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Non-antiplatelet effect of clopidogrel: improving endothelial function in Chinese healthy subjects with different

Yin-Zhuang Zhang1, Bi-Lian Chen, Wei Zhang

  • 1Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Clinical and Experimental Pharmacology & Physiology
|October 15, 2014
PubMed

Insights

Clopidogrel improved endothelial function in healthy Chinese subjects, regardless of CYP2C19 genotype. This vascular benefit was independent of clopidogrel's antiplatelet effects, suggesting a distinct mechanism of action.

Area of Science:

  • Pharmacology
  • Cardiovascular Medicine
  • Genetics

Background:

  • Clopidogrel is known to improve endothelial function.
  • The influence of CYP2C19 genetic variations on clopidogrel's endothelial effects is not well understood.
  • CYP2C19 genotype affects clopidogrel's antiplatelet efficacy.

Purpose of the Study:

  • To investigate whether clopidogrel's improvement of endothelial function is associated with CYP2C19 polymorphisms.
  • To determine if clopidogrel's effect on endothelial function is independent of its antiplatelet action.

Main Methods:

  • 12 healthy Chinese participants were genotyped for CYP2C19 polymorphisms (extensive metabolizers [EM] vs. poor metabolizers [PM]).
  • Participants received a 300 mg oral dose of clopidogrel.
  • Endothelial function was assessed via flow-mediated dilation (FMD) of the brachial artery.
  • Adenosine diphosphate (ADP)-induced platelet aggregation was measured using optical aggregometry.

Main Results:

  • Clopidogrel significantly improved FMD at 4 and 24 hours in both EM and PM groups, with no significant difference between groups.
  • ADP-induced platelet aggregation was significantly inhibited in the EM group at 4 and 24 hours, but not in the PM group.
  • No statistical correlation was found between changes in FMD and platelet aggregation within either CYP2C19 group.

Conclusions:

  • Clopidogrel enhances endothelial function in healthy Chinese subjects.
  • This improvement in endothelial function is independent of CYP2C19 genotype.
  • The vascular benefits of clopidogrel are not directly linked to its antiplatelet activity in this population.

Keywords:
CYP2C19 genotypeclopidogrelendothelial functionflow-mediated dilation

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