Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, PO Box 100496, Gainesville, FL, USA.
Eur J Clin Pharmacol. 2022 Aug;78(8):1217-1225. doi: 10.1007/s00228-022-03346-7. Epub 2022 Jun 3.
To conduct a systematic review to identify studies that assessed the association between CYP2C19 polymorphisms and clinical outcomes in peripheral artery disease (PAD) patients who took clopidogrel.
We systematically searched Ovid EMBASE, PubMed, and Web of Science from November 1997 (inception) to September 2020. We included observational studies evaluating how CYP2C19 polymorphism is associated with clopidogrel's effectiveness and safety among patients with PAD. We extracted relevant information details from eligible studies (e.g., study type, patient population, study outcomes). We used the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) Tool to assess the risk of bias for included observational studies.
The outcomes of interest were the effectiveness and safety of clopidogrel. The effectiveness outcomes included clinical ineffectiveness (e.g., restenosis). The safety outcomes included bleeding and death related to the use of clopidogrel. We identified four observational studies with a sample size ranging from 50 to 278. Outcomes and comparison groups of the studies varied. Three studies (75%) had an overall low risk of bias. All included studies demonstrated that carrying CYP2C19 loss of function (LOF) alleles was significantly associated with reduced clinical effectiveness and safety of clopidogrel.
Our systematic review showed an association between CYP2C19 LOF alleles and reduced functions of clopidogrel. The use of CYP2C19 testing in PAD patients prescribed clopidogrel may help improve the clinical outcomes. However, based on the limited evidence, there is a need for randomized clinical trials in PAD patients to test both the effectiveness and safety outcomes of clopidogrel.
系统评价以明确评估 CYP2C19 多态性与服用氯吡格雷的外周动脉疾病（PAD）患者临床结局之间相关性的研究。
我们系统性检索了 Ovid EMBASE、PubMed 和 Web of Science，检索时间从 1997 年 11 月（创刊）至 2020 年 9 月。我们纳入了评估 CYP2C19 多态性与 PAD 患者氯吡格雷疗效和安全性之间相关性的观察性研究。我们从合格研究中提取了相关信息详情（例如，研究类型、患者人群、研究结局）。我们使用非随机干预研究的偏倚风险（ROBINS-I）工具评估纳入的观察性研究的偏倚风险。
我们关注的结局是氯吡格雷的疗效和安全性。疗效结局包括临床无效（如再狭窄）。安全性结局包括与氯吡格雷使用相关的出血和死亡。我们共确定了 4 项研究，样本量范围为 50 至 278 例。研究的结局和比较组各不相同。3 项研究（75%）整体偏倚风险较低。所有纳入的研究均表明，携带 CYP2C19 失活（LOF）等位基因与氯吡格雷的临床疗效和安全性降低显著相关。
我们的系统评价显示 CYP2C19 LOF 等位基因与氯吡格雷功能降低之间存在关联。在开具氯吡格雷处方的 PAD 患者中使用 CYP2C19 检测可能有助于改善临床结局。然而，基于有限的证据，需要在 PAD 患者中开展随机临床试验，以检验氯吡格雷的疗效和安全性结局。
