertama. Hasil kelompok ticagrelor tetap konstan hingga jam ke-8. Dan penurunan rekatifitas platelet kelompok clopidogrel menurun mendekati nilai yang diharapkan hingga jam 8. Kesimpulan : Reaktifitas platelet ticagrelor lebih rendah dibandingkan clopidogrel saat jam pertama pasca loading obat. Terdapat 45% (5 pasien) pada kelompok clopidogrel yang tetap memiliki reaktifitas platelet tinggi pada pemeriksaan jam pertama, keempat dan kedelapan, serta 9% (1 pasien) pada ticagrelor yang memiliki kenaikan nilai reaktifitas platelet pada jam keempat dan kedelapan ......Objectives : This study sought to compare platelet reactivity by180 mg ticagrelor and 600 mg clopidogrel in primary PCI STEMI patients. Background: The ability of ticagrelor in inhibiting platelet functions was more potent than clopidogrel in stable CAD and UAP/NonSTEMI patients. According to the PLATO trial or PLATO-platelet substudy, patients treated with 180 mg ticagrelor had better clinical endpoint and more platelet inhibition compared to 300 mg clopidogrel. The study we conducted was to see the platelet reactivity at 1st, 4th, and 8th hour after ingestion of 180 mg ticagrelor compared to 300 mg clopidogrel in STEMI patients Methods: This is a randomized double blind clinical trial carried out in Department of Cardiology and Vascular Medicine Universitas Indonesia/ National Cardiovascular Center Harapan Kita in April - June 2013. As many as 22 clopidogrel or ticagrelor nave STEMI patients undergoing primary PCI with were recruited. Platelet reactivity (PRU) was assessed by Multiplate at 1,4,8 h after LD. Result : Both nave ticagrelor and clopidogrel goups had 11 patients each. About 45% patients in clopidogrel group have high reactivity platelet at 1h, 4h and 8 h MEA analysis, and 9% patients in ticagrelor group have high reactivity platelet at 4h and 8 h MEA analysis. Conclusion: The action of Ticagrelor in platelet reactivity was lower compared to Clopidogrel in STEMI patients. 45 % patients in clopidogrel group maintained high platelet reactivity at 1st, 4th and 8th hour after LD, while 9% patients in ticagrelor group had high platelet reactivity started at 4th up 8th hour after LD.

Abstrak :
Dual antiplatelet therapy (DAPT) is the mainstay of secondary prevention treatment for acute coronary syndrome (ACS) and ischemic stroke, especially after coronary intervention. DAPT consists of aspirin and P2Y12 receptor inhibitor (e.g. clopidogrel), and the use of DAPT has been increased over time. The most serious and common adverse effect is gastrointestinal bleeding. Guidelines in managing such condition are available among Gastroenterologist Societies and Cardiologist Societies. Most guidelines are consistent with each other to continue the use of aspirin while withholding P2Y12. However, European Society of Cardiologist (ESC) guideline in 2017 recommends P2Y12 receptor inhibitor as the preferred antiplatelet for patient with upper gastrointestinal bleeding. This review will look on the guidelines and other supporting evidence for the justification on the antiplatelet of choice.

