Effect of cytochrome P450 2C19*17 allelic variant on cardiovascular and cerebrovascular outcomes in clopidogrel?treated patients: A systematic review and meta?analysis

Abstract

Background: We aimed to evaluate the associations of gain?of?function  allele of CYP2C19*17 and risk of clinical events in clopidogrel?treated  patients with cardiovascular and cerebrovascular diseases (CCVDs).  Materials and Methods: Literature search was conducted in PubMed,  EMBASE, and Cochrane Library. Odds ratio (OR) combined with 95%  confidence interval (CI) was the pooled statistics. Subgroup analysis was performed by disease type, bleeding events, and race. Results: Thirteen eligible studies involving 14,239 patients with CYP2C19*17 carriers or noncarriers were included in the meta?analysis. CYP2C19*17 was significantly related to decreased risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with coronary artery disease (CAD) (OR = 0.76, 95% CI: 0.60–0.98, P = 0.03), however, irrelevant with stent thrombosis in neither CAD nor ischemic heart disease patients. CYP2C19*17 was also significantly linked to decreased risk of high platelet reactivity (HPR) inCCVD patients (OR = 0.61, 95% CI: 0.43–0.88, P = 0.008). Meanwhile, CYP2C19*17 was significantly associated with bleeding risk in CCVD patients (OR = 1.89, 95% CI: 1.09–3.25, P = 0.02) but not related to major bleeding risk (OR = 1.35, 95% CI: 0.87–2.08, P = 0.18). Several outcomes in Caucasian subgroup were reverse to the overall  results, such as bleeding events and HPR, which lacked significance.  Conclusion: CYP2C19*17 had a significant effect on the reduced risks of  MACCE and HPR as well as increased bleeding risk, but not on the risks of stent thrombosis and major bleeding in clopidogrel?treated CCVD patients. Outcomes might be different in different races