Individualized Antiplatelet Therapy Under The Guidance Of MRNA Genetype Polymorphism In Patients With Acute Coronary Syndrome

Objective:Clopidogrel resistance(CR) increase the incidence of adverse cardiovascular events after coronary stent implantation,and CR is associated with CYP2C19 gene polymorphisms,but early adjustments of antiplatelet therapy in patients after percutaneous coronary intervention(PCI) according to gene polymorphisms to reduce cardiovascular adverse events is not clear. Our study aimed to investigate the influence of individualized antiplatelet therapy under the guidance of CYP2C19 polymorphism for adverse cardiovascular events, and thus provide more evidence-based data for clinical treatment.Methods: Patients in the Han population with acute coronary syndrome who accepted priamary or selective PCI in General Hospital of Chinese PLA Beijing Military Area Command from November 2013 to May 2014 were recruited in this study,and all patients were randomly divided into routine antiplatelet therapy group(RTG) and individualized antiplatelet therapy group(ITG) by 1:2 ratio.In RTG,patients received aspirin 100 mg/day plus clopidogrel 75 mg/day after stent implantation,the CYP2C19 gene was determined at the same time, but did not adjust drug according to the results.In ITG,patients were divided into LOF+group and LOF-group according to whether carried CYP2C19 Loss-of-the function(LOF) allele.In LOF+group, patients who carried CYP2C19 LOF allele(GA or AA genetype in any polymorphic of CYP2C19*2 or *3)received aspirin 100mg/day plus ticagrelor 90 mg twice daily after stent implantation,and in LOF-group, patients did not carried CYP2C19 LOF allele received aspirin 100 mg/day plus clopidogrel 75 mg/day after stent implantation.Followed-up 9~12month after PCI,the efficacy endpoint(major adverse cardiovascular events, stent thrombosis and recurrent angina) and safety index(bleeding) were observed in this period.Major adverse cardiovascular events include cardiovascular death,non-fatal MI,stroke and target vessel revascularization.Results: Finally, a total of 301 patients were enrolled,98 patients in RTG and 203 in ITG.37 patients were excluded(5 patients demanded end up the experiment,23 cases were lost to follow-up,9 patients due to the termination of dual antiplatelet drugs). 1 Basic characteristics between RTG and ITG Demographic and Clinical characteristics including age,gender,type of ACS(Unstable angina,acute non-ST segment elevation myocardial infarction,acute ST segment elevation myocardial infarction),risk factors(Smoking, diabetes, hypertension, dyslipidemia), comedications(stain,β-blocker,ACEI/ARB) and biochemicals(Fasting blood glucose,uric acid,creatinine,total cholesterol,triglycerides, high-density lipoprotein cholesterol,low density lipoprotein cholesterol, hemoglobin) did not differ between the 2 groups(all P>0.05). In addition to the number of patients with right coronary artery(62.2%vs46.3 %, P<0.05), coronary angiography data including lesions in left anterior descending artery,left circumflex artery,left main and single,double or multivessel lesions, number of stents,were no statistical significance between the 2 groups(all P > 0.05). 2 Comparison of the genotype and allele distribution of CYP2C19 in RTG and ITG 2.1 The CYP2C19*2 and CYP2C19*3 single nucleotide polymorphism loci was in Hardy-Weinberg equilibrium(P>0.05). 2.2 The genotype(GG/GA/AA) distribution of the CYP2C19*2 single nucleotide polymorphism loci including homozygous mutations(GG), heterozygous mutation(GA) and the wild type(AA) in RTG and ITG were no differences(all P> 0.05).The genotype(GG/GA) distribution of the CYP2C19 * 3 single nucleotide polymorphism loci including mutant heterozygote(GA) and the wild type(GG) in RTG and ITG were no differences(P>0.05).To analyze all patients,frequency of CYP2C19 * 2 A allele was 32.2% and CYP2C19 * 3 A allele was 4.0%. 3 Comparison of end point Followed-up 9~12month after PCI,the efficacy endpoint(major adverse cardiovascular events, stent thrombosis and recurrent angina) and safety index(bleeding) had no statistical difference(all P>0.05). 3.1 The RTG patients were analyzed retrospectively,patients who carried CYP2C19 LOF allele had a higer incidence of endpoint events(efficacy endpoint) than those who did not carried,but no statistically significant differences(all P > 0.05). 3.2 All patients who carried CYP2C19 LOF allele were analyzed retrospectively,the incidence of endpoint events in ticagrelor group were lower than clopidogrel group,but no statistically significant differences(all P> 0.05). 4 Other side effect of ticagrelor In all patients who received ticagrelor,15.3% of them with mild-to-moderate dyspnea,tardyarrhythmia occurred in 2.4% of them,but all patients were tolerated,did not need to adjust for ticagrelor. 5 Comparison of CYP2C19 genetype and thrombelastogram In patients who carried CYP2C19 LOF allele, the incidence of CR determined by thrombelastogram was 49.7%,and in other patients who did not carried CYP2C19 LOF allele,the incidence of CR determined by thrombelastogram was 46.0%.There was no correlation between CYP2C19 genetype and thrombelastogram(P>0.05).Conclusion:Individualized antiplatelet therapy under the guidance of CYP2C19 genetype polymorphism did not significantly reduce the incidence of endpoint events,but still need to further study confirmed.Patients who carried CYP2C19 LOF allele had a higher incidence of endpoint events than those who did not carried,and the incidence of endpoint events in ticagrelor group was lower than it in clopidogrel group,but but no statistically significant differences were observed,it still need to be investigated in large-scale study. There was no correlation between CYP2C19 genetype and thrombelastogram, according to the result of genetype to predictive the result of thrombelastogram maybe meaningfull.