Abstrak :
Latar Belakang: Respon antar-individu yang bervariasi terhadap obat antiplatelet (clopidogrel) telah dilaporkan. Perbedaan tingkat metabolisme clopidogrel untuk metabolit aktif tiol menggambarkan variabilitas antar-individu dalam penghambatan trombosit. Sitokrom P4502C19 (CYP2C19) memetabolisme zat metabolit aktif tiol. Carier polimorfisme yang menyebabkan hilangnya fungsi CYP2C19 * 2 dan * 3 alel pada terapi antiplatelet mengakibatkan berkurangnya penghambatan agregasi trombosit. Informasi mengenai hubungan antara CYP2C19 * 2 dan * 3 dengan inhibisi agregasi trombosit pada pasien Sindroma koroner akut di Indonesia masih terbatas. Tujuan dari penelitian ini adalah untuk mengetahui hubungan antara dua varian, CYP2C19 * 2 (6816>A) dan CYP2C19 * 3 (636G>A) terhadap penurunan fungsi inhibisi agregasi trombosit. Bahan dan Metode: Desain penelitian cross sectional. Jumlah responden adalah 114 orang (dipilih berdasarkan kriteria inklusi dan kriteria ekslusi). Pemeriksaan polimorfisme CYP2C19 dilakukan dengan menggunakan teknik Real Time-Polymerase Chain Reaction (RT-PCR) TaqMan SNP Genotyping Assays dengan alat dari applied Biosystems 7500 Fast/7900HT Fast Real Time PCR Systems (in standart or 9600 emulation mode). Inhibisi agregasi trombosit diperiksa dengan menggunakan metode Light Transmisi Aggregometry (LTA) dengan alat Helena AggGRAM Analyzer pada penambahan 5umol/L ADP sebagai agregator. Hasil: Distribusi inhibisi agregasi trombosit menunjukkan perbedaan rerata antara responden non carier polimorfisme dengan responden carier polimorfisme (16,9 CI95%: 12,1-21,6 vs 9,4 CI95%: 2,9 - 15,0). Analisis regresi linier menunjukkan bahwa responden carier polimorfisme memiliki inhibisi agregasi trombosit lebih rendah dibandingkan dengan responden non carier polimorfisme. Analisis regresi logistik menunjukkan bahwa responden carier polimorfisme mempunyai odds untuk merespon kurang baik terhadap clopidogrel sebesar 1,9 kali jika dibandingkan dengan responden yang non carier setelah dikontrol oleh variabel umur dan jenis kelamin, hal tersebut mengindikasikan bahwa carier polimorfisme mempunyai inhibisi yang rendah terhadap agregasi trombosit. Kesimpulan: Temuan kami membuktikan adanya hubungan antara CYP2C19 * 2 dan * 3 polimorfisme dengan inhibisi agregasi trombosit. ...... Background: Inter-individual variability in response to antiplatelet drugs (clopidogrel) has been reported. The difference in the extent of metabolism of clopidogrel to its active metabolite tiol is the most plausible mechanism for the observed inter-individual variability in platelet inhibition. The cytochrome P4502C19 (CYP2C19) metabolizes the active metabolite tiol. The carrier polymorphisms of reduced - functions of CYP2C19*2 and *3 allele on antiplatelet therapy showed diminished platelet aggregation inhibition. There is limited information on the association between CYP2C19 *2 and *3 with platelet aggregation inhibition in ACS patients generally in Indonesia Population. The aim of this study was to determine the association between two variants, CYP2C19*2 (6816>A) and CYP2C19*3 (636G>A) reduced function with platelet aggregation inhibition. Material & Method: a cross sectional study was done with 114 subjects (selected by inclusions and exclusions criteria). The CYP2C19 polymorphisms were genotype using the PCR method with TaqMan SNP Genotyping Assays from applied Bio systems 7500 Fast/7900HT Fast Real Time PCR Systems (in standard or 9600 emulation mode). The platelet aggregation inhibition was tested using Light Transmission Aggregometry (LTA) by Helena AggGRAM Analyzer with 5umol/L ADP as aggregator. Results: The distribution of platelet inhibition aggregation showed difference between respondents with non-carrier polymorphisms and carrier polymorphisms (16,9 CI95%: 12,1 -21,6 vs 9,4 CI95%: 2,9 - 15,0). The linier regression analysist indicated that the carrier polymorphisms have lowest platelet aggregation inhibition compared with non-carrier polymorphisms. The logistic regression analysis indicated that carrier polymorphisms respondents has 1,9 odds to be low response to clopidogrel if compared with non-carrier polymorphisms respondents after adjusted with age and sex and it is indicated that it has low platelet aggregation inhibition. Conclusion: Our present findings the evidence of an association between CYP2C19 *2 and *3 polymorphisms and platelet aggregation inhibition.

Abstrak :
ABSTRAK
Klopidogrel merupakan salah satu terapi standar pada pasien SKA dan/atau pasien post IKP. Penggunaan klopidogrel di Indonesia sangat tinggi, namun diduga berbagai faktor dapat menyebabkan variasi hambatan agregasi trombosit yang mengakibatkan resistensi klopidogrel. Sebanyak 100 pasien SKA dan/atau post IKP diperiksa agregasi trombosit dengan metode LTA menggunakan ADP 20 M dan diambil data demografi, klinis, terapi, serta data polimorfisme genetik CYP2C19 2 dan 3. Resisten klopidogrel ditetapkan sebagai persen agregasi trombosit >59 . Proporsi resistensi klopidogrel sebanyak 36 36 . Faktor yang berperan terhadap resistensi klopidogrel adalah tidak merokok, DM, CYP2C19 2 dan 3 dengan prediktor paling dominan adalah polimorfisme CYP2C19 2.Kata kunci : klopidogrel, resistensi, agregasi, trombosit, CYP2C19

