Cilostazol added to aspirin and clopidogrel reduces revascularization without increases in major adverse events in patients with drug-eluting stents: a meta-analysis of randomized controlled trials

Int J Cardiol. 2013 Sep 1;167(5):2250-8. doi: 10.1016/j.ijcard.2012.06.010. Epub 2012 Jun 22.

Abstract

Background: The effects of cilostazol added to aspirin and clopidogrel (triple antiplatelet therapy: TAT) on clinical outcomes after drug-eluting stent (DES) implantation are unknown.

Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) comparing TAT with aspirin and clopidogrel (dual antiplatelet therapy: DAT) in DES patients. Clinical end points were target lesion (TLR) and/or vessel (TVR) revascularization, death, myocardial infarction (MI), stent thrombosis (ST), bleeding, rash, gastrointestinal (GI) side effects, and drug discontinuation. We calculated the pooled estimate based on a fixed-effects model using Peto odds ratio (OR) for rare events. If heterogeneity was observed across an individual RCT, an analysis based on a random-effects model was performed.

Results: Eight RCTs were included in this meta-analysis, involving 3590 patients (TAT:DAT=1800:1790). Up to 24 months, TAT showed a significant reduction in TLR (OR: 0.58, 95% confidence interval (CI): 0.43 to 0.78, p<0.001) and TVR (OR: 0.58, 95% CI: 0.40 to 0.83, p=0.003) compared with DAT. The incidence of death, MI, ST, or overall or major bleeding was comparable between the 2 groups, whereas the proportion of rash (OR: 2.50, 95% CI: 1.52 to 4.10, p<0.001), GI side effects (OR: 3.14, 95% CI: 1.79 to 5.50, p<0.001), or drug discontinuation (OR: 6.81, 95% CI: 2.12 to 21.86, p<0.001) was higher in TAT than DAT.

Conclusions: In this meta-analysis, TAT was associated with significantly effective outcomes for TLR and TVR without any increase in major adverse events but was associated with tolerance issues compared with DAT after DES implantation.

Keywords: Cilostazol; Drug-eluting stent; Meta-analysis; Randomized controlled trial; Triple antiplatelet therapy.

Publication types

  • Meta-Analysis

MeSH terms

  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / therapy
  • Cilostazol
  • Clopidogrel
  • Coronary Restenosis / epidemiology
  • Coronary Restenosis / prevention & control*
  • Drug Therapy, Combination
  • Drug-Eluting Stents* / adverse effects
  • Humans
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Randomized Controlled Trials as Topic / methods
  • Tetrazoles / administration & dosage*
  • Tetrazoles / adverse effects
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*

Substances

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