Hasil Pencarian  ::  Simpan CSV :: Kembali

"ABSTRAKLatar Belakang. Pada penderita APTS/IMA-NEST, agregasi platelet dianggapsebagai faktor penyebab kejadian trombosis dan disfungsi mikrosirkulasi melaluimekanisme embolisasi distal. Pemeriksaan fungsi platelet berperan dalam menilaiderajat inhibisi platelet oleh pemberian antiplatelet khususnya clopidogrel.Tujuan. Menilai hubungan antara reaktivitas platelet dalam terapi clopidogrealdengan kejadian obstruksi mikrovaskular pada penderita APTS/IMA-NEST.Metode. Penelitian potong lintang dilakukan untuk menilai hubungan reaktivitasplatelet pada terapi clopidogrel dengan kejadian obstruksi mikrovaskular padapenderita APTS/IMA-NEST yang menjalani tindakan intervensi perkutan.Pengukuran nilai reaktivitas platelet dilakukan sebelum tindakan IKP minimal 6jam pasca loading dose clopidogrel 300 mg. Penilaian obstruksi mikrovaskulardiukur dengan myocardial blush grade (MBG) setelah intervensi koronerperkutan.Hasil. Total sebanyak 96 orang pasien yang memenuhi kriteria inklusi penelitianselama periode Mei-Oktober 2012. Sebanyak 21 subjek (21.9%) dikategorikansebagai non responder dengan nilai reaktivitas platelet ≥ 47 U, sementarasebanyak 75 subjek (78.1%) dikategorikan sebagai responder (< 47U). Reratanilai reaktivitas platelet pada kelompok non responder 63.8±18.4 U berbanding28.3±10.34 U pada kelompok responder (p=0.000). Berdasarkan nilai myocardialblush grade, kelompok subjek dengan nilai MBG 0-1 ditemukan sebanyak 12subjek (12.5%) sementara kelompok subjek dengan nilai MBG 2-3 sebanyak 84subjek (87.5%) dengan rerata nilai reaktivitas platelet 47±26.3 U berbanding35.5±19.6 U (p=0.00). Terdapat perbedaan antara kedua kelompok terhadap skorGRACE ≥ 140 (75% vs 89,3%,p=0.17), tipe lesi ACC/AHA (58,4% vs33.4%,p=0.11), aliran TIMI (50% vs 2.3%, p=0.000), dan jumlah non responder (58.3%vs 16.6%, p=0.004). Melalui analisis multivariat, nilai reaktivitas platelet padaterapi clopidogrel memiliki hubungan dengan kejadian obstruksi mikrovaskulardengan odds ratio (OR) 6.8 (IK 95%:1,8-25.4, p=0.004).Kesimpulan. Terdapat hubungan antara nilai reaktivitas platelet pada terapiclopidogrel dengan kejadian obstruksi mikrovaskular pada penderita IMA-NESTyang menjalani tindakan IKP dalam masa perawatan di rumah sakit.

---

ABSTRACTBackground. In the setting of UA/NSTEMI, platelet aggregation has a pivotalrole in trombosis and microcirculation dysfunction resulting from distalembolization, and the rate of microcirculation dysfunction will increase byiatrogenic plaque rupture during PCI. Platelet function tests has been widely usedto measure platelet inhibition level on antiplatelet therapy, particularly onclopidogrel.Objective. This study aimed to evaluate the association between plateletreactivity on clopidogrel treatment with microvascular obstruction after PCI inUA/NSTEMI patients.Method. A cross sectional study was conducted to evaluate the associationbetween platelet reactivity on clopidogrel treatment and microcvascularobstruction after PCI in UA/NSTEMI patients. Platelet reactivity was measuredbefore PCI minimal 6 hours after loading dose 300 mg clopidogrel, whilemicrovascular obstruction was evaluated by myocardial blush grade (MBG).Results. Out of 96 subjects examined during May to October 2012, 21 subjects(21.9%) was categorised as non responder (≥47 U) and 75 subjects (78.1%) asresponder (<47 U). Mean platelet reactivity in non responder group was 63.8±18.4U versus 28.3±10.34 U in responder group (p=0.000). Based on myocardialblush, MBG 0-1 was found in 12 subjects (12.5%) while MBG 2-3 was found in84 subjects (87.5%). There were difference in both groups on GRACE risk score≥ 140 (75% vs 89,3%,p=0.17), ACC/AHA type lesion (58,4% vs33.4%, p=0.11),TIMI flow (50% vs 2.3%, p=0.000), and number of responder subjects (58.3% vs16.6%, p=0.004) with mean platelet reactivity 47±26.3 U vs 35.5±19.6 U,respectively (p=0.00). Multivariate analysis showed that platelet reactivity onclopidogrel treatment is persistently associated with microvascular obstruction(OR 6.8, CI: 1,8-25.4, p=0.004).Conclusion. In this study, platelet reactivity on clopidogrel treatment isassociated with microvascular obstruction after stenting in UA/NSTEMI patients."

