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Medicina is published by MDPI from Volume 54 Issue 1 (2018). Articles in this Issue were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence. Articles are hosted by MDPI on as a courtesy and upon agreement with Lithuanian Medical Association, Lithuanian University of Health Sciences, and Vilnius University.
Open AccessArticle

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

Latvian Centre of Cardiology, Paul Stradins Clinical University Hospital, Riga, Latvia
Latvian Research Institute of Cardiology, Riga, Latvia
Faculty of Medicine, University of Latvia, Riga, Latvia
Faculty of Pharmacy, Riga Stradins University, Riga, Latvia
Latvian Biomedical Research and Study Centre, Riga, Latvia
Cell Transplantation Centre, Paul Stradins Clinical University Hospital, Riga, Latvia
Author to whom correspondence should be addressed.
Medicina 2014, 50(1), 19-27;
Published: 6 June 2014
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 600 mg LDs in order to achieve PRI <60%, and both 150 mg and 75 mg 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.
Keywords: Clopidogrel resistance; VASP; CYP2C19; ABCB1; CYP2C9 Clopidogrel resistance; VASP; CYP2C19; ABCB1; CYP2C9
MDPI and ACS Style

Latkovskis, G.; Urtane, I.; Knipse, A.; Peculis, R.; Cakstina, I.; Klovins, J.; Erglis, A. Role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsiveness. Medicina 2014, 50, 19-27.

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