Effects Of Different PPIs And Loss Of Function CYP2C19Alleles On CHD Patients

Clopidogrel co-administered with aspirin have become a corner-stone in treatment of ACS and PCI patients. Given the increased bleeding risk associated with antiplatelet therapy, PPIs are prescribed oiten.Clopidogrel and PPIs have a pharmacodynamie interaction because they are both metabolited by CYP2C19.CYP2C19*2and*3belong to loss of function CYP2C19alleles which decrease the inhibition of clopidogrel on platelet aggregation. The prevalence of the loss of function CYP2C19alleles in Asia was higher than that in Europe and America. There has been rare research for clopidogrel co-administered with PPIs on platelet aggregation in Chinese. So the first step of this research was to study the loss of function CYP2C19alleles in Chinese Han population. Then, the effects of clopidogrel on platelet aggregation was analysised in the CHD patients who were treated clopidogrel co-administered with PPIs and those patients who carried of loss of function CYP2C19alleles. Finally, the effects on early myocardial injury were determined in the elective PCI patients who received clopidogrel co-administered with different PPIs and those patients who carried of loss of function CYP2C19alleles. Three parts are showed as below.Part1The prevalence of the loss of function CYP2C19alleles in Chinese Han population.Objective:To investigate the prevalence of the loss of function CYP2C19alleles in Chinese Han population.Methods:1108consecutive volunteers were enrolled in this study, CYP2C19*2and*3genotype were performed by real-time PCR-TaqMan assay.Results:The prevalence of CYP2C19*1/*1、*1/*2、*2/*2、*1/*3、*2/*3、 *3/*3were39.53%、35.83%、8.48%、8.84%、6.32%and1%,respectively.Conclusions:The prevalence of loss of function CYP2C19alleles were about60%in Chinese Han population.Part2Effects of different PPIs on the antiplatelet activity of clopidogrel in CHD patientsObjective:To examine the effects of different PPIs on the antiplatelet activity of clopidogrel in CHD patients with or without loss of function CYP2C19alleles.Methods:A total of164CHD patients admitted to the hospital were divided into four groups by administion of different PPIs:Group Omeprazole (35patients, omeprazole20mg daily、Group Esomeprazole(50patients, esomeprazole40mg daily)、Group Pantoprazole (41patients, pantoprazole40mg daily) and Group without PPIs (38patients). All patients were administered with aspirin (100mg daily) and clopidogrel (300loading dose,75mg daily thereafter). Blood samples for examining platelet aggregation and genotype were obtained from all patients before administion of clopidogrel and three days after. ADP (10u1)-induced platelet aggregation was assessed by multiple electrode aggregometry. The inhibition rate of clopidogrel on platelet aggregation=platelet aggregation before clopidogrel admonition—platelet aggregation after clopidogrel admonition/platelet aggregation before clopidogrel administion×100%. CYP2C19*2and*3genotype were performed by real-time PCR-TaqMan assay.Results:The inhibition rate of clopidogrel on platelet aggregation in the Group Omeprazole, Group Esomeprazole, Group Pantoprazole and Group without PPIs were40.93%,41.24%,46.67%and47.59%respectively. The inhibition rate of clopidogrel on platelet aggregation had a descending trend in the Group Omeprazole, Group Esomeprazole, Group Pantoprazole and Group without PPIs, but there were no significant difference among the four groups (P>0.05). The inhibition rate of clopidogrel on platelet aggregation had significant difference in non-carriers group and carriers of loss of function CYP2C19alleles group in all patients (41.21%vs39.33%, P<0.05). The patients of four groups were divided into non-carriers groups and carriers of loss of function CYP2C19alleles groups furthermore. The inhibition rate of clopidogrel on platelet aggregation had no significant difference among these eight groups (P>0.05), and had no significant difference in non-carriers group and carriers of loss of function CYP2C19alleles group in different PPIs groups (P>0.05)Conclusions:The inhibition rate of clopidogrel on platelet aggregation was reduced in the CHD patients who carried of loss of function CYP2C19alleles. The inhibition rate of clopidogrel on platelet aggregation wasn’t affected by co-admonition with different PPIs in CHD patients, and wasn’t affected by co-admonition with different PPIs in CHD patients who carriered of loss of function CYP2C19alleles.Part3Influence of different PPIs combined with clopidogrel on early myocardial injury in elective PCI patientsObjective:To evaluate the influence of different PPIs combined with clopidogrel on early myocardial injury in elective PCI patients with or without loss of function CYP2C19alleles.Methods:A total of149patients with PCI were divided into four groups administered with different PPIs:Group Omeprazole (32patients, omeprazole20mg daily)、Group Esomeprazole (42patients, esomeprazole40mg daily)、 Group Pantoprazole (32patients, pantoprazole40mg daily) and Group without PPIs (43patients). All patients were administered with aspirin (100mg daily) and clopidogrel (300loading dose,75mg daily thereafter). Blood samples for examining cTnI and genotype were obtained from all patients on the next day after PCI。Positive cTnI was defined as cTnI>Ing/ml. CYP2C19*2and*3genotyping were performed by real-time PCR-TaqMan assay.Results:The positive rate of cTnI in Group Omeprazole, Group Esomeprazole, Group Pantoprazole and Group without PPIs were12.5%,11.9%,15.6%and9.3%respectively, and showed no significant difference in the four groups (P>0.05). The positive rate of cTnI in non-carriers groups and earriers of loss of function CYP2C19alleles groups in all patients were 12.07%and12.09%and showed no significant difference in the two groups (P>0.05). The patients of the four groups were divided into non-carriers groups and carriers of loss of function CYP2C19alleles groups furthermore. The positive rate of cTnl had no significant difference in these eight groups (P>0.05), and had no significant difference in non-carriers groups and carriers of loss of function CYP2C19alleles groups in different PPIs groups (P>0.05)Conclusions:There were no effects on early myocardial injury in the elective PCI patients co-administered with different PPIs and in the elective PCI patients who carried of loss of function CYP2C19alleles co-administered with different PPIs. Omeprazole. Esomeprazole or Pantoprazole can be selected in CHD patients co-administered with clopidogrel, but Pantoprazole may be the optimum.