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Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel was treatment for ACS or for patients undergoing PCI. Clopidogrel is a pro-drug that must be metabolized by the cytochrome P (CYP) 450 enzyme system to generate active metabolites. Metabolic activation by CYP2C19 is crucial for generation of such metabolites. Several gene variants are associated with reduced or enhanced CYP2C19 activity, however, CYP2C19*2 and CYP2C19*3 are the major mutant alleles of CYP2C19 that account for >99% of loss-of-function (LOF) alleles in Asian populations.
86 consecutive in-patients who were admitted with acute coronary syndrome were enrolled. Out of 86 patients, the data of 71 patients was finally analysed. Platelet aggregometer (Chronolog) was used for the platelet aggregation test and CYP2C19 phenotype was determined PCR-RFLP method. Follow-up visits were conducted for at least 4 weeks. Categorical variables are expressed as percentages and mean ± SD were compared by the chi-square test. Values of p < 0.05 were considered significant. Allele frequencies were calculated, and departure from Hardy-Weinberg equilibrium was tested by the chi-square test.
Platelet reactivity was serially assessed,CYP2C19 genotypes were determined in 71 patients with ACS who underwent stent implantation and received aspirin and clopidogrel. The numbers of patients carrying the CYP2C19*1/*1, *1/*2, *2/*2, genotypes were 22 (30.9%), 37(52.1%), 12 (16.9%), respectively. Time course of percentage of platelet aggregation inhibition was measured at baseline, 7, 15- 30 days of aspirin and clopidogrel treatment. Platelet aggregation inhibition levels at baseline were similar among 3 phenotypes [53 ± 25 (95%CI: 41.82-64.09), 71 ± 20 (95%CI: 64.08-77.75), 72 ± 34(95%CI: 56.31-86.87)] respectively. Time course of platelet aggregation inhibition from baseline to 1 week among the 3 phenotypes indicate that there was no statistically significant (p=0.12) platelet aggregation inhibition among 3 phenotypes at 1week were [19 ± 17 (CI 11.31 - 26.42), 29.20 ± 20 (CI 22.52 - 36.13), 29 ± 19 (CI 16.7 - 41.4)] respectively, whereas at 15 to 30 days (p < 0.004) of treatment, there was statistically significant platelet aggregation inhibition, 16.59 ± 14.98 (95%CI: 9.95 - 23.23), 32.7 ± 17.46 (95%CI: 26.88-58.5), 31.75 ± 19.79 (95%CI: 19.18-44.5) respectively. The effect of CY2C19 polymorphism on platelet aggregation is increased at 15 - 30 days of clopidogrel and aspirin treatment. During the follow up period, the percentage of patients shifted to prasugrel or ticagrelor from clopidogrel due to non-response were 4 (8%), 11(29%), 6 (50%) in wild, heterozygous, homozygous variant alleles respectively, 4 out of 6 patients developed acute stent thrombosis within 1 week in patients carrying homozygous variant.
To conclude, the results of our study 50% of the study population with ACS carry CYP2C191*2* variant alleles. The majority of IM and PM has increased platelet reactivity during early and intermediate stages of ACS.