The impact of clinical and genetic factors on ticagrelor and clopidogrel antiplatelet therapy

Pharmacogenomics. 2017 Jul;18(10):969-979. doi: 10.2217/pgs-2017-0070. Epub 2017 Jun 12.

Abstract

Aim: To determine clinically significant factors which may alter the effect of dual antiplatelet therapy with aspirin and ticagrelor or clopidogrel in patients who had undergone percutaneous coronary intervention and stent implantation.

Materials & methods: The study included 378 patients. All the patients had undergone percutaneous coronary intervention and stent implantation. Platelet aggregation and genotyping for CYP2C19 *2 (rs4244285) and CYP4F2 (rs2108622, rs1558139, rs3093135 and rs2074902) was performed.

Results: Significantly lower platelet aggregation values (%agr) were detected in ticagrelor users who carried CYP4F2 rs3093135 TT variant (14.67 ± 5.07%agr) versus AA (22.88 ± 6.30%agr), p = 0.0004, or AT (20.56 ± 6.51%agr), p = 0.0126.

Conclusion: Results of the current study showed that CYP4F2 rs3093135 TT variant carriers had a higher antiplatelet effect of ticagrelor, and more frequently had nonprocedural bleeding during ticagrelor therapy, as compared with AA and AT variant carriers.

Keywords: STEMI; clopidogrel therapy; ticagrelor pharmacogenomics.

MeSH terms

  • Adenosine / administration & dosage
  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacokinetics
  • Adenosine / therapeutic use
  • Aged
  • Clopidogrel
  • Cytochrome P450 Family 4 / genetics*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Hemorrhage / genetics
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention
  • Pharmacogenomic Variants*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / genetics
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Ticagrelor
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics
  • Ticlopidine / therapeutic use
  • Time Factors

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Cytochrome P450 Family 4
  • CYP4F2 protein, human
  • Ticagrelor
  • Adenosine
  • Ticlopidine