"Latar Belakang: Disfungsi mikrovaskular merupakan salah satu manifestasi cedera reperfusi letal. Ticagrelor diketahui memiliki efek kardioprotektif terhadap cedera reperfusi pada hewan coba. Efeknya pada manusia masih harus dibuktikan terutama terhadap perfusi mikrovaskular koroner. Tujuan: Mengetahui efek ticagrelor terhadap perfusi mikrovaskular koroner pada pasien infark miokard akut dengan elevasi segmen ST IMA-EST yang menjalani intervensi koroner perkutan primer IKPP. Metode: Penelitian ini merupakan studi eksperimental acak tersamar ganda yang dilakukan di Rumah Sakit Jantung dan Pembuluh Darah Harapan Kita pada bulan Agustus 2016 sampai November 2016. Pasien IMA-EST yang akan dilakukan IKPP dirandomisasi ke dalam dua kelompok yaitu kelompok yang mendapatkan ticagrelor dan yang mendapatkan clopidogrel sebelum IKPP. Dilakukan pemeriksaan myocardial blush kuantitatif dengan menggunakan program Quantitative Blush Evaluator QuBE. Hasil Penelitian: Terdapat total 40 subyek, 20 subyek kelompok ticagrelor dan 20 subyek kelompok clopidogrel. Tidak ditemukan perbedaan bermakna antara kelompok ticagrelor dengan clopidogrel terhadap nilai myocardial blush kuantitatif dengan QuBE 18,8 6,6-33,6 vs 18,1 12,4-32,3 , nilai p 0,978. Kesimpulan: Tidak terdapat perbedaan nilai myocardial blush kuantitatif pada pemberian ticagrelor sebelum IKPP pada pasien IMA-EST yang menjalani revaskularisasi bila dibandingkan dengan pemberian clopidogrel sebelum IKPP.

---

Background: Microvascular dysfunction become one of lethal reperfusion injury manifestation. Ticagrelor known having cardioprotective effect against reperfusion injury in animal trial. It effects in human need further investigation and evidence.

Objective: To determine the effect of ticagrelor on coronary microvascular perfusion in acute ST elevation myocardial infarction STEMI patients underwent primary percutaneous coronary intervention PPCI.

Method: This was a double blind randomized clinical trial conducted in National Cardiovascular Center Harapan Kita from August to November 2016. Acute ST elevation myocardial infarction patients underwent PPCI were randomized into two groups, ticagrelor or clopidogrel loading dose before PPCI. Quantitative myocardial blush score was assessed after PPCI using Quantitative Blush Evaluator QuBE program.

Result: There were 40 subjects included in this trial, 20 subjects in ticagrelor group and 20 subjects in clopidogrel group. There was no significant difference between two groups regarding the QuBE score 18,8 6,6 33,6 vs 18,1 12,4 32,3 , nilai p 0,978.

