A case of subacute thrombosis associated with clopidogrel resistance after implantation of a zotarolimus-eluting stent.
ABSTRACT A 73-year-old woman was admitted to our hospital with anterior acute myocardial infarction due to subacute thrombosis after coronary stenting with a zotarolimus-eluting stent (ZES), which is a newly developed drug-eluting stent that has been widely used since May 2009 in Japan. Five days before, she underwent implantation with a ZES in the left anterior descending artery due to stable angina pectoris. After stenting, the intravascular ultrasonography showed no malapposition from the proximal to the distal edge of the stent. She received aspirin 100 mg/day and clopidogrel 75 mg/day from 2 weeks before the stent was implanted. When we investigated the single nucleotide polymorphisms of CYP2C19 in this patient, both CYP2C19*2 and CYP2C19*3 were detected, and she was classified as a poor metabolizer. This report is the first to describe subacute stent thrombosis following the implantation of a newly developed ZES in a Japanese patient, which may be related to clopidogrel resistance.
- SourceAvailable from: Catherine Goyenvalle[show abstract] [hide abstract]
ABSTRACT: The capacity of clopidogrel to inhibit ADP-induced platelet aggregation shows wide intersubject variability. To determine whether frequent functional variants of genes coding for candidate cytochrome P450 (CYP) isoenzymes involved in clopidogrel metabolic activation (CYP2C19*2, CYP2B6*5, CYP1A2*1F, and CYP3A5*3 variants) influence the platelet responsiveness to clopidogrel, we conducted a prospective pharmacogenetic study in 28 healthy white male volunteers treated for 7 days with clopidogrel 75 mg/d. We observed that pharmacodynamic response to clopidogrel was significantly associated with the CYP2C19 genotype. Twenty of the subjects were wild-type CYP2C19 (*1/*1) homozygotes, while the other 8 subjects were heterozygous for the loss-of-function polymorphism CYP2C19*2 (*1/*2). Baseline platelet activity was not influenced by the CYP2C19 genotype. In contrast, platelet aggregation in the presence of 10 muM ADP decreased gradually during treatment with clopidogrel 75 mg once daily in *1/*1 subjects, reaching 48.9% +/- 14.9% on day 7 (P < .001 vs baseline), whereas it did not change in *1/*2 subjects (71.8% +/- 14.6% on day 7, P = .22 vs baseline, and P < .003 vs *1/*1 subjects). Similar results were found with VASP phosphorylation. The CYP2C19*2 loss-of-function allele is associated with a marked decrease in platelet responsiveness to clopidogrel in young healthy male volunteers and may therefore be an important genetic contributor to clopidogrel resistance in the clinical setting.Blood 10/2006; 108(7):2244-7. · 9.06 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The clinical and angiographic predictors of early (<30 days) stent thrombosis (ST) have not been reported in high-risk patients with acute coronary syndromes. Qualitative and quantitative coronary angiographic analyses were performed in 3405 patients with moderate- and high-risk acute coronary syndromes in whom stents were implanted in the prospective randomized Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial, including 3043 patients (89.4%) in whom drug-eluting stents were implanted. Within 30 days, definite or probable ST occurred in 48 patients (1.4%). ST rates were not significantly different in patients treated with bare metal stents compared with drug-eluting stents (1.4% versus 1.4%; P=1.00) or with heparin plus glycoprotein IIb/IIIa inhibitors (1.1%) compared with bivalirudin with or without IIb/IIIa inhibitors (1.6% and 1.5%, respectively; P=0.26 and P=0.37, respectively). Compared with patients without ST, patients with ST more frequently had insulin-requiring diabetes mellitus and baseline renal insufficiency, a greater overall burden of coronary atherosclerosis, and suboptimal final angiographic results. ST also was more common in patients without preprocedural thienopyridine administration and with inconsistent antiplatelet drug use within 30 days. By multivariable analysis, the strongest independent predictors of definite ST were a smaller final stent minimal lumen diameter, a lack of preprocedural thienopyridine administration, the extent of coronary artery disease, and higher baseline hemoglobin level. Occurring in nearly 1 in 70 patients, early ST is relatively common in acute coronary syndromes, occurs with similar frequency after anticoagulation with either heparin plus glycoprotein IIb/IIIa inhibitors or bivalirudin with or without IIb/IIIa inhibitors, and is predicted by diffuse atherosclerosis, suboptimal angiographic results, and inadequate pharmacotherapy.Circulation 02/2009; 119(5):687-98. · 15.20 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Recurrence of myocardial infarction, especially when occurring early after the prior one, carries a significant morbidity and mortality rate. The aim of this study was to investigate the characteristics of patients who experienced recurrence under secondary prevention therapy. Case record review identified myocardial infarction patients who had a history of previous myocardial infarction within 5 years. Hospital chart records, initial laboratory data, medications, and type of infarction were reviewed. Patients were divided into two groups according to the interval of recurrence: an early group (recurrence within 1 year), and a late group (recurrence after more than 1 year). A total of 89 patients were included in the analysis; 40 patients in the early group, and 49 patients in the late group. Mean age in the early group and late groups was 67.3 +/- 11.9 and 59.4 +/- 8.9, respectively (P = 0.001). Mean body mass index in the early and late groups was 22.1 +/- 3.6 and 25.0 +/- 3.3, respectively (P < 0.001). There were fewer current smokers in the early group (7.5% vs 44.9%, P < 0.001) and more stent thrombosis (17.5% vs 2%, P = 0.02), as compared with the late group. The in-hospital mortality rate tended to be higher in the early group (7.5% vs 0%, P = 0.09). Multiple logistic regression revealed that smoking status (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.02-0.49, P = 0.005), HDL cholesterol level (5 mg/dl increase: OR 1.34, 95% CI 1.04-1.74, P = 0.03), and stent thrombosis (OR 35.59, 95% CI 2.13-595.49, P = 0.01) had significant associations with early recurrence. Early recurrence of myocardial infarction was associated with stent thrombosis, a higher HDL cholesterol level, and a lower frequency of smoking. Early recurrence had a trend toward higher mortality than late recurrence.Heart and Vessels 09/2009; 24(5):347-51. · 2.13 Impact Factor