The efficacy and safety of cilostazol as an alternative to aspirin in Chinese patients with aspirin intolerance after coronary stent implantation: a combined clinical study and computational system pharmacology analysis

Acta Pharmacol Sin. 2018 Feb;39(2):205-212. doi: 10.1038/aps.2017.85. Epub 2017 Sep 21.

Abstract

Dual antiplatelet therapy (DAT) with aspirin and clopidogrel is the standard regimen to achieve rapid platelet inhibition and prevent thrombotic events. Currently, little information is available regarding alternative antiplatelet therapy in patients with an allergy or intolerance to aspirin. Although cilostazol is already a common alternative to aspirin in clinical practice in China, its efficacy and safety remain to be determined. We retrospectively analyzed 613 Chinese patients who had undergone primary percutaneous coronary intervention (PCI). Among them, 405 patients received standard DAT (aspirin plus clopidogrel) and 205 patients were identified with intolerance to aspirin and received alternative DAT (cilostazol plus clopidogrel). There were no significant differences between the two groups in their baseline clinical characteristics. The main outcomes of the study included major adverse cardiac events (MACEs) and bleeding events during 12 months of follow-up. The MACEs endpoint was reached in 10 of 205 patients treated with cilostazol (4.9%) and in 34 of 408 patients treated with aspirin (8.3%). No statistically significant difference was observed in MACEs between the two groups. However, patients in the cilostazol group had less restenosis than did patients in the aspirin group (1.5% vs 4.9%, P=0.035). The occurrence of bleeding events tended to be lower in the cilostazol group (0.49% vs 2.7%, P=0.063). These clinical observations were further analyzed using network system pharmacology analysis, and the outcomes were consistent with clinical observations and preclinical data reports. We conclude that in Chinese patients with aspirin intolerance undergoing coronary stent implantation, the combination of clopidogrel with cilostazol may be an efficacious and safe alternative to the standard DAT regimen.

MeSH terms

  • Aged
  • Asian Continental Ancestry Group
  • Aspirin / adverse effects*
  • China
  • Cilostazol
  • Clopidogrel
  • Coronary Restenosis / prevention & control
  • Data Interpretation, Statistical
  • Drug Combinations
  • Drug-Eluting Stents*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Docking Simulation
  • Percutaneous Coronary Intervention*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Retrospective Studies
  • Tetrazoles / administration & dosage
  • Tetrazoles / therapeutic use*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

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