title: Pharmacodynamic effects of cilostazol versus clopidogrel in stented patients under proton pump inhibitor co-administration: the ACCEL-PARAZOL study.
abstract: OBJECTIVE
  Proton pump inhibitor (PPI) therapy has been shown to attenuate the antiplatelet effects of clopidogrel. The aim of this study was to compare the antiplatelet effects of cilostazol versus clopidogrel in patients co-administered a PPI.
  
  
  METHODS
  We enrolled PPI-naïve stented patients treated with standard clopidogrel and aspirin therapy for at least six months (n=100). The patients were randomly assigned to receive either cilostazol at a dose of 100mg twice daily (CILO group) or clopidogrel at a dose of 75mg daily (CLPD group) in addition to lansoprazole (30mg daily). The platelet aggregation (PA) determined using light transmittance aggregometry and the platelet reactivity index (PRI) obtained using a vasodilator-stimulated phosphoprotein phosphorylation assay were measured before randomization and at the 14-day follow-up visit. The primary endpoint was the PRI value at follow-up.
  
  
  RESULTS
  At follow-up, the CLPD group showed similar values of PRI as the CILO group (66.9±14.0% vs. 63.1±14.1%; mean difference: 3.9%; 95% confidence interval of difference: -1.7% to 9.4%; p=0.174). However, the 6μg/mL collagen- and 0.5mg/mL arachidonic acid-induced PA values in the CLPD group were higher than those observed in the CILO group (mean differences: 9.8% to 11.1%; all p values ＜0.001). CYP2C19 loss-of-function allele carriage was the major contributing factor associated with the PRI level in the absence of lansoprazole treatment (with a gene-dose effect); this association was not observed in the subjects receiving lansoprazole co-administration in the CLPD group.
  
  
  CONCLUSIONS
  During lansoprazole co-administration, cilostazol treatment achieves a more favorable platelet function profile than clopidogrel therapy. The use of combination treatment with cilostazol and aspirin deserves further attention with respect to the management of stable stented patients requiring PPI co-administration.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine.
authors.forename: Yongwhi
authors.initials: Y
authors.lastname: Park
authors.forename: Jin Mu
authors.initials: JM
authors.lastname: Jung
authors.forename: Udaya S
authors.initials: US
authors.lastname: Tantry
authors.forename: Kyehwan
authors.initials: K
authors.lastname: Kim
authors.forename: Jin Sin
authors.initials: JS
authors.lastname: Koh
authors.forename: Jeong Rang
authors.initials: JR
authors.lastname: Park
authors.forename: Seok-Jae
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Choong Hwan
authors.initials: CH
authors.lastname: Kwak
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Hwang
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Kim
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Jeong
mesh_terms: D002318:Cardiovascular Diseases / Q000188:drug therapy*; D000077407:Cilostazol; D000077144:Clopidogrel; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D064747:Lansoprazole / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010979:Platelet Function Tests; D011379:Prognosis; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy*; D015607:Stents; D013777:Tetrazoles / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D013777:Tetrazoles; D064747:Lansoprazole; D000077144:Clopidogrel; D000077407:Cilostazol; D013988:Ticlopidine