Pharmacodynamic Effects of Cilostazol Versus Clopidogrel in Stented Patients under Proton Pump Inhibitor Co-administration: The ACCEL-PARAZOL Study

Abstract

Aim: 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-naive 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 100 mg twice daily (CILO group) or clopidogrel at a dose of 75 mg daily (CLPD group) in addition to lansoprazole (30 mg 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 6 mu g/mL collagen-and 0.5 mg/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.