ABSTRACT
OBJECTIVE： To evaluate efficacy and safety of individualized antiplatelet therapy in patients with coronary artery disease （CAD） systematically according to the results of laboratory examination， and to provide reference for individualized antiplatelet therapy in clinic. METHODS： Retrieved from PubMed， Embase and the Cochrane library during the establishment of database to Feb. 2018， RCTs about individualized antiplatelet therapy vs. routine antiplatelet therapy in CAD patients based on the results of laboratory examination were collected. Meta-analysis was conducted for the incidence of main adverse cardiovascular adverse events （MACE）， all-cause death， cardiovascular death， myocardial infarction， stent thrombosis， stroke and severe bleeding by using Rev Man 5.3 statistical software after data extraction and quality evaluation with Cochrane system evaluator manual 5.2.0. Subgroup analysis was carried out for different races， laboratory testing methods and intervention courses. RESULTS： Totally 7 RCTs involving 8 615 patients were included. Results of Meta-analysis showed that compared with routine antiplatelet therapy， there was no significant difference in the incidence of MACE [RR＝0.93， 95％CI （0.74， 1.16）， P＝0.51]， all-cause death [RR＝0.89， 95％CI （0.56， 1.41）， P＝0.61]， cardiovascular death [RR＝0.68， 95％CI （0.36， 1.25）， P＝0.21]， myocardial infarction [RR＝1.03， 95％CI （0.92， 1.16）， P＝0.56]， stent thrombosis [RR＝0.52， 95％CI （0.22， 1.24）， P＝0.14]， stroke [RR＝1.03， 95％CI （0.65， 1.63）， P＝0.90]， and severe bleeding [RR=0.78，95％CI （0.53， 1.14）， P＝0.20] based on the results of laboratory examination. Subgroup analysis showed according to CYP2C19 genotype， individualized medication could reduce the incidence of MACE [RR＝0.29， 95％CI （0.14， 0.64）， P＝0.002] and all-cause death [RR＝0.11， 95％CI （0.01， 0.87）， P＝0.04]， and trials with intervention duration of 6 months could significantly decrease the incidence of all-cause death [RR＝0.11， 95％CI （0.01， 0.87）， P＝0.04]， there were no significant difference between 2 groups in other subgroup analysis. CONCLUSIONS： Compared with routine antiplatelet therapy， individualized antiplatelet therapy based on the results of laboratory examination cannot reduce the incidence of MACE and bleeding event risk in real-world patients with CAD. Although subgroup analysis show that individualized medication on the basis of CYP2C19 genotype can significantly reduce the incidence of MACE and cardiovascular death. But more large-scale samples and high-quality studies are needed to confirm this conclusion.
ABSTRACT
This study established a population pharmacokinetics-pharmacodynamics model of clopidogrel in patients with acute coronary syndrome. Fifty-nine patients were enrolled. The plasma concentration of clopidogrel active metabolite and vasodilator stimulated phosphoprotein platelet reactivity index (VASP-PRI) were selected as the pharmacokinetics index and the pharmacodynamics index, respectively. The covariates including demographic characteristics, laboratory indexes, combined medication, complications and genetic polymorphisms of related enzymes were screened for their influence on the pharmacokinetic and pharmacodynamics parameters. Population pharmacokinetic and pharmacodynamics data analysis was performed using NONMEM software. The general linear model and the indirectly effect model-turnover model for pharmacokinetic and pharmacodynamic analysis were selected as the basic model, respectively. The population typical values of K12, CL/F, V/F, EC50, K(in), and E(max) were 0.259 h(-1), 179 L x h(-1), 632 L, 1.57 ng x mL(-1), 4.29 and 0.664, respectively. CYP2C19 was the covariate in the final pharmacokinetic model, and the model was to design a prior dosage regimen.