Conclusion: There is no difference on quantitative myocardial blush score in STEMI patient given ticagrelor before PPCI compare to clopidogrel. "

"Intervensi Koroner Perkutan Primer (IKPP) merupakan pilihan utama untuk mengembalikan aliran darah dan perfusi pasien yang mengalami Infark Miokard Akut dengan Elevasi Segmen ST (IMA-EST). Tapi tidak selalu mengembalikan aliran yang cukup pada tingkat mikrosirkulasi, hal ini disebabkan oleh obstruksi mikrovaskular (OMV). Banyak penelitian telah membuktikan pengaruh inflamasi terhadap kejadian OMV, tingginya rasio neutrofil limfosit pasca IKPP menggambarkan respon inflamasi. Tujuan penelitian ini adalah untuk menilai hubungan rasio neutrofil limfosit (RNL) terhadap kejadian obstruksi mikrovaskular yang dinilai dengan pemeriksaan myocardial blush kuantitatif (QuBE). Metode: Sebanyak 33 subjek IMA–EST yang menjalani IKPP dipilih secara konsekutif sejak 1 September 2013 sampai 30 Oktober 2013. RNL diambil saat masuk UGD, penilaian myocardial blush (MB) diambil segera pasca IKPP, angiografi untuk RCA (RAO 30˚) dan LCA (LAO 60˚-90˚). Kemudian RNL dikirim ke laboratorium untuk diperiksa dengan dengan Sysmex 2000i, blush dinilai dengan program komputer QuBE. Perhitungan statistik dinilai dengan SPSS 17. Hasil: Dari 33 pasien didapatkan proporsi terbanyak berjenis kelamin laki-laki sebesar 75,7%, rerata usia pasien 56±9.8 tahun. Analisa statistik menunjukkan tidak terdapat hubungan antara RNL dan QuBE (β=-0,180;p=0,664) namun terdapat kecenderungan setiap kenaikan 1 unit RNL akan menurunkan QuBE sebesar 0,180 unit arbiter. Setelah dilakukan adjusted terhadap faktor perancu didapatkan kecenderungan penurunan yang lebih besar meskipun tetap tidak menunjukkan hubungan yang bermakna. (koef β=-0,331 ; p=0,527).

---

Primary percutaneus coronary intervention (PPCI) is a first of choice to return patient’s blood flow and perfusion with ST elevation myocardial infarction (STEMI). However, it is not always sufficiently reflow of microcirculation due to Microvascular Obstruction (MVO). Many studies had proved that neutrophil to lymphocyte ratio (NLR) has emerged as a potent composite inflammatory marker. The aim of this study is to evaluate association between NLR and MVO by Quantitative Blush Evaluator (QuBE).

Methode: 33 STEMI patients undergoing primary PCI were consecutivly recruited from September to October 2013. The NLR was withdraw at patient admission. We evaluate the myocardial blush immediately after PCI done. Angiography views were RAO 30˚ for RCA, and LAO 60˚-90˚for LCA. Then the NLR was sent to laboratory for examination. QuBE was done to evaluate myocardial blush. Statistical analysis was done by SPSS 17.

Results: From thirty three patients included in the study, there were 75,75% men, with mean age 56±9.8 years old. Statistical analysis showed no correlation between NLR and QuBE (β=-0,180;p=0,664) but there was decrease of 0,180 unit arbiter QuBE for each 1 unit of peripheral NLR. After adjustment of confounding factor, there was more decreasing value although there is no significant correlation. (coef β=-0,331;p=0,527)."

