Impact of CYP2C19 variants on clinical efficacy of clopidogrel and one-year clinical outcomes in coronary heart patients undergoing percutaneous coronary intervention
The impact of pharmacogenetic variants of cytochrome P450 2C19 (CYP2C19) on clopidogrel-mediated effects on platelet inhibition, inflammatory response and endothelial function, as well as risk of major adverse cardiovascular events (MACE), in coronary heart patients undergoing percutaneous coronary...
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| Format: | Article |
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Frontiers Media S.A.
2016-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00453/full |
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| author | Hong Sun Hong Sun Qiang Qu Zhen Fan Chen Sheng-Lan Tan Hai-Jun Zhou Jian Qu Hui Chen |
| author_facet | Hong Sun Hong Sun Qiang Qu Zhen Fan Chen Sheng-Lan Tan Hai-Jun Zhou Jian Qu Hui Chen |
| author_sort | Hong Sun |
| collection | DOAJ |
| description | The impact of pharmacogenetic variants of cytochrome P450 2C19 (CYP2C19) on clopidogrel-mediated effects on platelet inhibition, inflammatory response and endothelial function, as well as risk of major adverse cardiovascular events (MACE), in coronary heart patients undergoing percutaneous coronary intervention (PCI) was investigated. To this end, we assessed the residual platelet aggregation rate (RPA), maximal aggregation rate (MAR) and plasma levels of sCD40L, sP-selectin, MMP-9, sVCAM-1 and sE-selectin after 24 h of PCI in 559 patients treated with clopidogrel and followed up for one year for evidence of MACE. CYP2C19 *2 and *3 variants were identified using a clopidogrel-sensitive gene detection kit. Our results showed higher RPA and MAR as well as increased sE-selectin, sCD40L, sP-selectin, MMP-9 and sVCAM-1 levels in CYP2C19 intermediate metabolizer (IM, CYP2C19*1/*2 or *1/*3), poor metabolizer (PM, CYP2C19*2/*2, *2/*3 or *3/*3) and combined IM+PM groups, relative to those in extensive metabolizers (EM, CYP2C19*1/*1). In total, 519 patients completed one year of follow-up, among which 69 (13.3%) experienced MACE. The risk of MACE in CYP2C19 IM+PM patients was 2.664 times higher than that in CYP2C19 EM patients (OR=2.664(1.397–5.193), P=0.004). The data suggest that CYP2C19*2 and *3 variants modulate the drug efficacy of clopidogrel in coronary heart patients undergoing PCI and further enhance the risk of MACE. Accordingly, CYP2C19 pharmacogenetic profiling may be beneficial for coronary heart patients undergoing PCI to predict the efficacy of treatment with clopidogrel. We propose that IM and PM patients should benefit from treatment with higher clopidogrel doses to improve efficacy and reduce the incidence of MACE. |
| first_indexed | 2024-04-13T03:39:15Z |
| format | Article |
| id | doaj.art-e325cf8395cc4835bfc95229dc8eba58 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T03:39:15Z |
| publishDate | 2016-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-e325cf8395cc4835bfc95229dc8eba582022-12-22T03:04:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122016-11-01710.3389/fphar.2016.00453211071Impact of CYP2C19 variants on clinical efficacy of clopidogrel and one-year clinical outcomes in coronary heart patients undergoing percutaneous coronary interventionHong Sun0Hong Sun1Qiang Qu2Zhen Fan Chen3Sheng-Lan Tan4Hai-Jun Zhou5Jian Qu6Hui Chen7the Second Xiangya Hospital,Central South UniversityProvincial Clinical College of Fujian Medical University, Fujian Provincial HospitalXiangya Hospital, Central South UniversityProvincial Clinical College of Fujian Medical University, Fujian Provincial Hospitalthe Second Xiangya Hospital,Central South UniversityProvincial Clinical College of Fujian Medical University, Fujian Provincial Hospitalthe Second Xiangya Hospital,Central South UniversityHypertension Laboratory, Provincial Clinical College of Fujian Medical University, Fujian Provincial Cardiovascular Disease Institute, Fujian Provincial HospitalThe impact of pharmacogenetic variants of cytochrome P450 2C19 (CYP2C19) on clopidogrel-mediated effects on platelet inhibition, inflammatory response and endothelial function, as well as risk of major adverse cardiovascular events (MACE), in coronary heart patients undergoing percutaneous coronary intervention (PCI) was investigated. To this end, we assessed the residual platelet aggregation rate (RPA), maximal aggregation rate (MAR) and plasma levels of sCD40L, sP-selectin, MMP-9, sVCAM-1 and sE-selectin after 24 h of PCI in 559 patients treated with clopidogrel and followed up for one year for evidence of MACE. CYP2C19 *2 and *3 variants were identified using a clopidogrel-sensitive gene detection kit. Our results showed higher RPA and MAR as well as increased sE-selectin, sCD40L, sP-selectin, MMP-9 and sVCAM-1 levels in CYP2C19 intermediate metabolizer (IM, CYP2C19*1/*2 or *1/*3), poor metabolizer (PM, CYP2C19*2/*2, *2/*3 or *3/*3) and combined IM+PM groups, relative to those in extensive metabolizers (EM, CYP2C19*1/*1). In total, 519 patients completed one year of follow-up, among which 69 (13.3%) experienced MACE. The risk of MACE in CYP2C19 IM+PM patients was 2.664 times higher than that in CYP2C19 EM patients (OR=2.664(1.397–5.193), P=0.004). The data suggest that CYP2C19*2 and *3 variants modulate the drug efficacy of clopidogrel in coronary heart patients undergoing PCI and further enhance the risk of MACE. Accordingly, CYP2C19 pharmacogenetic profiling may be beneficial for coronary heart patients undergoing PCI to predict the efficacy of treatment with clopidogrel. We propose that IM and PM patients should benefit from treatment with higher clopidogrel doses to improve efficacy and reduce the incidence of MACE.http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00453/fullantiplatelet therapyclopidogrelCYP2C19PCIMetabolizers |
| spellingShingle | Hong Sun Hong Sun Qiang Qu Zhen Fan Chen Sheng-Lan Tan Hai-Jun Zhou Jian Qu Hui Chen Impact of CYP2C19 variants on clinical efficacy of clopidogrel and one-year clinical outcomes in coronary heart patients undergoing percutaneous coronary intervention Frontiers in Pharmacology antiplatelet therapy clopidogrel CYP2C19 PCI Metabolizers |
| title | Impact of CYP2C19 variants on clinical efficacy of clopidogrel and one-year clinical outcomes in coronary heart patients undergoing percutaneous coronary intervention |
| title_full | Impact of CYP2C19 variants on clinical efficacy of clopidogrel and one-year clinical outcomes in coronary heart patients undergoing percutaneous coronary intervention |
| title_fullStr | Impact of CYP2C19 variants on clinical efficacy of clopidogrel and one-year clinical outcomes in coronary heart patients undergoing percutaneous coronary intervention |
| title_full_unstemmed | Impact of CYP2C19 variants on clinical efficacy of clopidogrel and one-year clinical outcomes in coronary heart patients undergoing percutaneous coronary intervention |
| title_short | Impact of CYP2C19 variants on clinical efficacy of clopidogrel and one-year clinical outcomes in coronary heart patients undergoing percutaneous coronary intervention |
| title_sort | impact of cyp2c19 variants on clinical efficacy of clopidogrel and one year clinical outcomes in coronary heart patients undergoing percutaneous coronary intervention |
| topic | antiplatelet therapy clopidogrel CYP2C19 PCI Metabolizers |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00453/full |
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