Paraoxonase-1 activity affects the clopidogrel response in CYP2C19 loss-of-function carriers |
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Authors: | Ryo Nishio Toshiro ShinkeHiromasa Otake Masayuki NakagawaTakumi Inoue Hirotoshi HarikiTsuyoshi Osue Yu TaniguchiMasamichi Iwasaki Noritoshi HiranumaAkihide Konishi Hiroto KinutaniMasaru Kuroda Ken-ichi Hirata |
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Affiliation: | Kobe University Graduate School of Medicine, Division of Cardiovascular Medicine, Department of Internal Medicine |
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Abstract: | BackgroundThe impact of paraoxonase-1 (PON1) activity on the response to clopidogrel may differ in patients treated with drug-eluting stents (DES) in association with CYP2C19 loss-of-function (LOF) polymorphisms.MethodsThis study included 112 Japanese patients receiving clopidogrel (75 mg/day) and aspirin (100 mg/day) who underwent optical coherence tomography (OCT) examination 9 months after DES implantation. The CYP2C19 genotype was analyzed and LOF carriers (*1/*2, *1/*3, *2/*2, *3/*3, *2/*3) were identified. At the 9-month follow-up, platelet reactivity was determined by measuring the P2Y12 reactivity unit (PRU) using a VerifyNow P2Y12 assay, PON1 activity was evaluated and intra-stent thrombus was evaluated by OCT.ResultsOf the 112 Japanese patients, 75 were LOF carriers (67.0%). The patients were divided into tertiles according to the PON1 activity (tertile 1; < 230 U/L, tertile 2; 230–283 U/L, tertile 3; > 283 U/L). In the VerifyNowP2Y12 analysis, tertile 1 had a higher PRU than tertiles 2 and 3 in LOF carriers, and there was no difference among tertiles in non-carriers. The highest incidence of intra-stent thrombus was observed in tertile 1 followed by tertiles 2 and 3 in LOF carriers, whereas there was no such difference in non-carriers. Multivariate analysis revealed that LOF carriers and PON1 activity tertile 1 were independent predictors of intra-stent thrombus in all patients. In LOF carriers, tertile 1 was the only independent predictor for intra-stent thrombus.ConclusionLow PON1 activity is associated with a low response to clopidogrel and a high frequency of intra-stent thrombus only in LOF carriers. |
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Keywords: | PON1, paraoxonase-1 DES, drug-eluting stent CYP, cytochromeP450 LOF, loss-of-function OCT, optical coherence tomography PRU, platelet reactivity unit PCI, percutaneous coronary intervention SES, sirolimus-eluting stent PES, paclitaxel-eluting stent EES, everolimus-eluting stent TLR, target lesion revascularization MI, myocardial infarction |
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