High loading dose of clopidogrel is unable to satisfactorily inhibit platelet reactivity in patients with glycoprotein IIIA gene polymorphism: a genetic substudy of PRAGUE-8 trial
Jazyk angličtina Země Anglie, Velká Británie Médium print
Typ dokumentu srovnávací studie, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem
- MeSH
- adenosindifosfát farmakologie MeSH
- aktivace trombocytů účinky léků genetika MeSH
- antigeny trombocytů genetika MeSH
- časové faktory MeSH
- inhibitory agregace trombocytů aplikace a dávkování MeSH
- integrin beta3 genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- klopidogrel MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci koronárních tepen farmakoterapie genetika MeSH
- senioři MeSH
- tiklopidin aplikace a dávkování analogy a deriváty MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Názvy látek
- adenosindifosfát MeSH
- antigeny trombocytů MeSH
- human platelet antigen 1b MeSH Prohlížeč
- inhibitory agregace trombocytů MeSH
- integrin beta3 MeSH
- ITGB3 protein, human MeSH Prohlížeč
- klopidogrel MeSH
- tiklopidin MeSH
The study aimed to assess the impact of nine polymorphisms of genes encoding platelet receptors, enzymes, and hemostatic factors on clopidogrel efficacy to inhibit platelet reactivity in patients with stable coronary artery disease undergoing elective coronary angiography either with or without ad hoc percutaneous coronary intervention. The study was performed as a genetic substudy of the PRAGUE-8 trial. Ninety-five patients pretreated with 600 mg clopidogrel at least 6 h prior to coronary angiography were tested. Baseline platelet reactivity to ADP was assessed before the drug was administered. Clopidogrel efficacy was tested again at 12 and 28 h after administration. Polymorphisms of platelet receptors, glycoprotein (GP) Ia (807C/T), GPVI (13254C/T), GPIIIa (PlA1/PlA2), PAR-1 (IVSn-14A/T), P2Y12 (32C/T), P2Y12 (H1/H2) haplotype, gene variations of cyclooxygenase-1, Leiden, and factor II mutations were studied. Flow cytometric tests of vasodilator-stimulated phosphoprotein phosphorylation states were used as a measure of drug efficacy. None of the gene polymorphisms influenced baseline ADP-induced platelet reactivity significantly. Twenty-eight hours after drug administration, differences in suppression of ADP-induced platelet reactivity were observed between polymorphism-positive and polymorphism-negative patients. Inhibition of platelet reactivity, after 600 mg of clopidogrel, was significantly less in carriers of PlA2 (P=0.009) for mean decrease in platelet reactivity index. The proportion of clopidogrel nonresponders (platelet reactivity index >50%) was apparently higher in PlA2 carriers in comparison with PlA1/PlA1 patients (54 vs. 24%, P=0.082). A 600 mg loading dose of clopidogrel failed to acceptably inhibit platelet reactivity in patients who were positive for the PlA2 polymorphism.
Citace poskytuje Crossref.org
