CYP2C19 loss-of-function (LOF) alleles adversely affect clinical outcome of
clopidogrel therapy. Recent introduction of a newer-generation
drug-eluting stent (DES) has significantly reduced the occurrence of
stent thrombosis.The aim of this study was to evaluate the impact of
CYP2C19 LOF alleles on clinical outcome in patients treated with the newer-generation DES.The effects of
CYP2C19 genotypes were evaluated on clinical outcome of
clopidogrel therapy in 2062 patients treated with
percutaneous coronary intervention using either first-generation DES (
sirolimus- and
paclitaxel-eluting
stent, n = 1349) or newer-generation DES (
everolimus- and
zotarolimus-eluting
stent, n = 713). The primary clinical outcome was major cardiac and cerebrovascular event (MACCE) including
cardiac death, nonfatal
myocardial infarction,
stroke, and
stent thrombosis during 1 year of follow-up.CYP2C19 LOF alleles were significantly associated with a higher risk of MACCE in patients treated with first-generation DES (hazard ratio [HR] 2.599, 95% confidence interval [CI] 1.047-6.453; P = 0.034). In contrast,
CYP2C19 LOF alleles were not associated with primary outcome in newer-generation DES (HR 0.716, 95% CI 0.316-1.622; P = 0.522). In the further multivariate analysis,
CYP2C19 LOF alleles were not associated with MACCE in patients receiving newer-generation DES (adjusted HR 0.540, 95% CI 0.226-1.291; P = 0.166), whereas they were demonstrated to be an independent risk factor for MACCE in those implanted with first-generation DES (adjusted HR 3.501, 95% CI 1.194-10.262; P = 0.022).In contradiction to their clinical impact in first-generation DES era,
CYP2C19 LOF alleles may not affect clinical outcome of
clopidogrel therapy in patients treated with newer-generation DES.