Keywords : pharmacogenetics
Genetic Polymorphisms In Clopidogrel And Its Association With Adverse Cardiac Events After Coronary Intervention In Tertiary Care Centre From South India
European Journal of Molecular & Clinical Medicine,
2020, Volume 7, Issue 3, Pages 2390-2399
background: coronary artery disease is the leading cause of death in developing countries and the main treatment strategy includes pci which is usually followed by dual antiplatelet therapy (dapt) with aspirin and clopidogrel. Clopidogrel resistance from genetic polymorphisms incyp2c19 gene involved in hepatic activation of clopidogrel leads to clopidogrel nonresponsiveness and may result in increased adverse clinical outcomes. These polymorphisms in cyp2c19 gene and their impact in mace have been studied in southindian population only in limited number of studies.Methods:we studied 118 consecutive patients (mean age 55.7±10.7 years; 90% male) taking clopidogrel, with angiographically proven coronary artery disease for various genetic polymorphisms incyp2c19 gene. Relationship between loss of function mutation and clinical presentation with higher mace events including recurrent acute coronary syndromes, stent thrombosis were analyzed and genetic analysis. Results: out of 118 patients, 38 (32%) had normal genotype, 23 (20%) had loss offunction mutation( *2) the poor metabolizer type, and 57 (48%) had intermediate metabolizers (*2/*1). Final analyses included 118 patients, with 23 (20%) having loss of function. Seven patients developed stent thrombosis while on clopidogrel; all seven had loss of function mutationin cyp2c19 gene. 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. In patients with an acute myocardial infarction who were receiving clopidogrel, with cyp2c19 loss-of-function alleles had higher rate of subsequent major cardiovascular events in comparison with normal genotype individuals.