title: Effect of cilostazol addition or clopidogrel doubling on platelet function profiles in diabetic patients undergoing a percutaneous coronary intervention.
abstract: BACKGROUND
  We investigated the pharmacodynamic effect of cilostazol addition (100 mg twice, Triple) or clopidogrel doubling (150 mg daily, Double) on standard dual antiplatelet therapy in type 2 diabetes mellitus (T2DM) patients with clopidogrel resistance undergoing a percutaneous coronary intervention.
  
  
  RESULTS
  This was a prospective, randomized, cross-over platelet function study. Percent inhibition less than 20% was used as the cutoff value of clopidogrel resistance. After percutaneous coronary intervention, a total of 50 T2DM patients with clopidogrel resistance were assigned to receive cilostazol 100 mg twice daily or clopidogrel 150 mg daily for 28 days; afterwards, they received cross-over treatment for another 28 days. Eight patients were excluded because of side effects and follow-up loss. The platelet function test using VerifyNow was performed at three time points: at baseline (T0), 28 days after randomization (T1), and 28 days after cross-over treatment (T2).A total of 42 T2DM patients completed the study protocol. The clopidogrel resistance improved significantly following cilostazol addition or clopidogrel doubling treatment compared with baseline (52.9±27.0 in Triple, 45.4±16.8% in Double, P<0.001 in both). This effect continued after cross-over treatment (58.1±26.1 and 41.0±20.0%, respectively, both P<0.05). A head-to-head comparison between two groups showed a lower P2Y12 reaction unit (PRU) and higher percentage of platelet inhibition in the Triple than those in the Double group (PRU, 138.7±88.2 vs. 198.8±19.5, P=0.049; %platelet inhibition, 58.1±26.1 vs. 40.97±20.0, P=0.048).
  
  
  CONCLUSIONS
  Adjunctive treatment with cilostazol in T2DM patients on standard dual antiplatelet therapy might be a more effective strategy for overcoming clopidogrel resistance than clopidogrel doubling treatment.
authors.affiliation: aDepartment of Internal Medicine, School of Medicine, Division of Cardiology, Kyung Hee University bCardiovascular Center, Kyung Sang University, Seoul, Korea.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Ha
authors.forename: Soo-Joong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Seok-Jae
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Jong Shin
authors.initials: JS
authors.lastname: Woo
authors.forename: Weon
authors.initials: W
authors.lastname: Kim
authors.forename: Woo-Shik
authors.initials: WS
authors.lastname: Kim
authors.forename: Kwon Sam
authors.initials: KS
authors.lastname: Kim
authors.forename: Myeong Kon
authors.initials: MK
authors.lastname: Kim
mesh_terms: D001792:Blood Platelets / Q000187:drug effects*; D000077407:Cilostazol; D000077144:Clopidogrel; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D006801:Humans; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D011446:Prospective Studies; D056910:Republic of Korea; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077144:Clopidogrel; D000077407:Cilostazol; D013988:Ticlopidine