Choong-Hwan Kwak

The CYP2C19*2 and CYP2C19*3 polymorphisms are associated with high post‐treatment platelet reactivity in Asian patients with acute coronary syndrome

Table S1. Data summary for coronary artery disease (CAD) patients including lipid profile, juxtaposed with the individual plasma total tissue factor potential (tTFp) values (expressed as percentage of normal plasma pool), and ACTI-FXa values (pmol L). Underlined/italics: patients presenting with diabetes. Fig. S1. Characterization immunoblot, using high-affinity tissue factor (TF) capture antibody SATF-IG 160. Left panel: detection of recombinant human TF forms. Right panel: detection of TF forms in human monocytic cells (THP-1); numbers on top indicate the amounts of cell lysate. Multiple bands of distinct apparent molecular weight, present between the major bands corresponding to full length TF (flTF) and alternatively spliced TF (asTF), most likely reflect variable glycosylation and/or propeptide processing of the two TF forms. Fig. S2. Compartmentalization of human plasma (normal plasma pool), following ultracentrifugation. The microparticle pellet is clearly visible at the bottom of the tube, spreading to the wall. Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article.

Influence of CYP2C19*2 and *3 loss-of-function alleles on the pharmacodynamic effects of standard- and high-dose clopidogrel in East Asians undergoing percutaneous coronary intervention: the results of the ACCEL-DOUBLE-2N3 study.

Y . -H . J EONG,*† 1 K . A . ABADILLA ,†‡ 1 U . S . TANTRY ,† Y . PARK ,* J . S . KOH,* C . H . KWAK,* J . -Y . HWANG* and P . A . GURBEL† *Department of Internal Medicine, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine, Jinju, Korea; †Sinai Center for Thrombosis Research; and ‡Department of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD, USA

Pharmacodynamic effect of clopidogrel therapy and switching to cilostazol in patients with the CYP2C19 loss-of-function allele (ACCEL-SWITCH) study.

Restenosis and stent thrombosis (ST) are catastrophic events that can occur in stented patients. In spite of the development of the drug-eluting stent (DES) platform, selected DES-treated patients still suffer from these clinical events [1]. Early events (within post-stent 30 days) are more likely as a result of mechanical issues, inadequate platelet inhibition or the prothrombotic profile, whereas late events may be attributed to biological issues such as delayed re-endothelialization, inflammation, and impaired vascular function and remodeling [2]. In addition to use of new generation DES, optimal pharmacologic regimens may reduce DES-related complications [2]. Adjunctive medications such as statin and thiazolidinedione may reduce the risk of restenosis through stem cell homing balancing the re-endothelialization and neointimal proliferation, whereas antiplatelet therapy may decrease the risk of DES-mediated ST. Cilostazol is a reversible dual inhibitor of adenosine uptake and phosphodiesterase 3 (PDE3) [3]. In addition to its antiplatelet effect, cilostazol has pleotropic effects influencing stem cell homing, re-endothelialization, vascular repair and inflammation process [3,4]. In DES-treated patients, compared with aspirin and clopidogrel treatment, adjunctive cilostazol therapy not only decreased the risk of restenosis by 40% [5] but also reduced the prevalence of 1year ST (hazard ratio, 0.14; P = 0.004) without increasing the risk of bleeding [6]. Furthermore, treatment with cilostazol and aspirin in diabetic patients showed similar efficacy in decreasing post-DES ischemic events and lessened the risk of restenosis compared with treatment with clopidogrel and aspirin [7]. About two-third of East Asians have the CYP2C19 lossof-function (LoF) allele, which is associated with increased on-treatment platelet aggregation (PA) during clopidogrel treatment [8], but the rate of ischemic events appeared to be similar to Caucasians [8,9]. Because East Asians may have a different thrombogenic property and platelet reactivity threshold for adverse event occurrences, the concept of tailored antiplatelet therapy balancing clinical efficacy and safety is more important during the post-percutaneous coronary intervention (PCI) late phase. Cilostazol therapy with its low bleeding risk and pleiotropic effects [3] may be another alternative option for this population, but a previous report showing the lower pharmacodynamic effect of cilostazol compared with clopidogrel [10] may be a limitation of its clinical application. However, the pharmacodynamic effects of clopidogrel and cilostazol are significantly related to the CYP2C19 LoF variant [3,8]. We thus performed the present study to compare the effect of clopidogrel and switching to cilostazol in DES-treated patients with the CYP2C19 LoF allele. Between January 2010 and December 2010, in this prospective, observational study, 20 CYP2C19*1 homozygotes and 27 carriers of the CYP2C19 LoF allele receiving clopidogrel (75 mg daily) and aspirin for at least 6 months after DES implantation (Fig. 1A) were recruited. In CYP2C19 LoF allele carriers, clopidogrel was switched to cilostazol (100 mg twice daily). CYP2C19*1 homozygotes were used as the control group to evaluate variability in clopidogrel responsiveness over time. At 14 ± 3 days follow-up, compliance and adverse events were assessed based on interview, pill counting, a questionnaire and laboratory evaluation. Blood sampling was conducted at 2–6 h after the last-dose ingestion, and the data were enrolled for the analysis if patients showed 100% compliance. Genotyping and the platelet function assay (conventional aggregometry and the VerifyNow P2Y12 assay Correspondence: Young-Hoon Jeong, Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, 90 Chiram-dong, Jinju, Gyeongsangnam-do 660-702, South Korea. Tel.: +8 255 750 8873; fax: +8 255 758 9122. E-mail: goodoctor@naver.com

Isolated Left Main Coronary Artery Spasm Detected by Multidetector Computed Tomography

Although atherosclerotic obstruction is the main cause of left main coronary artery (LMCA) disease, it can also be associated with vasospasm. We report a case of a 61-year-old male who presented with ostial stenosis of the LMCA, detected by 64-slice multi-detector computed tomographic coronary angiography (MDCT-CA). Careful review of MDCT and intravascular ultrasound findings showed suspicion of an isolated spasm of the LMCA without a significant atherosclerotic lesion. The patient was successfully treated with nitrates and a calcium channel blocker.