Background: The 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.
Methods: This study included 112 Japanese patients receiving clopidogrel (75 mg/day) and aspirin (100mg/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.
Results: Of 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; 230-283U/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.
Conclusion: Low PON1 activity is associated with a low response to clopidogrel and a high frequency of intra-stent thrombus only in LOF carriers.
Keywords: CYP; CYP2C19; DES; EES; LOF; MI; OCT; PCI; PES; PON1; PRU; Paraoxonase-1; SES; TLR; VerifyNowP2Y12; clopidogrel; cytochromeP450; drug-eluting stent; everolimus-eluting stent; intra-stent thrombus; loss-of-function; myocardial infarction; optical coherence tomography; paclitaxel-eluting stent; paraoxonase-1; percutaneous coronary intervention; platelet reactivity unit; sirolimus-eluting stent; target lesion revascularization.
© 2013.