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ABSTRACT
Clopidogrel has become the standard therapy in patients with ACS and or post PCI. The use of clopidogrel in Indonesia is very high, but expected many factors can cause variability inhibition of platelet aggregation resulting clopidogrel resistance. Total of 100 patients with ACS and or post PCI were measured with platelet aggregation by LTA method using 20 M ADP and retrieved data of demographic, clinical, therapeutic, and the data on genetic polymorphism CYP2C19 2 and 3. Clopidogrel resistance was defined as percent platelet aggregation 59 . The proportion of clopidogrel resistant were 36 36 . Factors that contribute to clopidogrel resistance are non smoking status, diabetes, CYP2C19 2 and 3 with the most dominant predictor is polymorphism CYP2C19 2.Keywords clopidogrel, resistance, aggregation, platelet, CYP2C19

Abstrak :
ABSTRAK
Kemungkinan terjadinya stroke berulang setelah stroke pertama adalah lebih dari 3 sampai 10 pada bulan pertama dan 5 sampai 14 dalam tahun pertama. Klopidogrel terbukti menjadi obat yang aman dan efektif untuk pencegahan sekunder kejadian vaskular. Tujuan dari penelitian ini adalah untuk mengetahui pengaruh klopiogrel dalam pencegahan stroke berulang. Studi ini menggunakan rancangan kasus kontrol. Data diambil dari rekam medis pasien di instalasi rekam medis RSUD Dr. Moewardi Surakarta periode Januari 2013-Februari 2017. Kelompok kasus adalah pasien stroke berulang yang menerima asetosal atau klopidogrel. Kelompok kontrol adalah pasien stroke tidak berulang yang menerima asetosal atau klopidogrel. Sebanyak 105 rekam medis memenuhi kriteria inklusi. Pasien yang menggunakan klopiogrel mempunyai risiko pencegahan terhadap stroke berulang. Namun secara statistik tidak signifikan berbeda. Analisis bivariate menunjukkan bahwa jenis kelamin, riwayat DM dan riwayat hipertensi mempunyai pengaruh terhadap kejadian stroke berulang. Dari analisis multivariate didapatkan hasil bahwa laki-laki mempunyai risiko 2,328 kali untuk stroke berulang p=0,047 , riwayat DM mempunyai risiko 3,975 kali untuk stroke berulang p=0,016 , riwayat hipertensi mempunyai risiko 4,021 kali untuk stroke berulang p=0,03 . Klopidogrel tidak mempunyai pengaruh terhadap stroke berulang, laki-laki, riwayat hipertensi, diabetes melitus mempunyai pengaruh terhadap kejadian stroke berulang.

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ABSTRACT
The likelihood of recurrent stroke after the first stroke is more than 3 to 10 in the first month and 5 to 14 within the first year. Clopidogrel proves to be a safe and effective drug for the prevention of secondary vascular events. The purpose of this study was to determine the effect of clopidogrel in the prevention of recurrent stroke. This study used case control design. Data taken from patient 39 s medical record at medical record installation of RSUD Dr. Moewardi Surakarta period January 2013 February 2017. Case group is a recurrent stroke patient receiving an acetosal or clopidogrel. The control group is a non recurrent stroke patient who receives an acetosal or clopidogrel. A total of 105 medical records meet the inclusion criteria. Patients who use clopidogrel have a risk of prevention of recurrent stroke. But statistically not significantly different. Bivariate analysis showed that gender, history of DM and history of hypertension had an effect on recurrent stroke events. From the multivariate analysis, it was found that men had a risk of 2.328 for recurrent stroke p 0.047 , the history of DM had a risk of 3.975 times for recurrent stroke p 0.016 , history of hypertension was 4.021 times for recurrent stroke p 0.03 . Clopidogrel has no effect on recurrent stroke, male history of hypertension, history of hypertension has an effect on recurrent stroke events.

