Platelet reactivity in patients with chronic kidney disease receiving adjunctive cilostazol compared with a high-maintenance dose of clopidogrel: results of the effect of platelet inhibition according to clopidogrel dose in patients with chronic kidney disease (PIANO-2 CKD) randomized study

Am Heart J. 2011 Dec;162(6):1018-25. doi: 10.1016/j.ahj.2011.09.003. Epub 2011 Nov 8.


Background: Chronic kidney disease (CKD) is a factor of low response to clopidogrel. We sought to assess the functional impact of cilostazol in CKD patients with undergoing hemodialysis.

Methods: Seventy-four patients with CKD undergoing hemodialysis and percutaneous coronary intervention were enrolled. Patients were randomly assigned to receive clopidogrel (75 mg/d [group 1, n = 24]), high-maintenance dose of clopidogrel (150 mg/d [group 2, n = 25]), or clopidogrel (75 mg/d) with cilostazol (200 mg/d [group 3, n = 25]) for 14 days. Another 50 patients with normal renal function undergoing percutaneous coronary intervention were treated with 75 mg of clopidogrel and served as the control group. Platelet function was evaluated before and after antiplatelet therapy with light transmittance aggregometry and with VerifyNow P2Y12 assay (Accumetrics, San Diego, CA). Platelet activation markers (soluble CD40 ligand and soluble P-selectin) were also assessed.

Results: The baseline platelet function measurements were similar in the 3 groups of patients; however, the CKD groups had significantly higher platelet aggregation activity compared with the control groups. The rate of high on-treatment platelet reactivity was significantly lower in group 3 than in groups 1 and 2 (10% vs 43% vs 32%, respectively; P < .05). After 14 days of antiplatelet therapy, the changes in plasma soluble CD40 ligand and soluble P-selectin levels were significantly higher in group 3 compared with groups 1 and 2 (P < .01); however, there were no significant differences in platelet function and activation markers between groups 1 and 2.

Conclusions: Adjunctive cilostazol improves platelet inhibition compared with 75 or 150 mg of clopidogrel in CKD patients undergoing hemodialysis.

Trial registration: NCT01328470.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angioplasty, Balloon, Coronary
  • Chronic Disease
  • Cilostazol
  • Clopidogrel
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / therapy*
  • Female
  • Humans
  • Kidney Diseases / therapy*
  • Male
  • Middle Aged
  • Platelet Activation / drug effects*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology*
  • Prospective Studies
  • Renal Dialysis
  • Tetrazoles / pharmacology*
  • Ticlopidine / analogs & derivatives


  • Platelet Aggregation Inhibitors
  • Tetrazoles
  • Clopidogrel
  • Cilostazol
  • Ticlopidine

Associated data