Investigating the Effect of Demographics, Clinical Characteristics, and Polymorphism of MDR-1, CYP1A2, CYP3A4, and CYP3A5 on Clopidogrel Resistance

J Cardiovasc Pharmacol. 2018 Dec;72(6):296-302. doi: 10.1097/FJC.0000000000000627.

Abstract

Clopidogrel is an antiplatelet agent that is indicated for cardiovascular emergencies and procedures. The drug, however, is subject to response variability leading to therapy resistance. In this research, we explored the demographic, clinical, and genetic factors associated with clopidogrel resistance. Data analysis among our 280 subjects receiving clopidogrel showed some risk factors that are significantly associated with clopidogrel resistance compared with responders. Those were: female sex (P = 0.021), advanced age (P = 0.011), obesity (P = 0.002), and higher body mass index (P = 0.008) and higher platelets count (P = 0.002). However, known polymorphisms of MDR-1, CYP1A2, CYP3A4, and CYP3A5 were not associated with treatment resistance when compared to responders to clopidogrel therapy. Knowledge about such risk factors might provide recommendation in the future about starting doses or monitoring recommendations.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Age Factors
  • Aged
  • Body Mass Index
  • Clopidogrel / adverse effects
  • Clopidogrel / metabolism
  • Clopidogrel / therapeutic use*
  • Cytochrome P-450 CYP1A2 / genetics*
  • Cytochrome P-450 CYP1A2 / metabolism
  • Cytochrome P-450 CYP3A / genetics*
  • Cytochrome P-450 CYP3A / metabolism
  • Drug Resistance / genetics*
  • Female
  • Gene Frequency
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenomic Variants*
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation / genetics
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / metabolism
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Count
  • Risk Factors
  • Sex Factors

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • CYP1A2 protein, human
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human