CYP2C19 Gene Detection Optimizes Dual Antiplatelet Treatment

BackgroundsThe rupture or canker of unstable coronary atherosclerosis plaque causing coronary artery thrombosis formation is considered to be the main pathological basis of Acute Coroary Syndrome(ACS). Platelet activation plays a very important role in the process of the disease, and therefore antiplatelet therapy in the treatment of ACS is critical. It can prevent myocardial infarction and improve prognosis. Aspirin and P2Y12 receptor antagonist are commonly used as antiplatelet drugs. The latter is divided into two categories according to the chemical structure. One is thienopyridine classes including clopidogrel and prasugrel and so on. The other is non-thienopyridine classes including Ticagrelor and Cangrelor etc. Clopidogrel and Ticagrelor are the most often used as antiplatelet drugs in clinical practice. Ticagrelor belongs to the nonprecursor drugs and does not need to metabolize, and it can function immediately after absorption free of the impact of CYP2C19. On the contrary, Clopidogrel needs two hepatic cytochrome oxidase metabolism and then transform into active products. In this process, CYP2C19 participates the metabolism. When patients carry one or more CYP2C19 function lack allele(including * 2 * 3 allele), the proportion of clopidogrel converted into effective metabolites is reduced, and then the platelet inhibition is decreased and the risk of cardiovascular events are increased. According to the results of CYP2C19 gene detection, the clopidogrel metabolism type can be divided into poor metabolizer, intermdiate metabolizer and extensive metabolizer. The first two metabolic types need to increase the dose of clopidogrel or change it into another antiplatelet agent. Accordingly, which kind of antiplatelet therapy benefits more in clinical? It has not yet reached a clear or unified conclusion.ObjectiveThis study was to explore how to select antiplatelet therapy for patients who were diagonsed with acute coronary syndrome and needed elective percutaneous conronary intervention. And the patients' CYP2C19 genotype was intermdiate metabolizer. There are two methods for them to choose. One is high maintenance dose of clopidogrel, and the other is switching to Ticagrelor. Then we compared two groups of baseline clinical data, related inspection check index, coronary angiography in vascular lesions and stenting, and observed two groups of patients' bleeding events, major adverse cardiac events, the occurrence of adverse drug reactions and changes of the platelet aggregation rate after 1 month.MethodsThere were 207 patients diagnosed with acute coronary syndrome who were hospitalized in cardiovascular department of the first affiliated hospital of zhengzhou university between September and December in 2014. They received percutaneous conronary intervention and their genotypes of CYP2C19 were tested. 42 cases out of patients were poor metabolizer, 94 cases were intermdiate metabolizer and then 71 cases were extensive metabolizer. Initial preoperative antiplatelet therapy was all clopidogrel(300 mg)plus aspirin(300 mg). These 94 cases were included in this study, among which 65 were male, 29 were female. Then the selected patients were randomly divided into clopidogrel added amount group and Ticagrelor group, 47 cases of each. Patients' clinical baseline data were compared. They were tested platelet aggregation rate. After one month' follow-up, some events were recorded such as major adverse cardiac events, bleeding events and dyspnea. By using the SPSS 17.0 statistical software version, measurement data were showed by using mean±standard deviation and compared with the paired t test, while count data were showed by using rate or percentage and compared with chi-square test. It is statistcally significant if the P value is less than 0.05.Results1.According to the result of CYP2C19 genetic testing, 207 cases with ACS undegoing elective PCI were divided into three types, which are poor metabolizer, intermdiate metabolizer, extensive metabolizer. And they respectively account for 20.3%, 45.4%, 34.3%.2.The fllow-up results are below: The major adverse cardiac events, bleeding events and the incidence of adverse reactions had no significant statistical differences between the two group(P > 0.05). 3.The Changes of platelet aggregation rate are below:(1) if Given loading dose of clopidogrel(300 mg) after 24 h, platelet aggregation rate(PA1) in both groups had no significant difference(P>0.05).(2) After one month' treatment, platelet aggregation rate(PA2) of Ticagrelor group was significantly lower than that of clopidogrel added amount group(P<0.001).(3) Changes of platelet aggregation during one month(delta PA = PA1- PA2) were statistically significant(P = 0.001).ConclusionsFor patients who are intermdiate metabolizer, Ticagrelor has stronger platelet inhibition than high-dose clopidogrel, while the short-term clinical outcomes have no difference.