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

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) in CCVD 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.