Effect of high-dose clopidogrel according to CYP2C19*2 genotype in patients undergoing percutaneous coronary intervention- a systematic review and meta-analysis.

High-dose clopidogrel has been recommended to overcome clopidogrel non-responsiveness in patients undergoing percutaneous coronary intervention (PCI), especially those with CYP2C19 loss-of-function genotypes. However, there is controversy over the pharmacodynamics and clinical effects of the strategy. This meta-analysis was conducted to evaluate the antiplatelet effects of high-dose clopidogrel according to CYP2C19*2 alleles in patients undergoing PCI. Methods Based on PubMed, Cochrane, and EMBASE prior to June 1st, 2014, a systematic review and meta-analysis was conducted to evaluate the antiplatelet effects of high-dose clopidogrel on platelet reactivity and clinical outcomes in PCI treated patients according to CYP2C19*2 genotypes. The reported outcomes including on-treatment platelet reactivity (OTPR), high on-treatment platelet reactivity (HTPR), major adverse cardiovascular events (MACE), stent thrombosis and composite cardiovascular events. Results Nineteen studies involving 10,960 patients were included. After high-dose clopidogrel administration (600/900mg loading dose and/or 150mg/day maintenance dose), compared with non-carriers, carriers of CYP2C19*2 genotype had significantly increased OTPR (SMD for VASP assay: 0.69, 95% CI: 0.48-0.90, p=4×10-4; for VerifyNow P2Y12 assay: 0.70, 95% CI: 0.54-0.85, p<10-5; for LTA assay:0.58, 95% CI: 0.48-0.69, p=4×10-4). The incidence rate of HTPR was higher in CYP2C19*2 carriers after high-dose clopidogrel treatment (RR: 1.21, 95% CI:1.05-1.39, p=0.008 for cutoff PRI >50% by VASP assay; RR: 1.69, 95% CI: 1.44-1.98, p<1×10-4 for cutoff PRU >230 by VerifyNow P2Y12 assay). As for clinical outcomes, CYP2C19*2 was associated with higher risk for MACE (RR: 1.68, 95% CI: 1.19- 2.37, p=0.003), stent thrombosis (RR: 1.75, 95% CI: 1.31-2.34, p=0.0001), as well as composite cardiovascular events (RR: 1.82, 95% CI: 1.42- 2.34, p<10-5) after treated by high-dose clopidogrel. Conclusion High-dose clopidogrel could not overcome the variability of clopidogrel antiplatelet effects between the CYP2C19 *2 carriers and non-carriers in patients treated with PCI. [ABSTRACT FROM AUTHOR]