Clopidogrel Versus Ticagrelor or Prasugrel After Primary Percutaneous Coronary Intervention According to CYP2C19 Genotype A POPular Genetics Subanalysis
Clopidogrel Versus Ticagrelor or Prasugrel After Primary Percutaneous Coronary Intervention According to CYP2C19 Genotype A POPular Genetics Subanalysis
复制标题
DOI：
10.1161/circinterventions.120.009434
复制
发表时间：
2021-04-01
影响因子：
5.6
通讯作者：
ten Berg, Jurrien M.
中科院分区：
文献类型：
--
作者：
Claassens, Daniel M. F.;Bergmeijer, Thomas O.;ten Berg, Jurrien M.
背景：在心肌梗塞患者中，指南更倾向于替卡格雷或普拉格雷而不是氯吡格雷。然而，广受欢迎的遗传学试验(初次经皮冠状动脉介入治疗后的患者结局)显示，与常规的替卡格雷/普拉格雷治疗相比，在初次经皮冠状动脉介入治疗的患者中，以CYP2C19基因为导向的策略与出血风险降低有关，而不会增加血栓形成风险。然而，在特定的CYP2C19基因亚群中，最佳的P2Y(12)抑制剂治疗仍然是一个有争议的主题。方法：对Popular Genetics试验进行预先指定的子分析，使用的是确定了CYP2C19*2、*3和*17基因的患者。计划进行两种不同的分析。第一项研究评估了接受氯吡格雷治疗的患者中CYP2C19*17等位基因的影响。第二项研究比较了氯吡格雷在功能缺失等位基因非携带者和替卡格雷/普拉格雷治疗患者中的效果，而不考虑CYP2C19基因。主要结果是12个月后血栓形成的结果(心血管死亡、心肌梗死、支架血栓形成和中风)和出血的结果(柏拉图[血小板抑制和患者结果]大出血和轻微出血)。结果：共有2429名患者进入分析。在第一次分析中，未发现CYP2C19*17基因多态对血栓形成(调整风险比，0.95[95%可信区间，0.45-2.02])或出血结局(调整风险比，0.74[95%可信区间，0.48-1.18])有显著影响。在第二项分析中，与替卡格雷或普拉格雷相比，氯吡格雷的出血事件数较少(9.9%比11.7%，调整后风险比0.74[95%可信区间0.56-0.96])，血栓事件发生率没有显著增加(调整后风险比3.4%比2.5%，调整后风险比1.14[95%可信区间0.68-1.90])。结论：在没有携带CYP2C19功能缺失等位基因的原发性冠状动脉介入治疗患者中，使用氯吡格雷与替卡格雷或普拉格雷相比，出血率较低。而不会增加血栓事件。未发现CYP2C19*17基因多态对临床结果的影响。注册：网址：https://www.clinicaltrials.gov；唯一标识：NCT01761786。Https://www.trialregister.nl/；唯一标识：NL2872。GRAPHIC摘要：本文提供了一个图形摘要。
BACKGROUND: Guidelines favor ticagrelor or prasugrel over clopidogrel in patients with myocardial infarction. However, the POPular Genetics trial (Patient Outcome After Primary Percutaneous Coronary Intervention [PCI]) showed that in patients with primary PCI, a CYP2C19 genotype-guided strategy was associated with a lower bleeding risk without increasing thrombotic risk, compared with routine ticagrelor/prasugrel treatment. Nevertheless, optimal P2Y(12) inhibitor treatment in specific CYP2C19 genetic subgroups is still a subject of debate.METHODS: A prespecified subanalysis of the POPular Genetics trial was performed, using patients in whom CYP2C19*2, *3, and *17 genotypes was determined. Two different analyses were planned. The first assessed the effect of the CYP2C19*17 allele in clopidogrel-treated patients. The second compared the effect of clopidogrel in noncarriers of a loss-of-function allele with ticagrelor/prasugrel-treated patients, irrespective of CYP2C19 genotype. Main outcomes were a thrombotic outcome (cardiovascular death, myocardial infarction, stent thrombosis, and stroke) and a bleeding outcome (PLATO [Platelet Inhibition and Patient Outcomes] major and minor bleeding) after 12 months.RESULTS: A total of 2429 patients were used for analyses. In the first analysis, the CYP2C19*17 polymorphism was not found to have a significant influence on thrombotic (adjusted hazard ratio, 0.95 [95% CI, 0.45-2.02]) or bleeding outcomes (adjusted hazard ratio, 0.74 [95% CI, 0.48-1.18]). In the second analysis, clopidogrel was associated with a lower number of bleeding events compared with ticagrelor/prasugrel (9.9% versus 11.7%, adjusted hazard ratio, 0.74 [95% CI, 0.56-0.96]), without a significant increase in thrombotic events (3.4% versus 2.5%, adjusted hazard ratio, 1.14 [95% CI, 0.68-1.90]).CONCLUSIONS: In patients with primary PCI not carrying a CYP2C19 loss-of-function allele, the use of clopidogrel compared with ticagrelor or prasugrel was associated with lower bleeding rates, without an increase in thrombotic events. No effect on clinical outcomes was found for the CYP2C19*17 polymorphism.REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01761786. URL: https://www.trialregister.nl/; Unique identifier: NL2872.GRAPHIC ABSTRACT: A graphic abstract is available for this article.