title: Adjunctive cilostazol versus high maintenance dose of clopidogrel in patients with hyporesponsiveness to chronic clopidogrel therapy.
abstract: OBJECTIVE
  Whether addition of cilostazol is superior to increasing dose of clopidogrel in patients with hyporesponsiveness to chronic clopidogrel therapy is unknown.
  
  
  METHODS
  We studied 73 patients with hyporesponsiveness to clopidogrel on standard dual antiplatelet therapy for more than 2 weeks. Clopidogrel hyporesponsiveness was defined as percent inhibition of P2Y12 reaction units (PRU) <30% on VerifyNow P2Y12 assay. Patients were randomly assigned to increased dose of clopidogrel (aspirin 100 mg+clopidogrel 150 mg daily: group A, n=38) or to receiving additional cilostazol (aspirin 100 mg+clopidogrel 75 mg+cilostazol 100 mg bid daily: group B, n=35).
  
  
  RESULTS
  Baseline percent inhibition of PRU and PRU was similar between 2 groups (13.0 ± 10.2% versus 11.8 ± 9.7%, p = 0.61, and 286.3 ± 54.7 versus 295.7 ± 53.7, p=0.44, respectively). At follow-up, percent inhibition of PRU was higher and PRU was lower significantly in group B than in group A (38.5 ± 17.9% versus 28.3 ± 16.6%, p=0.02, and 207.3 ± 68.2 versus 241.3 ± 76.7, p=0.050, respectively). Among those still showing hyporesponsiveness to clopidogrel at follow-up (21 patients in group A, 10 patients in group B), 12 patients completed further crossover study. Compared to the baseline, magnitude of change in percent inhibition of PRU and PRU showed an improved tendency after the crossover (from 2.7 ± 8.7% to 15.8 ± 18.4%, p=0.08, and from -18.6 ± 58.0 to -61.9 ± 84.3, p=0.08).
  
  
  CONCLUSIONS
  Adjunctive cilostazol improved clopidogrel responsiveness better than the higher maintenance dose of clopidogrel in hyporesponsive patients with chronic clopidogrel therapy.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Korea.
authors.forename: Ga Yeon
authors.initials: GY
authors.lastname: Lee
authors.forename: Joo-Yong
authors.initials: JY
authors.lastname: Hahn
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jun Hyung
authors.initials: JH
authors.lastname: Kim
authors.forename: Sang-Yup
authors.initials: SY
authors.lastname: Lee
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Song
authors.forename: Seung-Hyuk
authors.initials: SH
authors.lastname: Choi
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Hyeon-Cheol
authors.initials: HC
authors.lastname: Gwon
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects; D000077407:Cilostazol; D000077144:Clopidogrel; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011446:Prospective Studies; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism; D013777:Tetrazoles / Q000008:administration & dosage*; D013927:Thrombosis / Q000188:drug therapy; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D013777:Tetrazoles; D000077144:Clopidogrel; D000077407:Cilostazol; D013988:Ticlopidine