Impact of the CYP2C19*17 Allele on Outcomes in Patients Receiving Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.
Impact of the CYP2C19*17 Allele on Outcomes in Patients Receiving Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.
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CYP2C19*17等位基因对经皮冠状动脉介入治疗后接受基因型指导抗血小板治疗患者结局的影响
DOI：
10.1002/cpt.2039
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发表时间：
2021-03
影响因子：
6.7
通讯作者：
IGNITE Network Pharmacogenetics Working Group
中科院分区：
文献类型：
--
作者：
Lee CR;Thomas CD;Beitelshees AL;Tuteja S;Empey PE;Lee JC;Limdi NA;Duarte JD;Skaar TC;Chen Y;Cook KJ;Coons JC;Dillon C;Franchi F;Giri J;Gong Y;Kreutz RP;McDonough CW;Stevenson JM;Weck KE;Angiolillo DJ;Johnson JA;Stouffer GA;Cavallari LH;IGNITE Network Pharmacogenetics Working Group
CYP 2C 19无功能等位基因基因分型指导经皮冠状动脉介入治疗（PCI）后抗血小板治疗可改善临床结局。尽管也报告了CYP 2C 19 *17等位基因功能增加的结果，但其在这种情况下的临床相关性仍不清楚。9个研究中心的合作检查了3，342例患者在实施CYP 2C 19指导的抗血小板治疗后的抗血小板治疗处方和临床结局。通过比例风险回归，比较了CYP 2C 19代谢表型和抗血小板治疗组PCI后12个月内主要动脉粥样硬化血栓形成和出血事件的风险。氯吡格雷处方给药的CYP 2C 19正常（84.5%）、快速（82.9%）和超快速代谢者（80.6%）比例相似（P=0.360）。氯吡格雷治疗的正常代谢者（20.4起事件/100患者-年;校正的风险比[HR] 1.00，95%置信区间[CI] 0.75-1.33，P=0.993）和氯吡格雷治疗的快速或超快速代谢者（19.1起事件/100患者-年;校正的HR 0.95，95% CI 0.69-1.30，P=0.734）与普拉格雷或替格瑞洛治疗的患者（17.6起事件/100患者-年）相比，在主要动脉粥样硬化血栓形成事件方面没有差异。相比之下，氯吡格雷治疗的中代谢型和弱代谢型患者与普拉格雷/替格瑞洛治疗的患者相比，动脉粥样硬化血栓形成事件风险显著更高（校正HR 1.56，95% CI 1.12-2.16，P=0.008）。当比较氯吡格雷治疗的快速或超快速代谢者与正常代谢者时，未观察到动脉粥样硬化血栓形成（校正HR 0.97，95% CI 0.73-1.29，P=0.808）或出血事件（校正HR 1.34，95% CI 0.83-2.17，P=0.224）的差异。在基因型指导抗血小板治疗的现实环境中，CYP 2C 19 *17等位基因对PCI后处方决策或临床结局无显著影响。这些结果表明，CYP 2C 19 *1/*17和 *17/*17基因型在指导PCI后抗血小板治疗方面的临床效用有限。
Genotyping for CYP2C19 no function alleles to guide antiplatelet therapy after percutaneous coronary intervention (PCI) improves clinical outcomes. Although results for the increased function CYP2C19*17 allele are also reported, its clinical relevance in this setting remains unclear. A collaboration across nine sites examined antiplatelet therapy prescribing and clinical outcomes in 3,342 patients after implementation of CYP2C19-guided antiplatelet therapy. Risk of major atherothrombotic and bleeding events over 12 months after PCI were compared across CYP2C19 metabolizer phenotype and antiplatelet therapy groups by proportional hazards regression. Clopidogrel was prescribed to a similar proportion of CYP2C19 normal (84.5%), rapid (82.9%) and ultrarapid metabolizers (80.6%) (P=0.360). Clopidogrel-treated normal metabolizers (20.4 events/100 patient-years; adjusted hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.75–1.33, P=0.993) and clopidogrel-treated rapid or ultrarapid metabolizers (19.1 events/100 patient-years; adjusted HR 0.95, 95% CI 0.69–1.30, P=0.734) exhibited no difference in major atherothrombotic events compared to patients treated with prasugrel or ticagrelor (17.6 events/100 patient-years). In contrast, clopidogrel-treated intermediate and poor metabolizers exhibited significantly higher atherothrombotic event risk compared to prasugrel/ticagrelor-treated patients (adjusted HR 1.56, 95% CI 1.12–2.16, P=0.008). When comparing clopidogrel-treated rapid or ultrarapid metabolizers to normal metabolizers, no difference in atherothrombotic (adjusted HR 0.97, 95% CI 0.73–1.29, P=0.808) or bleeding events (adjusted HR 1.34, 95% CI 0.83–2.17, P=0.224) were observed. In a real-world setting of genotype-guided antiplatelet therapy, the CYP2C19*17 allele did not significantly impact post-PCI prescribing decisions or clinical outcomes. These results suggest the CYP2C19 *1/*17 and *17/*17 genotypes have limited clinical utility to guide antiplatelet therapy after PCI.
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影响因子：
6.7
作者：
通讯作者：
--
DOI：
10.1161/circgen.117.002069
发表时间：
2018-04
期刊：
Circulation. Genomic and precision medicine
影响因子：
--
作者：
Lee CR;Sriramoju VB;Cervantes A;Howell LA;Varunok N;Madan S;Hamrick K;Polasek MJ;Lee JA;Clarke M;Cicci JD;Weck KE;Stouffer GA
通讯作者：
Stouffer GA
影响因子：
4.1
作者：
Pratt, Victoria M.;Del Tredici, Andria L.;Weck, Karen E.
通讯作者：
Weck, Karen E.
降低功能的CYP2C19基因型和氯吡格雷治疗的患者中主要患有PCI的患者的不良临床结局的风险：一项荟萃分析。
DOI：
10.1001/jama.2010.1543
发表时间：
2010-10-27
期刊：
JAMA
影响因子：
--
作者：
Mega JL;Simon T;Collet JP;Anderson JL;Antman EM;Bliden K;Cannon CP;Danchin N;Giusti B;Gurbel P;Horne BD;Hulot JS;Kastrati A;Montalescot G;Neumann FJ;Shen L;Sibbing D;Steg PG;Trenk D;Wiviott SD;Sabatine MS
通讯作者：
Sabatine MS
影响因子：
37.8
作者：
Mega, Jessica L.;Close, Sandra L.;Sabatine, Marc S.
通讯作者：
Sabatine, Marc S.