"Latar belakang: micro-RNA saat ini telah diketahui berperan dalam patofisiologi berbagai penyakit termasuk di bidang kardiovaskular. miR-26a platelet dikaitkan dengan aktifitas platelet tinggi.Resistensi klopidogrel telah diketahui memiliki prevalensi yang cukup tinggi di populasi Asia, yang mana dapat mempengaruhi mortalitas serta kejadian kardiovaskular mayor. Hubungan antara ekspresi miR-26a platelet dengan resistensi klopidogrel begitu pula dengan TIMI flow pasca IKPP pada IMA-EST di populasi Asia, belum pernah dilaporkan. Tujuan: Penelitian ini bertujuan untuk mengetahui hubungan antara ekspresi miR-26a platelet terhadap reaktivitas platelet dan perfusi miokardium pasca IKPP. Metode: Pada pasien IMA-EST yang menjalani IKPP dan mendapatkan terapi dosis loadingklopidogrel 600 mg, dimasukkan kedalam populasi penelitian. Kami mengukur reaktivitas platelet dengan menggunakan VerifyNow P2Y12, aktifitas platelet tinggi didefiniskan jika memiliki nilai > 208 PRU. Metode RealtimePCR Taqman dilakukan untuk analisa ekspresi miR-26a platelet. Ekspresi miR-26a platelet dan reaktivitas platelet dikorelasikan dengan TIMI flowpasca IKPP pada pasien IMA-EST. Hasil: Terdapat 100 subyek yang direkrut pada studi ini. Diantaranya, 59% menunjukkan peningkatan ekspresi miR-26a. Reaktifitas platelet meningkat pada 27 % pasien studi ini dikategorikan non-responder terhadap klopidogrel. Terdapat hubungan antara ekspresi dengan penurunan fungsi penghambatan platelet (OR 4.2, p = 0.006). Indeks reaktivitas platelet >208 PRU meningkatkan risiko TIMI flow < 3 (OR 3.3, p= 0.015). Tidak terdapat hubungan langsung antara ekspresi miR-26a platelet dan TIMI flow < 3. Kesimpulan: Pasien dengan peningkatan ekspresi miR-26a platelet memiliki risiko untuk mengalami menjadi non-responderklopidogrel. Tidak terdapat hubungan langsung antara ekspresi miR-26a platelet dan TIM flowpasca IKPP.

---

Background: micro-RNA has now been known to play a role in the pathophysiology of various diseases including cardiovascular disease. Clopidogrel resistance has been known prevalent in Asian population, that may affect mortality and major cardiovascular events. The relationship between the expression of platelet miR-26a and clopidogrel resistance as well as TIMI flow post primary PCI in STEMI among Asian populations, has never been done.

Objective: the aim of this study is to define whether miR-26a platelet expression has a relation with platelet reactivity and myocardial perfusion after primary PCI.

Methods: STEMI patients who underwent primary PCI and has received 600 mg loading dose of clopidogrel were recruited for the study. We measured platelet reactivity by VerifyNow P2Y12, high platelet reactivity was defined as > 208 PRU. Realtime PCR by taqman method were performed to asses the expression of miR-26a platelet. miRNA-26a platelet expression and platelet reactivity were correlated with TIMI flow post primary PCI in STEMI.

Hasil: there were 100 patients recruited for this study. among them, 59% of patients with high expression of miR-26a platelet. Platelet reactivity showed 27% of the patients were clopidogrel non-responders. There was a relationship between high miR-26a expression and decreased function of platelet inhibition (OR 4.2, p = 0.006). Platelet reactivity index > 208 increased the risk of suboptimal reperfusion (OR 3.3, p = 0.015). There was no direct correlation between miR-26a expression and TIMI flow < 3.

Conclusion: Patients with high miR-26a platelet expression had increased risk of being clopidogrel non responders. There is no direct relationship between miR-26a platelet expression and TIMI flow after primary PCI."

"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."

