Randomized Comparison of Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With High Post-Treatment Platelet Reactivity : Results of the ACCEL-RESISTANCE (Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients

ObjectivesThe purpose of this study was to determine the impact of adjunctive cilostazol in patients with high post-treatment platelet reactivity (HPPR) undergoing coronary stenting.BackgroundAlthough addition of cilostazol to dual antiplatelet therapy enhances adenosine diphosphate (ADP)-induced platelet inhibition, it is unknown whether adjunctive cilostazol can reduce HPPR.MethodsSixty patients with HPPR after a 300-mg loading dose of clopidogrel were enrolled. HPPR was defined as maximal platelet aggregation (Aggmax) >50% with 5 μmol/l ADP. Patients were randomly assigned to receive either adjunctive cilostazol (triple group; n = 30) or high maintenance dose (MD) clopidogrel (high-MD group; n = 30). Platelet function was assessed at baseline and after 30 days with conventional aggregometry and the VerifyNow assay.ResultsBaseline platelet function measurements were similar in both groups. After 30 days, significantly fewer patients in the triple versus high-MD group had HPPR (3.3% vs. 26.7%, p = 0.012). Percent inhibitions of 5 μmol/l ADP-induced Aggmaxand late platelet aggregation (Agglate) were significantly greater in the triple versus high-MD group (51.1 ± 22.5% vs. 28.0 ± 18.5%, p < 0.001, and 70.9 ± 27.3% vs. 45.3 ± 23.4%, p < 0.001, respectively). Percent inhibitions of 20 μmol/l ADP-induced Aggmaxand Agglatewere consistently greater in the triple versus high-MD group. Percent change of P2Y12 reaction units demonstrated a higher antiplatelet effect in the triple versus high-MD group (39.6 ± 24.1% vs. 23.1 ± 29.9%, p = 0.022).ConclusionsAdjunctive cilostazol reduces the rate of HPPR and intensifies platelet inhibition as compared with a high-MD clopidogrel of 150 mg/day.