title: Dual antiplatelet therapy clopidogrel with low-dose cilostazol intensifies platelet inhibition in patients with ischemic stroke.
abstract: OBJECTIVE
  We previously reported that the antiplatelet action is intensified with combined use of clopidogrel and cilostazol in ischemic stroke patients using the VerifyNow P2Y12 Assay. In this study, the relationship between the cilostazol dose and the platelet function achieved with combination therapy was investigated.
  
  
  METHODS
  The subjects included 231 patients with noncardiogenic ischemic stroke treated at our hospital (18 patients treated with a combination of clopidogrel (75 mg) and cilostazol (100 mg), 52 patients treated with a combination of clopidogrel (75 mg) and cilostazol (200 mg), 126 patients treated with clopidogrel (75 mg) alone and 35 patients treated with cilostazol (200 mg) alone). The platelet function achieved with 20 μM of adenosine diphosphate was measured using the VerifyNow P2Y12 Assay. Clopidogrel resistance was defined as P2Y12 Reaction Units (PRU) >230 and/or % inhibition <20%. Results The PRU was >230 in 32 patients (25.4%) receiving clopidogrel alone, one patient (5.6%) receiving combination therapy with cilostazol (100 mg) and one patient (1.9%) receiving combination therapy with cilostazol (200 mg). The rate of PRU >230 was significantly lower in both of the cilostazol combination groups than in the clopidogrel alone group. The percent inhibition was <20% in 41 patients (32.5%) receiving clopidogrel alone, one patient (5.6%) receiving a combination with cilostazol (100 mg) and one patient (1.9%) receiving a combination with cilostazol (200 mg). The rate of % inhibition <20% was significantly lower in both of the cilostazol combination groups than in the clopidogrel alone group.
  
  
  CONCLUSIONS
  Clopidogrel resistance was clearly decreased with combination clopidogrel (75 mg) and low-dose (100 mg) cilostazol therapy. The use of combination therapy with clopidogrel and low-dose cilostazol may be one means of overcoming clopidogrel resistance.
authors.affiliation: Department of Neurology and Cerebrovascular Medicine, Saitama Medical University International Medical Center, Japan. hmaruyam@saitama-med.ac.jp
authors.forename: Hajime
authors.initials: H
authors.lastname: Maruyama
authors.forename: Takuya
authors.initials: T
authors.lastname: Fukuoka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Deguchi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Ohe
authors.forename: Harumitsu
authors.initials: H
authors.lastname: Nagoya
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kato
authors.forename: Yohsuke
authors.initials: Y
authors.lastname: Horiuchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Norio
authors.initials: N
authors.lastname: Tanahashi
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy*; D000077407:Cilostazol; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects; D012307:Risk Factors; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D013777:Tetrazoles; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000077407:Cilostazol; D013988:Ticlopidine