"Latar belakang. Kemajuan terapi reperfusi pada pasien infark miokard akut menimbulkan satu fenomena yang turut berperan dalam prognosis pasien, yaitu fenomena no reflow atau obstruksi mikrovaskular. Mekanisme OMV diduga memiliki 4 komponen patogenik utama yaitu embolisasi distal aterotrombotik, cedera reperfusi, cedera iskemia, dan kerentanan individu. Hiperglikemia akut diketahui berhubungan dengan OMV pada pasien IMA, namun peran hiperglikemia kronik masih kontroversial. Hiperglikemia berperan dalam komponen kerentanan individu, serta mempengaruhi peningkatan faktor inflamasi yang berperan dalam komponen cedera reperfusi. Kedua faktor ini yaitu hiperglikemia kronik yang digambarkan HbA1C dan inflamasi yang digambarkan hsCRP belum pernah diteliti secara bersamaan dalam menilai OMV dengan satu metode. Penelitian ini akan meneliti hubungan antara HbA1C dan hsCRP dengan OMV yang dinilai menggunakan indeks resistensi mikrovaskular, suatu metode terbaru dalam menilai OMV dengan akurat pada fase awal dan memiliki nilai prognostik yang signifikan. Metode. Sebanyak 55 pasien IMA-EST yang menjalani IKPP dipilih secara konsekutif sejak Januari-Juni 2014. HbA1C dan hsCRP diambil saat masuk UGD, penilaian IMR diambil segera setelah tindakan IKPP. Perhitungan statistik menggunakan SPSS 17. Hasil. Dari 55 pasien didapatkan proporsi laki-laki sebesar 93%, dengan rerata umur 51,91 ± 8,87 tahun. Faktor resiko penyakit jantung koroner terbanyak adalah merokok yaitu 69%. Semua pasien menjalani tindakan IKPP dengan waktu iskemia 489,45±169,95 menit dan waktu perfusi 124,91±76,49 menit. Nilai rerata IRM 53,22±41,11 dengan nilai rerata HbA1C 6,46±1,22 %, dan rerata hsCRP 4,98±3,39 mg/dL. Dari analisis bivariat didapatkan HbA1C tidak berhubungan dengan IRM (r=0,22,p=0,10), dan hsCRP juga tidak berhubungan dengan IRM (r=0,24,p=0,08). Setelah disesuaikan dengan variabel perancu pada analisis multivariat, didapatkan hubungan signifikan antara HbA1C dengan IRM (p=0,03) namun hsCRP tidak berhubungan dengan IRM (p=0,31). Kesimpulan. Kadar HbA1C saat admisi berhubungan dengan IRM pada pasien IMA-EST yang menjalani IKPP dan hsCRP saat admisi tidak berhubungan dengan IRM pasien IMA-EST yang menjalani IKPP.

---

Background: Advances in reperfusion therapy for acute myocardial infarction led to a phenomenon of distal no reflow or myocardial obstruction (MVO), which associated with worse outcome and prognosis. The potential mechanism of MVO had four major pathogenic components: distal atherotrombotic embolization, reperfusion injury, ischemic injury, and individual susceptibility. Association between acute hyperglycemia and MVO in acute myocardial infarction has been found, but the role of chronic hyperglycemia remained controversial. Hyperglycemia affected individual susceptibility to microcirculatory injury, and also induced systemic inflammation which had a role in reperfusion injury. Association of both these factors--chronic hyperglycemia, determined by Hemoglobin A1C, and inflammation factor, measured by high sensitivity C-Reactive Protein-- with MVO had never been studied simultaneously. This cross-sectional study will determine the association between HbA1C and hsCRP with MVO assessed with index of microvascular resistance, an invasive novel method to assess MVO in acute phase and had significant prognostic factor.

Methods: 55 patients with acute ST-elevation myocardial infarction underwent primary percutaneous coronary intervention were taken consecutively from January to June 2014. Blood samples for HbA1C and hsCRP were taken before the procedure. IMR was taken immediately after the primary percutaneous coronary intervention procedure. Statistical calculation used SPSS 17.

Results: From 55 patients included in the study, there were 93% men, with mean age of 51.91 ± 8.87 years. The most common risk factors for coronary heart disease was smoking (69%). All patients underwent primary percutaneous coronary intervention with mean onset to balloon time was 489.45 ± 169.95 minutes and mean door to balloon time was 124.91 ± 76.49 minutes. Mean IMR was 53.22 ± 41.11, with mean HbA1c was 6.46 ± 1.22% and mean hsCRP was 4.98 ± 3.39 mg/dL . From bivariate analysis, there was no association between HbA1C and IMR (r=0,22, p = 0,10), and between hsCRP and IMR (r = 0,24 , p=0,08). In multivariate analysis , there was relationship between HbA1C with IRM ( p = 0,03) and hsCRP were also not associated with IRM ( p = 0,31 ).

