Clinical Outcomes and Sustainability of Using CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.
Clinical Outcomes and Sustainability of Using CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.
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DOI：
10.1161/circgen.117.002069
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发表时间：
2018-04
期刊：
影响因子：
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通讯作者：
Stouffer GA
中科院分区：
文献类型：
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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
CYP2C19功能丧失(LOF)等位基因影响经皮冠状动脉介入治疗(PCI)后的氯吡格雷疗效。在实践中使用CYP2C19基因导引的双重抗血小板治疗(DAPT)选择的可行性、可持续性和临床影响尚不清楚。一项单中心观察性研究在1193名接受了PCI和DAPT的患者中进行，此前实施了一种算法，该算法建议在高危患者中进行CYP2C19检测，并在LOF等位基因携带者中推荐替代DAPT(普拉格雷或替卡格雷)。基因测试和替代DAPT选择的频率是主要的实施终点。通过比例风险回归，比较不同基因型组和DAPT组在12个月内发生主要不良心脑血管事件(MACCE)和临床重大出血事件的风险。在868例(72.8%)患者中，有868例获得了CYP2C19基因。186例(70.7%)LOF等位基因携带者采用替代DAPT治疗。在LOF等位基因携带者中，CYP2C19检测(P<；0.001)和替代使用DAPT(P=0.001)随时间变化。服用氯吡格雷的LOF携带者发生MACCE的风险显著高于替代DAPT(调整后的危险比[HR]4.65，95%可信区间[CI]2.22-10.0，P<；0.001)，而没有LOF等位基因的患者则无显著差异(调整后的HR为1.37，95%可信区间为0.72-2.85，P=0.347)。不同组间的出血事件发生率相似(对数等级P=0.816)。在现实世界中，实施以基因为导向的CYP2C19 DAPT是可行和可持续的，但要保持一贯的高保真水平具有挑战性。在CYP2C19 LOF等位基因携带者中，与使用氯吡格雷相关的MACCE风险更高，这表明在实践中使用基因引导的DAPT可能会改善临床结果。
CYP2C19 loss-of-function (LOF) alleles impair clopidogrel effectiveness after percutaneous coronary intervention (PCI). The feasibility, sustainability and clinical impact of using CYP2C19 genotype-guided dual antiplatelet therapy (DAPT) selection in practice remains unclear. A single-center observational study was conducted in 1193 patients who underwent PCI and received DAPT following implementation of an algorithm that recommends CYP2C19 testing in high-risk patients and alternative DAPT (prasugrel or ticagrelor) in LOF allele carriers. The frequency of genotype testing and alternative DAPT selection were the primary implementation endpoints. Risk of major adverse cardiovascular or cerebrovascular (MACCE) and clinically significant bleeding events over 12 months were compared across genotype and DAPT groups by proportional hazards regression. CYP2C19 genotype was obtained in 868 (72.8%) patients. Alternative DAPT was prescribed in 186 (70.7%) LOF allele carriers. CYP2C19 testing (P<0.001) and alternative DAPT use in LOF allele carriers (P=0.001) varied over time. Risk for MACCE was significantly higher in LOF carriers prescribed clopidogrel versus alternative DAPT (adjusted hazard ratio [HR] 4.65, 95% confidence interval [CI] 2.22–10.0, P<0.001), whereas no significant difference was observed in those without a LOF allele (adjusted HR 1.37, 95% CI 0.72–2.85, P=0.347). Bleeding event rates were similar across groups (log-rank P=0.816). Implementing CYP2C19 genotype-guided DAPT is feasible and sustainable in a real-world setting, but challenging to maintain at a consistently high level of fidelity. The higher risk of MACCE associated with clopidogrel use in CYP2C19 LOF allele carriers suggests that use of genotype-guided DAPT in practice may improve clinical outcomes.