Tunehag Kayla R, Pearce Ashton F, Fox Layna P, Stouffer George A, Solander Sten, Lee Craig R
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Division of Cardiology, Department of Medicine, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Clin Transl Sci. 2025 Jan;18(1):e70131. doi: 10.1111/cts.70131.
In neurovascular settings, including treatment and prevention of ischemic stroke and prevention of thromboembolic complications after percutaneous neurointerventional procedures, dual antiplatelet therapy with a P2Y12 inhibitor and aspirin is the standard of care. Clopidogrel remains the most commonly prescribed P2Y12 inhibitor for neurovascular indications. However, patients carrying CYP2C19 no-function alleles have diminished capacity for inhibition of platelet reactivity due to reduced formation of clopidogrel's active metabolite. In patients with cardiovascular disease undergoing a percutaneous coronary intervention, CYP2C19 no-function allele carriers treated with clopidogrel experience a higher risk of major adverse cardiovascular outcomes, and multiple large prospective outcomes studies have shown an improvement in clinical outcomes when antiplatelet therapy selection was guided by CYP2C19 genotype. Similarly, accumulating evidence has associated CYP2C19 no-function alleles with poor clinical outcomes in clopidogrel-treated patients in neurovascular settings. However, the utility of implementing a genotype-guided antiplatelet therapy selection strategy in the setting of neurovascular disease and the clinical outcomes evidence in neurointerventional procedures remains unclear. In this review, we will (1) summarize existing evidence and guideline recommendations related to CYP2C19 genotype-guided antiplatelet therapy in the setting of neurovascular disease, (2) evaluate and synthesize the existing evidence on the relationship of clinical outcomes to CYP2C19 genotype and clopidogrel treatment in patients undergoing a percutaneous neurointerventional procedure, and (3) identify knowledge gaps and discuss future research directions.
在神经血管疾病领域,包括缺血性中风的治疗与预防以及经皮神经介入手术后血栓栓塞并发症的预防,使用P2Y12抑制剂和阿司匹林的双重抗血小板治疗是标准治疗方案。氯吡格雷仍是神经血管疾病适应症中最常用的P2Y12抑制剂。然而,携带CYP2C19无功能等位基因的患者,由于氯吡格雷活性代谢物生成减少,抑制血小板反应性的能力降低。在接受经皮冠状动脉介入治疗的心血管疾病患者中,接受氯吡格雷治疗的CYP2C19无功能等位基因携带者发生主要不良心血管事件的风险更高,多项大型前瞻性结局研究表明,根据CYP2C19基因型指导抗血小板治疗选择可改善临床结局。同样,越来越多的证据表明,在神经血管疾病领域,携带CYP2C19无功能等位基因与氯吡格雷治疗患者的不良临床结局相关。然而,在神经血管疾病背景下实施基于基因型的抗血小板治疗选择策略的效用以及神经介入手术中的临床结局证据仍不明确。在本综述中,我们将(1)总结与神经血管疾病背景下CYP2C19基因型指导的抗血小板治疗相关的现有证据和指南建议,(2)评估并综合现有证据,探讨经皮神经介入手术患者的临床结局与CYP2C19基因型及氯吡格雷治疗之间的关系,(3)找出知识空白并讨论未来的研究方向。