Conclusions. There was association between hemoglobin A1C levels on admission with IMR and no association between hsCRP levels on admission with IMR, in patients with acute ST-elevation myocardial infarction underwent primary percutaneous coronary intervention."

"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."

"ABSTRAKLatar belakang: Salah satu faktor yang dicurigai berperan dalam mekanisme resisensi klopidogrel adalah faktor epigenetik seperti metilasi DNA. Individu dengan resistensi klopidogrel ini memiliki kecenderungan untuk mengalami luaran kardiovaskular yang lebih buruk. Nilai TIMI flow pasca IKPP telah diketahui berkaitan dengan luaran klinis pada pasien IMA-EST. Sampai saat ini belum ada penelitian yang menghubungan antara metilasi gen P2Y12 dengan penghambatan fungsi platelet dan nilai TIMI flow pasca IKPP pada pasien IMA EST. Tujuan: Untuk mengetahui hubungan antara metilasi gen reseptor P2Y12 terhadap fungsi penghambatan platelet dan nilai TIMI flow pasca IKPP pada pasien IMA EST. Metode: Sebanyak 118 pasien IMA-EST yang menjalani IKPP dan mendapatkan terapi klopidogrel dimasukkan kedalam populasi penelitian. Dilakukan pemeriksaan VerifyNow P2Y12 dan pemeriksaan metilasi P2Y12. Selanjutnya dilakukan analisis hubungan antara metilasi P2Y12 dengan nilai Verifynow P2Y12 dan TIMI flow pasca IKPP. Hasil: Dari seluruh subyek, 22% diantaranya termasuk klopidogrel nonresponder dan 30% memiliki nilai TIMI flow kurang dari 3. Terdapat 48% subyek yang tidak mengalami metilasi dan 19% subyek mengalami metilasi sempurna pada gen P2Y12. Tidak terdapat hubungan bermakna antara metilasi P2Y12 dengan nilai Verifynow P2Y12 dan TIMI flow pasca IKPP. Nilai Verifynow P2Y12 yang tinggi berhubungan dengan TIMI flow kurang dari 3 pasca IKPP (p=0,043). Kesimpulan: Tidak terdapat hubungan bermakna antara pola metilasi gen P2Y12 dengan penghambatan fungsi platelet dan nilai TIMI flow pasca IKPP. Pasien yangnon-responder terhadap klopidogrel berisiko untuk mendapatkan reperfusi miokard yang suboptimal.

---

ABSTRACTBackground: Mechanism of clopidogrel resistance is not well understood yet. In the other hand, epigenetic modifications such as DNA methylation, are suspected to play role in clopidogrel resistence. Subject with high on treatment clopidogrel reactivity show worsen cardiovascular outcome. Meanwhile, TIMI flow after reperfusion are known to be related with poor outcome. Study that evaluate the relationship between methylation of P2Y12 gene with Platelet Reactivity and TIMI-flow after Primary Percutaneous Coronary Intervention (PPCI) in Patients With Acute ST-segment Elevation Myocardial Infarction in South East Asia Population has never been done. Objectives: to define whether methylation of P2Y12 gene and platelet reactivity may affect the myocardial perfusion after PPCI. Methods: There were 118 of STEMI patients who underwent PPCI and had received clopidogrel were recruited for the study. We measured platelet reactivity using Verifynow P2Y12 and Methylation of P2Y12 gene. The relationship among variables are assessed using statistic method. Results: Among 118 subject, 22% are clopidogrel nonresponder and 30% had TIMI flow less than 3. Median of Methylation degree was 15% with 48% subject were unmethylated, 19% subject had 100% methylation. There are no relationship between methylation of P2Y12 gene with platelet reactivity and TIMI flow after PPCI among subjects. The value of Verifynow P2Y12 more than 208 were related TIMI flow less than 3 after PPCI (p=0,043). Conclusion: There are no relationship between methylation of P2Y12 gene with platelet reactivity and TIMI flow after PPCI among subjects. Clopidogel nonresponder subjects were more likely to have suboptimal reperfusion after PPCI"

