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

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dc.contributor.authorLatkovskis, Gustavs
dc.contributor.authorUrtane, Inga
dc.contributor.authorKnipse, Agnese
dc.contributor.authorPeculis, Raitis
dc.contributor.authorCakstina, Inese
dc.contributor.authorKlovins, Janis
dc.contributor.authorErglis, Andrejs
dc.contributor.institutionFaculty of Pharmacy
dc.date.accessioned2021-04-30T08:20:01Z
dc.date.available2021-04-30T08:20:01Z
dc.date.issued2014
dc.descriptionFunding Information: Financial support of European Social Fund project “Support for doctoral students in acquiring study program and acquisition of the scientific degree in Riga Stradins University” (No. 2009/0147/1DP/1.1.2.1.2/09/IPIA/VIAA/009). Work was supported by European Regional Development Fund Project (2010/0311/2DP/2.1.1.1.0/10/APIA/VIAA/069). We acknowledge Genome Database of Latvian Population, Latvian Biomedical Research and Study Centre for providing genetic data and DNA samples. Publisher Copyright: © 2014 Lithuanian University of Health Sciences. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.
dc.description.abstractBackground 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.en
dc.description.statusPeer reviewed
dc.format.extent9
dc.format.extent906109
dc.identifier.citationLatkovskis, G, Urtane, I, Knipse, A, Peculis, R, Cakstina, I, Klovins, J & Erglis, A 2014, 'Role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsiveness', Medicina (Lithuania), vol. 50, no. 1, pp. 19-27. https://doi.org/10.1016/j.medici.2014.05.004
dc.identifier.doi10.1016/j.medici.2014.05.004
dc.identifier.issn1010-660X
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/4000
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=84906960660&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofMedicina (Lithuania)
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectABCB1
dc.subjectClopidogrel resistance
dc.subjectCYP2C19
dc.subjectCYP2C9
dc.subjectVASP
dc.subject3.2 Clinical medicine
dc.subject3.1 Basic medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectGeneral Medicine
dc.titleRole of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsivenessen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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