Role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsiveness

Gustavs Latkovskis, Inga Urtane, Agnese Knipse, Raitis Peculis, Inese Cakstina, Janis Klovins, Andrejs Erglis

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Background and objective: Additional loading doses and higher maintenance doses (MDs) have been used to overcome hyporesponsiveness of clopidogrel. We aimed to investigate whether genetic polymorphisms of two cytochromes (CYP2C19 and CYP2C9) and ABCB1 modify effect of such dose-adjustment strategy. Materials and methods: We enrolled 118 patients undergoing elective or acute percutaneous coronary intervention (PCI) with drug eluting stent (DES). Platelet reactivity index (PRI) was measured using the vasodilator-stimulated phosphoprotein (VASP) index and a cut-off value of ≥60% was defined as hyporesponsiveness. Polymorphism of two cytochromes (CYP2C19, CYP2C9) and gene ABCB1 were determined. In patients hyporesponsive to the initial LD the dose-adjustment was performed using up to 3 additional 600mg LDs in order to achieve PRI <60%, and both 150mg and 75mg MD were tested at the follow-up. Results: Patients with at least one CYP2C19*2 allele had higher baseline PRI after the initial LD (78.2 ± 13.1 vs. 65.3 ± 19.5, P = 0.005). The PRI reduction with additional LD was significantly smaller in carriers of the CYP2C19*2 (25.2 ± 15.6 vs. 35.5 ± 16.8, P = 0.025) and similar trend was observed with subsequent additional LDs. Both MDs were less effective in presence of CYP2C19*2. Target PRI was, however, more frequently achieved with higher MD even in presence of CYP2C19*2 (in 70.6% vs. 23.5% of hyporesponders, P = 0.008). No such differences were observed for other polymorphisms. Conclusions: In patients hyporesponsive to a routine clopidogrel doses the potency of additional LD and higher MD of clopidogrel is compromised by presence of CYP2C19*2 allele. The dose-adjustment strategy is not affected by ABCB1 C3435T or CYP2C9 genotypes.

Original languageEnglish
Pages (from-to)19-27
Number of pages9
JournalMedicina (Lithuania)
Volume50
Issue number1
DOIs
Publication statusPublished - 2014

Keywords

  • ABCB1
  • Clopidogrel resistance
  • CYP2C19
  • CYP2C9
  • VASP

Field of Science

  • 3.2 Clinical medicine
  • 3.1 Basic medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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