"Latar belakang: Polimorfisme genetik dari reseptor P2Y12 dikatakan dapatmempengaruhi aktivasi reseptor P2Y12 atau menghambat aktivasi trombosit. Beberapapolimorfisme nukleotida tunggal dalam gen P2Y12 ditemukan dapat menyebabkanvariabilitas antarindividu dalam agregasi platelet. Telah diidentifikasi limapolimorfisme dari gen P2Y12 yaitu T744C, C34T, G52T, ins801A, dan C139T. Salahsatunya, polimorfisme C34T adalah salah satu dari polimorfisme yang dikatakan adakaitannya dengan peningkatan agregasi platelet yang dapat menunjukkan kemungkinanuntuk terjadinya modifikasi respon terapi clopidogrel. Namun hingga saat ini belumada penelitian yang menilai hubungan langsung antara polimorfisme reseptor P2Y12dengan TIMI-flow beserta faktor-faktor yang mempengaruhinya, termasuk fungsipenghambatan platelet pada pasien IMA-EST yang menjalani IKPP.Tujuan: Penelitian ini bertujuan untuk mengetahui hubungan antara polimorfismenukleotida tunggal pada reseptor P2Y12 dengan TIMI flow beserta faktor-faktor yangmempengaruhinya, termasuk penghambatan fungsi platelet.Metode: Studi potong lintang pada 167 pasien IMA-EST yang menjalani IKPP.dilakukan pemeriksaan polimorfisme C34T reseptor P2Y12 dengan metode Taqmandan pemeriksaan fungsi penghambatan platelet yang diukur dengan VerifyNow P2Y12.Hasil: Dari 167 subjek penelitian, studi polimorfisme mengungkapkan proporsi pasiendengan heterozygous mutan sebanyak 34.1%, dan 1.8% pasien merupakan homozygousmutan. Sisanya adalah homozygous wildtype ditemukan sebanyak 64.1%. 25.7% pasientergolong non-responder terhadap clopidogrel. Secara keseluruhan tidak terdapathubungan secara langsung antara polimorfisme C34T dengan TIMI flow < 3, namunterdapat hubungan antara polimorfisme C34T dengan penurunan fungsi penghambatanplatelet (OR 2.17, p = 0.046).Kesimpulan: Tidak terdapat hubungan secara langsung antara polimorfisme C34Tdengan TIMI flow, namun pasien dengan polimorfisme C34T pada reseptor P2Y12memiliki risiko untuk mengalami penurunan penghambatan fungsi platelet.

---

Background: Genetic polymorphism of P2Y12 receptors is said to have affect of

P2Y12 receptor activation or inhibit platelet activation. Several single nucleotide

polymorphisms in the P2Y12 gene were found to cause variability between individuals

in platelet aggregation. Five polymorphisms have been identified from the P2Y12 gene,

namely T744C, C34T, G52T, ins801A, and C139T. One of them, C34T is one of the

polymorphisms that is said to be related to increased platelet aggregation which can

indicate the possibility for modification of the response of clopidogrel therapy. But until

now there has been no research that assesses the direct relationship between P2Y12

receptor polymorphisms and TIMI-flow along with the factors that influence it,

including the function of platelet inhibition in STEMI patients undergoing PPCI

Objective: This study aims to determine the relationship between single nucleotide

polymorphisms at P2Y12 receptors with TIMI flow along with the faktors that

influenced it, including inhibition of platelet function.

Methods: A cross-sectional study of 167 STEMI patients who underwent PPCI. C34T

polymorphism of P2Y12 receptor was evaluated by the Taqman method and the

inhibition of platelet function was measured by VerifyNow P2Y12.

Results: Among 167 subjects, the heterozygous mutants group were 34.1%, and 1.8%

of patients were homozygous mutants. The rest 64.1% was homozygous wildtype.

25.7% of patients were classified as non-responders to clopidogrel. Overall there was

no direct relationship between C34T polymorphisms and TIMI flow <3, but there was

a relationship between C34T polymorphisms and decreased platelet inhibitory function

(OR 2.17, p = 0.046).

