Comparison of on-treatment platelet reactivity between triple antiplatelet therapy with cilostazol and standard dual antiplatelet therapy in patients undergoing coronary interventions: a meta-analysis

J Cardiovasc Pharmacol Ther. 2013 Nov;18(6):533-43. doi: 10.1177/1074248413495971. Epub 2013 Jul 19.

Abstract

Background: The recent literature has shown that triple antiplatelet therapy with cilostazol in addition to the standard dual antiplatelet therapy with aspirin and clopidogrel may reduce platelet reactivity and improve clinical outcomes following percutaneous coronary intervention. The purpose of this meta-analysis is to compare the efficacy of triple antiplatelet therapy and dual antiplatelet therapy in regard to on-treatment platelet reactivity.

Methods: Nine studies (n = 2179) comparing on-treatment platelet reactivity between dual antiplatelet therapy (n = 1193) and triple antiplatelet therapy (n = 986) in patients undergoing percutaneous coronary intervention were included. Primary end points were P2Y12 reaction unit (PRU) and platelet reactivity index (PRI). Secondary end points were platelet aggregation with adenosine diphosphate (ADP) 5 and 20 µmol/L and P2Y12% inhibition. Mean difference (MD) and 95% confidence intervals (CI) were computed and 2-sided α error <.05 was considered as a level of significance.

Results: Compared to dual antiplatelet therapy, triple antiplatelet therapy had significantly lower maximum platelet aggregation with ADP 5 µmol/L (MD: -14.4, CI: -21.6 to -7.2, P < .001) and 20 µmol/L (MD: -14.9, CI: -22.9 to -6.8, P < .001), significantly lower PRUs (MD: -45, CI: -59.4 to -30.6, P < .001) and PRI (MD: -26, CI: -36.8 to -15.2, P < .001), and significantly higher P2Y12% inhibition (MD: 18.5, CI: 2.3 to 34.6, P = .025).

Conclusion: Addition of cilostazol to conventional dual antiplatelet therapy significantly lowers platelet reactivity and may explain a decrease in thromboembolic events following coronary intervention; however, additional studies evaluating clinical outcomes will be helpful to determine the benefit of triple antiplatelet therapy.

Keywords: antiplatelet therapy; cilostazol; percutaneous coronary intervention; platelet reactivity.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review

MeSH terms

  • Aspirin / administration & dosage
  • Aspirin / pharmacology
  • Aspirin / therapeutic use
  • Blood Platelets / drug effects
  • Cilostazol
  • Clopidogrel
  • Coronary Artery Disease / therapy
  • Drug Therapy, Combination
  • Humans
  • Percutaneous Coronary Intervention / methods*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Tetrazoles / administration & dosage
  • Tetrazoles / pharmacology
  • Tetrazoles / therapeutic use*
  • Thromboembolism / epidemiology
  • Thromboembolism / prevention & control
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / pharmacology
  • Ticlopidine / therapeutic use

Substances

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