Association of Polymorphisms in CYP2C19 with the Efficacy of Clopidogrel Therapy in South Indian Patients Undergoing Percutaneous Coronary Intervention

Abstract

Background:The dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been considered as the standard of care in the setting of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). Recent evidence supports a role of loss-of-function (LOF) variants in the CYP2C19 as a determinant of clopidogrel response. Carriers of the CYP2C19*2 LOF allele has found to have the reduced pharmacodynamic response to clopidogrel and worse clinical outcome as compared with non-carriers in Asian countries including Indian population. However, it is unknown whether the time course of the antiplatelet effects of clopidogrel differs according to CYP2C19 genotype in South Indian patients with ACS. Methods: We assessed the platelet reactivity in the early and late phases of ACS according to CYP2C19 genotypes. Eighty six consecutive in-patients who were admitted with ACS at our center were enrolled in the study. The determination of platelet aggregation was done by using a platelet aggregometer and genetic analysis was done by PCR-RFLP method. Results: The numbers of patients carrying the CYP2C19*1/*1 (extensive metabolizer, EM), *1/*2 (Intermediate metabolizer, IM), *2/*2 (poor metabolizer PM), genotypes were 22 (30.9%), 37 (52.1%), 12 (16.9%), respectively. Time course of platelet aggregation from baseline to the late phase among the 3 genotypes indicate that there was statistically significant at 30 th day of treatment (p=0.004) between wild versus hetero and homozygous variant alleles. The percentage of patients shifted to prasugrel from clopidogrel due to non-response were 4 (8%), 11(29%), 6 (50%) in wild, heterozygous and homozygous variant alleles. In homozygous group, we found 4 out of 6 patients developed acute stent thrombosis within one week of PCI. Conclusion: We observed that the CYP2C19*2 and CYP2C19*1/*2 are the major determinants of clopidogrel efficacy. Acute stent thrombosis was observed in patients carrying CYP2C19*2 variant allele

Polimorfisme Cyp2c19*2 Terhadap Agregasi Platelet Dan Kejadian Kardiovaskular Pada Pasien Penyakit Jantung Koroner

“…(8,11) Studi lain, meta analisis dari Jae sik Jang et al, (2012) (11) Beberapa studi yang telah disebutkan menunjukkan bahwa polimorfisme CYP2C19*2 sebagai LOF alel memang kerap kali terbukti telah menjadi variant alel yang paling sering mengakibatkan MACE. (13) Studi terbaru dari Kumari et al,(2017) juga menyatakan adanya kejadian kardiovaskular pada pasien PJK yang mengalami thrombosis dan diikuti pemasangan ring (Acute Stent Thrombosis). Kejadian kardiovaskular tersebut juga dipicu oleh adanya polimorfisme CYP2C19*2.…”

“…Kejadian kardiovaskular tersebut juga dipicu oleh adanya polimorfisme CYP2C19*2. (14) Keterkaitan antara polimorfisme genetik CYP2C19*2 dengan tingkat terjadinya agregasi antiplatelet, didukung pada penelitian Liu et al (2016) yang melakukan pengukuran dengan menggunakan Light Transmission Aggregometry, dikatakan bahwa CYP2C19 memegang peranan penting pada dua tahap proses oksidasi metabolit di hati, sehingga dapat mempengaruhi seberapa besar antiplatelet dapat bekerja. (12) Berdasarkan studi penelitian polimorfisme genetik terkait bidang farmakogenomik perlu dilakukan guna mengamati adanya perbedaan respon dari setiap individu terhadap obat yang diberikan.…”

“…( 16)( 23)- (24) Selain itu pada studi Kumari et al (2017), menyebutkan bahwa terdapat penggantian obat klopidogrel sebanyak 50% pada tipe homozigot, digantikan ke prasugrel akibat ditemukannya resistensi klopidogrel. (14)…”