Abstrak :
ABSTRAK
Klopidogrel merupakan obat antiplatelet yang konsentrasinya sangat kecil dalam plasma. Klopidogrel merupakan obat wajib uji bioekivalensi karena merupakan critical use drug yaitu obat yang digunakan pada kondisi serius. Penelitian ini bertujuan untuk melakukan perhitungan kadar klopidogrel dalam plasma subjek sehat sehingga didapatkan profil farmakokinetika klopidogrel. Pada penelitian ini dilakukan analisis klopidogrel secara in vivo dalam plasma tiga subjek sehat secara kromatografi cair kinerja ultra tinggi tandem spektrometri massa KCKUT-SM/SM menggunakan metode yang telah tervalidasi. Sampel plasma diambil setelah subjek diberikan tablet klopidogrel dengan dosis 75 mg sebanyak 14 titik yaitu pada jam ke 0 predose ; 0,25; 0,5; 0,75; 1; 1,25; 1,5; 2; 3; 4; 8; 12; 18; dan 24. Validasi parsial yang dilakukan berupa akurasi dan presisi serta linearitas kurva kalibrasi. Akurasi dan presisi menghasilkan diff dan koefisien variasi KV tidak lebih dari 15 dan tidak lebih dari 20 pada konsentrasi LLOQ. Kurva kalibrasi yang linear didapat pada rentang 20 ndash; 5000 pg/mL. Metode ini telah memenuhi syarat validasi sesuai EMEA Guidelines. Profil farmakokinetika klopidogrel diperoleh berturut-turut sebagai berikut; konsentrasi maksimum Cmax = 1,146 ng/mL; waktu pada konsentrasi maksium tmax = 1 jam; waktu paruh t = 7,01 jam; AUC0-t = 7,420 ng jam/mL; dan AUC0- = 8,111 ng jam/mL.

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ABSTRACT
Clopidogrel is an antiplatelet drug with a very low plasma concentration. Clopidogrel is a drug that requires bioequivalence test because it is a critical use drug that is used in serious condition. The aim of this study is to perform calculation of clopidogrel concentration in the plasma of healthy subjects to obtain a pharmacokinetics profile of clopidogrel. In this study, clopidogrel analysis was performed in vivo in plasma of three healthy subjects by ultra high performance liquid chromatography ndash tandem mass spectrometry UPLC MS MS using validated methods. Plasma samples were taken after subjects were given clopidogrel tablets with doses of 75 mg at 14 points at 0 predose 0,25 0,5 0,75 1 1,25 1,5 2 3 4 8 12 18 dan 24. Partial validation parameters were intra day accuracy and precicsion and linearity of the calibration curve. Intra day accuracy and precicsion produced diff and coefficient of variation CV not more than 15 and not more than 20 at LLOQ concentration. A linear calibration curve produced in the range of 20 ndash 5.000 pg mL. This method has been fulfilled the criteria for validation accordance to EMEA Guidelines. Pharmacokinetic profile of clopidogrel was obtained respectively as follows maxium concentration Cmax 1.146 ng mL time at maximum concentration tmax 1 hour half life t 7.01 hour AUC0 t 7.420 ng h mL dan AUC0 8.111 ng h mL.

