title: Inhibitory interaction between calcium channel blocker and clopidogrel. -Efficacy of cilostazol to overcome it-.
abstract: BACKGROUND
  The clinical effect of, and additive measures to overcome the possible inhibitory calcium channel blocker (CCB)-clopidogrel interaction in Asian patients undergoing percutaneous coronary intervention is unknown.
  
  
  RESULTS
  A total of 900 Korean patients enrolled for the multicenter, prospective, randomized Influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation (CILON-T) trial were divided into 4 groups depending on CCB prescription and type of anti-platelet therapy (dual [DAT] vs. triple [TAT; addition of cilostazol to DAT]) in a 2 × 2 factorial manner. The primary endpoint was a composite of cardiac death, non-fatal myocardial infarction and ischemic stroke at 6 months after PCI. On-treatment platelet reactivity (OPR) was assessed on VerifyNow P2Y12 assay. Concomitant CCB use increased OPR in the DAT group (mean ± SEM: 251.2 ± 7.6 vs. 225.6 ± 5.1; P=0.008), but not in the TAT group (214.5±9.1 vs. 203.4 ± 5.6; P=0.294). Primary endpoint increased by use of CCB in patients with DAT (4.9% vs. 0.9%, P=0.016), but not in those with TAT (0% vs. 1.8%, P=0.346). Addition of cilostazol to DAT reduced OPR and clinical events in patients taking CCB (P=0.007 for P2Y12 reaction units; P=0.027 for thrombotic events). CCB without concomitant cilostazol use was a significant predictor of total thrombotic events.
  
  
  CONCLUSIONS
  Concomitant use of CCB may weaken the anti-platelet effect of clopidogrel and increase subsequent thrombotic events in Asian subjects. This hazardous CCB-clopidogrel interaction may be overcome by addition of cilostazol.
authors.affiliation: Cardiovascular Center, Department of Internal Medicine, Seoul National University Hospital.
authors.forename: Seung-Pyo
authors.initials: SP
authors.lastname: Lee
authors.forename: Jang-Whan
authors.initials: JW
authors.lastname: Bae
authors.forename: Kyung Woo
authors.initials: KW
authors.lastname: Park
authors.forename: Seung-Woon
authors.initials: SW
authors.lastname: Rha
authors.forename: Jang-Ho
authors.initials: JH
authors.lastname: Bae
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Suh
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Chae
authors.forename: Myeong-Chan
authors.initials: MC
authors.lastname: Cho
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000209:etiology / Q000401:mortality; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects; D000077407:Cilostazol; D000077144:Clopidogrel; D003643:Death; D004336:Drug Antagonism; D054855:Drug-Eluting Stents / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D020521:Stroke / Q000209:etiology / Q000401:mortality; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors
chemical_list: D002121:Calcium Channel Blockers; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077144:Clopidogrel; D000077407:Cilostazol; D013988:Ticlopidine