Randomized Comparison of Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With High Post-Treatment Platelet Reactivity: Results of the ACCEL-RESISTANCE (Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With Clopidogrel Resistance) Randomized Study

J Am Coll Cardiol. 2009 Mar 31;53(13):1101-9. doi: 10.1016/j.jacc.2008.12.025.

Abstract

Objectives: The purpose of this study was to determine the impact of adjunctive cilostazol in patients with high post-treatment platelet reactivity (HPPR) undergoing coronary stenting.

Background: Although addition of cilostazol to dual antiplatelet therapy enhances adenosine diphosphate (ADP)-induced platelet inhibition, it is unknown whether adjunctive cilostazol can reduce HPPR.

Methods: Sixty patients with HPPR after a 300-mg loading dose of clopidogrel were enrolled. HPPR was defined as maximal platelet aggregation (Agg(max)) >50% with 5 micromol/l ADP. Patients were randomly assigned to receive either adjunctive cilostazol (triple group; n = 30) or high maintenance dose (MD) clopidogrel (high-MD group; n = 30). Platelet function was assessed at baseline and after 30 days with conventional aggregometry and the VerifyNow assay.

Results: Baseline platelet function measurements were similar in both groups. After 30 days, significantly fewer patients in the triple versus high-MD group had HPPR (3.3% vs. 26.7%, p = 0.012). Percent inhibitions of 5 micromol/l ADP-induced Agg(max) and late platelet aggregation (Agg(late)) were significantly greater in the triple versus high-MD group (51.1 +/- 22.5% vs. 28.0 +/- 18.5%, p < 0.001, and 70.9 +/- 27.3% vs. 45.3 +/- 23.4%, p < 0.001, respectively). Percent inhibitions of 20 micromol/l ADP-induced Agg(max) and Agg(late) were consistently greater in the triple versus high-MD group. Percent change of P2Y12 reaction units demonstrated a higher antiplatelet effect in the triple versus high-MD group (39.6 +/- 24.1% vs. 23.1 +/- 29.9%, p = 0.022).

Conclusions: Adjunctive cilostazol reduces the rate of HPPR and intensifies platelet inhibition as compared with a high-MD clopidogrel of 150 mg/day.

Publication types

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

MeSH terms

  • Cilostazol
  • Clopidogrel
  • Coronary Disease / therapy
  • Drug Resistance
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Prospective Studies
  • Stents
  • Tetrazoles / administration & dosage*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*

Substances

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