The comparison of the additional effect between high dose clopidogrel and cilostazol in clopidogrel low responder after drug-eluting stent implantation

Abstract

Low response to standard clopidogrel therapy (75mg/day) assessed by a ponit-of-care assay has been associated with thrombotic events after drug-elution stent (DES) implantation. We hypothesized that high dose clopidogrel (150mg/day) or adding cilostazol (200mg/day) on standard clopidogrel could improve the clopidogrel low responder in patients with drug eluting stent implantations. We selected consecutive 63 patients with clopidogrel low responder defined as a inhibition of platelet aggregation (IPA, percentage inhibition of P2Y12 receptor) less than 20% assessed by VeryfyNow P2Y12 assay (Accumetrics, San Diego, CA). We randomly allocated three groups: standard maintenance dose (SMD) clopidogrel group (75mg/day of clopidogrel, 20 patients), high maintenance dose (HMD) clopidogrel group (150mg/day of clopidogrel, 22 patients) and adding cilostazol (AC) group (adding 200mg/day of cilostazol, 21 patients). After 2 weeks of treatments, we reevaluated PRU value and a inhibition of platelet aggregation (IPA, %inhibition of P2Y12 receptor). Baseline demographies were similar among three groups. Baseline P2Y12 Reaction Unit (PRU) value was 285.1±58.2, 270.9±50.0 and 287.8±56.9 in SMD group, HMD group and AC group (p=0.598) and the baseline inhibition of platelet aggregation (IPA) was 9.2±7.8, 9.0±6.7 and 9.6±7.0 in SMD group, HMD group and AC group (p=0.969). Post-treatment P2Y12 Reaction Unit (PRU) value was 270.7±60.3, 231.4±92.1 and 207.3±51.3 in SMD group, HMD group and AC group (p=0.065). The post-treatment inhibition of platelet aggregation(IPA) was 14.5±8.9, 21.4±16.9 and 31.3±19.2 in SMD group, HMD group and AC group (p=0.006). After 14 days of treatment, the proportion of clopidogrel low responder defined less than IPA 20% was 80%, 54.5% and 33.3% in SMD group, HMD group and AC group (p=0.008).

Our results clearly showed adding cilostazol to standard dosage of clopidogrel is effectively inhibited the platelet assessed by VerifyNow P2Y12 compare to the standard or high dose of clopidogrel in patients with clopidogrel resistance.