Conclusion: There is no direct relationship between C34T polymorphisms and TIMI

flow, but patients with C34T polymorphisms of P2Y12 receptors have a risk of

decreasing platelet function inhibition."

"Polimorfisme CYP2C19 menurunkan metabolisme klopidogrel dan telah diketahui meningkatkan mortalitas serta kejadian kardiovaskular mayor. VerifyNow P2Y12 merupakan salah satu pemeriksaan yang secara spesifik menggambarkan fungsi platelet terhadap agen penghambat P2Y12 yang dikonsumsi. Hubungan antara polimorfisme CYP2C19 dengan TIMI flow pada populasi Asia, khususnya Indonesia, belum pernah dilakukan.Penelitian ini bertujuan untuk mengetahui hubungan antara polimorfisme CYP2C19 terhadap fungsi penghambatan platelet dan TIMI flow, serta hubungan antara fungsi penghambatan platelet dan TIMI flow.Dilakukan pemeriksaan polimorfisme CYP2C19 dengan menggunakan metode Taqman dan pemeriksaan fungsi penghambatan platelet yang diukur dengan VerifyNow P2Y12 pada 90 pasien IMA-EST yang menjalani IKPP yang memenuhi kriteria penelitian.Dari 90 subyek penelitian, studi polimorfisme genetik mengungkapkan 23,3% pasien dengan alel * 2, 11,2% dari * 3 alel pembawa, dan 1,1% membawa kedua alel. 24,4% pasien tergolong non-responder terhadap klopidogrel. Secara keseluruhan tidak terdapat hubungan secara langsung antara polimorfisme CYP2C19 dengan TIMI flow 3, namun terdapat hubungan antara polimorfisme CYP2C19 dengan penurunan fungsi penghambatan platelet (OR 4.7, p = 0.030). Indeks reaktivitas platelet >208 PRU meningkatkan risiko TIMI flow < 3 (OR 3.3, p= 0.046).Tidak terdapat hubungan secara langsung antara polimorfisme CYP2C19 dengan TIMI flow, namun pasien dengan polimorfisme CYP2C19*2 dan/atau *3 memiliki risiko untuk mengalami penurunan penghambatan fungsi platelet. Pasien yang tergolong non-responder terhadap klopidogrel ini juga berisiko untuk mendapatkan reperfusi miokard yang suboptimal.

---

CYP2C19 polymorphism plays an important role in clopidogrel metabolism. The genetic factor is VerifyNow P2Y12 is an examination that specifically describes platelet function against P2Y12 inhibitors. It is unknown whether platelet reactivity measured by P2Y12 reaction unit (PRU) is affected by CYP2C19 polymorphism or predictive of TIMI flow in Asian populations, particularly in Indonesia. We sought to define whether polymorphisms on CYP2C19 genes and platelet reactivity may affect the myocardial perfusion.

STEMI patients who underwent primary PCI and has received 600 mg loading dose of clopidogrel were recruited for the study. We measured platelet reactivity by VerifyNow P2Y12, high platelet reactivity was defined as > 208 PRU. Genetic polymorphisms analysis to assess the presence of CYP2C19*2 and *3 alleles on each patient were performed by Taqman method.

There were 90 patients recruited for study. Genetic polymorphisms studies revealed 23.3% of patients with *2 allele, 11.2% of *3 allele carriers, and 1.1% carried both allele. 23.4% of patients were clopidogrel non-responders. Overall, there was no correlation between CYP2C19 polymorphism and TIMI flow < 3, but there was a relationship between CYP2C19 polymorphism and decreased function of platelet inhibition (OR 4.7, p = 0.030). Platelet reactivity index > 208 increased the risk of suboptimal reperfusion (OR 3.3, p = 0.046).

There is no direct relationship between CYP2C19 polymorphism and TIMI flow, but patients with CYP2C19*2 and/or CYP2C19*3 had increased risk of being clopidogrel non responders. After adjusted to confounding factors, VerifyNow > 208 PRU is associated with suboptimal myocardial reperfusion."