Characterization of patients with angioscopically-detected in-stent mural thrombi – genetics of clopidogrel responsiveness and generations of drug-eluting stents.
BACKGROUND
The loss-of-function genotype of cytochrome P450 2C19 (CYP2C19) has been proposed as a risk factor for stent thrombosis in patients with drug-eluting stent implantation. The aim of this study was to clarify the clinical features of patients with angioscopically-detected in-stent mural thrombi (ISMT).


RESULTS
Enrolled were 100 stented segments in 55 patients with stable angina (20 bare-metal stents; 39 Cypher sirolimus-eluting stents [SES]; 26 Endeavor zotarolimus-eluting stents [ZES]; 13 Xience V everolimus-eluting stents; and 2 Nobori biolimus-eluting stents). Dual antiplatelet therapy (100 mg aspirin+75 mg clopidogrel once daily) had been continued since stenting. A poor metabolizer (PM) of clopidogrel was defined as a homozygote of CYP2C19 loss-of-function alleles. Coronary angioscopy revealed ISMT in 6 patients (5 SES, 1 ZES). Between the ISMT group and control group (n=49), there were no significant differences with regards to the VerifyNow P2Y12platelet function assay or in-stent endothelial coverage grade. Exact logistic regression analyses with stepwise forward selection at a significance level of 0.10 were performed to reveal predictive variables for ISMT (respectively: odds ratio, 95% confidence interval, P value: CYP2C19 PM genotype (3.28, 0.88-24.80, 0.09), SES implantation (3.37, 0.90-28.09, 0.08), and presence of yellow plaque (3.69, 1.14-25.70, 0.02).


CONCLUSIONS
Patients with ISMT were characterized by SES implantation, poor clopidogrel metabolism, and in-stent yellow plaque.
Department of Cardiology, Higashi-osaka City General Hospital.
Minoru
M
Ichikawa
Yoshizumi
Y
Takei
Toshimitsu
T
Hamasaki
Yoshiyuki
Y
Kijima
D065767:Activation, Metabolic / Q000235:genetics; D000368:Aged; D000483:Alleles; D000787:Angina Pectoris / Q000209:etiology; D017546:Angioscopy; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D017023:Coronary Angiography; D003328:Coronary Thrombosis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D065731:Cytochrome P-450 CYP2C19 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents / Q000145:classification; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D054328:Proton Pump Inhibitors / Q000494:pharmacology; D058925:Receptors, Purinergic P2Y12 / Q000032:analysis; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine; D001241:Aspirin