Role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsiveness
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....
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-01-01
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| Series: | Medicina |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1010660X14000056 |
| _version_ | 1797728364801294336 |
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| author | Gustavs Latkovskis Inga Urtane Agnese Knipse Raitis Peculis Inese Cakstina Janis Klovins Andrejs Erglis |
| author_facet | Gustavs Latkovskis Inga Urtane Agnese Knipse Raitis Peculis Inese Cakstina Janis Klovins Andrejs Erglis |
| author_sort | Gustavs Latkovskis |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T11:12:55Z |
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| id | doaj.art-bb8fd6494d1645b9a2a4c790d1046138 |
| institution | Directory Open Access Journal |
| issn | 1010-660X |
| language | English |
| last_indexed | 2024-03-12T11:12:55Z |
| publishDate | 2014-01-01 |
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| series | Medicina |
| spelling | doaj.art-bb8fd6494d1645b9a2a4c790d10461382023-09-02T02:32:43ZengMDPI AGMedicina1010-660X2014-01-01501192710.1016/j.medici.2014.05.004Role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsivenessGustavs Latkovskis0Inga Urtane1Agnese Knipse2Raitis Peculis3Inese Cakstina4Janis Klovins5Andrejs Erglis6Latvian Centre of Cardiology, Paul Stradins Clinical University Hospital, Riga, LatviaFaculty of Pharmacy, Riga Stradins University, Riga, LatviaLatvian Centre of Cardiology, Paul Stradins Clinical University Hospital, Riga, LatviaLatvian Biomedical Research and Study Centre, Riga, LatviaCell Transplantation Centre, Paul Stradins Clinical University Hospital, Riga, LatviaLatvian Biomedical Research and Study Centre, Riga, LatviaLatvian Centre of Cardiology, Paul Stradins Clinical University Hospital, Riga, LatviaBackground 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.http://www.sciencedirect.com/science/article/pii/S1010660X14000056Clopidogrel resistanceVASPCYP2C19ABCB1CYP2C9 |
| spellingShingle | Gustavs Latkovskis Inga Urtane Agnese Knipse Raitis Peculis Inese Cakstina Janis Klovins Andrejs Erglis Role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsiveness Medicina Clopidogrel resistance VASP CYP2C19 ABCB1 CYP2C9 |
| title | Role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsiveness |
| title_full | Role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsiveness |
| title_fullStr | Role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsiveness |
| title_full_unstemmed | Role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsiveness |
| title_short | Role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsiveness |
| title_sort | role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsiveness |
| topic | Clopidogrel resistance VASP CYP2C19 ABCB1 CYP2C9 |
| url | http://www.sciencedirect.com/science/article/pii/S1010660X14000056 |
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