Abstrak :
Studi mengenai pemberian klopidogrel sebelum angiografi koroner (pretreatment) pada pasien infark miokard akut dengan elevasi segmen ST (IMA-EST) yang akan menjalani intervensi koroner perkutan primer (IKPP) terbatas, namun dapat disimpulkan bahwa aman dan dapat penurunan angka major adverse cardiovascular events (MACE). Pada studi yang dilakukan beberapa tahun terakhir, manfaat pemberian klopidogrel pretreatment dipertanyakan. Studi yang telah ada dilakukan di negara lain berbeda dengan kondisi di Indonesia; terdapat perbedaan karakteristik seperti waktu onset nyeri dada hingga pasien sampai ke fasilitas kesehatan primer, loading antiplatelet, serta dilakukan tindakan IKPP yang lebih panjang. Penelitian ini bertujuan untuk mengetahui hubungan pemberian klopidogrel pretreatment  dengan TIMI-flow pasien IMA EST yang menjalani IKPP. Studi potong lintang retrospektif terhadap 220 pasien IMA EST dilakukan di rumah sakit Jantung dan Pembuluh Darah Harapan Kita sejak tanggal 1 Januari - 30 Oktober 2018 dengan membagi subjek dalam kelompok klopidogrel pretreatment (600 mg klopidogrel diberikan > 120 menit sebelum angiografi koroner) dan kelompok yang diberikan < 120 menit. Analisis multivariat menunjukkan bahwa klopidogrel pretreatment merupakan prediktor utama yang mempengaruhi TIMI flow sebelum tindakan IKPP (OR 0.273, 95% CI 0.104-0.716; p=0.008). Pemberian klopidogrel pretreatment berhubungan dengan TIMI flow sebelum tindakan IKPP, namun tidak berpengaruh terhadap TIMI setelah dilakukan tindakan IKPP.  ......Immediate antiplatelet administration is the standard therapy used in acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Studi on clopidogrel pretreatment are limited, but it can be concluded that was safe, also reduced the number of major adverse cardiovascular events (MACE). Recently, pretreatment with P2Y12 are questioned. There are differences in the background and the conditions between the studies that have been conducted and the condition in Indonesia; such as duration of angina onset until arrive at primary health care, time of loading antiplatelet and longer ischemic time. This study sought to evaluate the association between clopidogrel pretreatment and TIMI flow of patients with acute STEMI undergoing primary PCI. Single-center retrospective cross sectional study of 220 patients with acute STEMI were conducted in National Centre of Cardiovascular Harapan Kita, Indonesia from 1 January-30 October 2018. Subjects are devided into two groups: clopidogrel pretreatment (≥ 120 minute from coronary angiography conducted) and non pretreatment group (<120 minute). Multivariate analysis revealed that clopidogrel pretreatment is the main predictor of preprocedural TIMI grade flow (OR 0.273, 95% CI 0.104-0.716; p=0.008). Clopidogrel pretreatement was associated with TIMI flow grade pre intervention, but not with TIMI flow grade post intervention.

Abstrak :
Latar belakang: Resistensi klopidogrel merupakan salah satu faktor risiko penting terjadinya kejadian iskemik berulang pada pasien yang telah mendapat terapi anti platelet yang optimal. Penelitian ini bertujuan untuk mengetahui peran metilasi DNA gen CYP2C19 sebagai salah satu faktor epigenetik terhadap kejadian resistensi klopidogrel pada pasien infark miokard akut dengan elevasi segmen ST (IMA-EST) yang menjalani intervensi koroner perkutan primer (IKPP). Metode: Pasien IMA-EST yang menjalani IKPP diberikan antiplatelet klopidogrel dan menjalani pemeriksaan fungsi platelet degan VerifyNowTM. Kriteria untuk mendefinisikan resistensi klopidogrel adalah nilai PRU >208. Pemeriksaan metilasi DNA gen CYP2C19 dilakukan dengan metode bisulfite genomic sequencing technology. Data klinis, laboratorium, dan angiografik termasuk TIMI flow dikumpulkan untuk dilakukan analisis. Hasil: Dari 122 subjek, resistensi klopidogrel ditemukan pada 22% subjek. Kelompok dengan presentase metilasi DNA <50% mempunyai risiko lebih tinggi terjadinya resistensi klopidogrel (OR 4.5 IK95% 2.1-9.3, nilai p 0.018). Grup ini juga diketahui mempunyai TIMI flow post-IKPP yang suboptimal (OR 3.4 IK95% 1.3 - 8.7, nilai p 0.045). Kesimpulan: Hipometilasi DNA gen CYP2C19 meningkatkan risiko terjadinya resistensi klopidogrel dan luaran klinis yang lebih buruk. ......Background: Clopidogrel resistance is an important risk factor of recurrence of ischemic event after optimal antiplatelet therapy. We aimed to investigate the role of DNA methylation of CYP2C19 gene as one of epigenetic factor to the risk of clopidogrel resistance in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). Methods: STEMI patients undergoing PPCI were pretreated with clopidogrel, and their platelet function was measured using VerifyNowTM assay. The criteria for high on- treatment platelet reactivity (HPR) was defined according to the expert consensus criteria (PRU >208). DNA methylation of the CYP2C19 gene was performed using bisulfite genomic sequencing technology. Furthermore, clinical, laboratory and angiographic data including TIMI flow were collected. Result: Among 122 patients, clopidogrel resistance was found in 22% patients. After dividing into two groups, methylation <50% was associated with increased risk of clopidogrel resistance (OR 4.5 95%CI 2.1-9.3, P value 0.018). This group also found to have suboptimal post-PCI TIMI flow (OR 3.4 95%CI 1.3 - 8.7, P value 0.045). Conclusions: The lower DNA methylation level of the CYP2C19 gene increases the risk of clopidogrel resistance and subsequent poorer clinical outcome.