Cardiothoracic and Vascular Department, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy.
Curr Vasc Pharmacol. 2021;19(5):542-555. doi: 10.2174/1570161118666200820141131.
Clopidogrel monotherapy is guideline-recommended in symptomatic peripheral artery disease (PAD). The advent of new antithrombotic strategies prompts an updated analysis of available evidence on antiplatelet therapy for PAD.
We searched MEDLINE, Embase and CENTRAL through January 2019 for randomised controlled trials and observational studies comparing antiplatelet therapies as monotherapy, dual therapy, or combination with anticoagulants. Efficacy (major adverse cardiovascular events, acute or chronic limb ischaemia, vascular amputation, peripheral revascularisation) and safety (all-cause mortality and overall bleeding) outcomes were evaluated via Bayesian network meta-analyses.
We analysed 26 randomised controlled trials. Clopidogrel (hazard ratio, HR, 0.78; 95% credible interval [CrI] 0.65-0.93) and ticagrelor (HR 0.80; 95% CrI 0.65-0.98) significantly reduced major adverse cardiovascular events risk compared with aspirin. No significant difference was observed for dual antiplatelet therapy with clopidogrel and aspirin. Vorapaxar significantly reduced limb ischaemia and revascularisation compared with placebo, while dual antiplatelet therapy with clopidogrel and aspirin showed a trend for reduced risk of amputation compared with aspirin (risk ratio 0.68; 95% CrI 0.43-1.04). For all-cause mortality, picotamide, vorapaxar, dipyridamole with aspirin, and ticlopidine showed a significantly lower risk of all-cause mortality vs aspirin. Clopidogrel and ticagrelor showed similar overall bleeding risk vs aspirin, while dual antiplatelet therapy with clopidogrel and aspirin significantly increased bleeding risk.
This updated network meta-analysis confirms that clopidogrel significantly decreases the risk of major adverse cardiovascular events compared with aspirin, without increasing bleeding risk. Clopidogrel should remain a mainstay of PAD treatment, at least in patients at higher bleeding risk.
氯吡格雷单药治疗是有症状外周动脉疾病（PAD）的指南推荐。新的抗血栓形成策略的出现促使人们对 PAD 的抗血小板治疗可用证据进行了更新分析。
我们通过搜索 MEDLINE、Embase 和 CENTRAL 数据库，检索了截至 2019 年 1 月的比较抗血小板治疗作为单药、双联治疗或与抗凝剂联合治疗的随机对照试验和观察性研究。通过贝叶斯网络荟萃分析评估了疗效（主要不良心血管事件、急性或慢性肢体缺血、血管截肢、外周血运重建）和安全性（全因死亡率和总出血）结局。
我们分析了 26 项随机对照试验。与阿司匹林相比，氯吡格雷（危险比，HR，0.78；95%可信区间[CrI] 0.65-0.93）和替格瑞洛（HR 0.80；95% CrI 0.65-0.98）显著降低了主要不良心血管事件的风险。氯吡格雷和阿司匹林双联抗血小板治疗无显著差异。与安慰剂相比，沃拉帕沙显著降低了肢体缺血和血运重建的风险，而氯吡格雷和阿司匹林双联抗血小板治疗与阿司匹林相比，截肢风险呈降低趋势（风险比 0.68；95% CrI 0.43-1.04）。对于全因死亡率，比卡酰胺、沃拉帕沙、双嘧达莫与阿司匹林、噻氯匹定与阿司匹林相比，全因死亡率的风险显著降低。氯吡格雷和替格瑞洛与阿司匹林的总体出血风险相似，而氯吡格雷和阿司匹林双联抗血小板治疗显著增加了出血风险。
本更新的网络荟萃分析证实，与阿司匹林相比，氯吡格雷可显著降低主要不良心血管事件的风险，且不会增加出血风险。氯吡格雷仍应成为 PAD 治疗的主要药物，至少在出血风险较高的患者中应如此。
