The gain‐of‐function variant allele CYP2C19*17: a double‐edged sword between thrombosis and bleeding in clopidogrel‐treated patients

Summary

Background: A large number of clinical studies have documented that a loss‐of‐function variant CYP2C19*2 affects clinical profiles of clopidogrel (efficacy and safety). However, data on the impact of a gain‐of‐function variant CYP2C19*17 on the response to that drug seem to be less consistent. Objectives: To systematically summarize all available clinical data assessing the role of the CYP2C19*17 variant in patients taking clopidogrel. Methods: A literature search was conducted and a meta‐analysis was performed for 11 eligible studies. The endpoints included the major adverse cardiovascular events (MACE, representing non‐fatal myocardial infarction, stroke, revascularization, or death), bleeding events, mortality, stent thrombosis and high platelet reactivity (HPR). Results: Data from six clinical studies demonstrated that carriers of the CYP2C19*17 variant had a marked protection against recurrent cardiovascular events in patients with coronary artery disease compared with non‐carriers, as measured by a 16% decrease in the incidence of MACE (10.0% vs. 11.9%; OR, 0.82; 95% CI, 0.72–0.94; P= 0.005). On the other hand, carriers had an increased risk of developing bleeding as expected (8.0% vs. 6.5%; OR, 1.25; 95% CI, 1.07–1.47; P= 0.006; four studies). Moreover, the presence of the CYP2C19*17 variant might lead to increased response to clopidogrel, as shown by a marked lower prevalence of HPR in carriers than in non‐carriers (37.9% vs. 50.8%; OR, 0.60; 95% CI, 0.45–0.79; P= 0.0003; three studies). Conclusions: Carriers of the CYP2C19*17 variant have greater therapeutic responsiveness to clopidogrel than non‐carriers, but they have an increased risk of developing bleeding as well.