2021 ESC 主动脉和外周动脉疾病的抗栓治疗共识（三）

下肢动脉疾病

1和表2总结了对LEAD患者进行抗血栓治疗的试验。^{16,18,74–86}

信息要点

LEAD患者的抗血栓治疗

对于存在无症状下肢动脉疾病（LEAD）且其他区域没有明显冠状动脉疾病或PAD的患者使用阿司匹林，尚无经过验证的好处。伴随其他临床动脉粥样硬化疾病（如CAD）的无症状LEAD患者存在较高的心血管事件风险。在没有高出血风险情况下，在这种背景下可建议通过在阿司匹林基础上加用利伐沙班2.5mg bid强化抗血栓形成方法。

抗血小板治疗是有症状LEAD患者抗血栓形成策略的主要支柱。对于没有高出血风险的慢性有症状LEAD稳定型患者，建议在低剂量阿司匹林的基础加用利伐沙班2.5mg bid。^*

如果计划进行SAPT，则氯吡格雷可能优于阿司匹林。

长期DAPT治疗慢性有症状LEAD的优势尚未获得明确证据。

在阿司匹林基础上加用氯吡格雷不但未被证明对于移植物通畅存在有益影响，而且与血管手术后患者的出血风险增加存在相关性。

对于因LEAD进行血管重建（手术或血管内）且出血风险不高的患者，建议使用低剂量阿司匹林和利伐沙班2.5mg bid。^*

*颅内出血或缺血性卒中病史、或其他颅内病理史、近期胃肠道出血或可能因胃肠道失血引起的贫血、与出血风险增加相关的其他胃肠道病理、肝功能衰竭、出血性素质或凝血障碍，极高龄或脆弱，或eGFR<15mL/min/1.73m²的肾功能衰竭。

无症状下肢动脉疾病的长期抗血栓治疗

通过低踝臂指数确定的无症状LEAD存在较高的MACE和MALE风险。^78,87然而，两项试验未能证明在这种背景下长期服用阿司匹林的好处（表2）。^74,75COMPASS试验根据CAD入选的患者中，其中1422名患者也为无症状LEAD。⁸⁸在该组中，DPI对于MACE（HR 0.73；95% CI 0.45–1.18）和MALE（HR 0.74；95% CI 0.46–1.18）的有效结果与整体试验相似，不存在相互作用。尽管如此，该结果不能外推至无症状LEAD和没有相关临床动脉粥样硬化疾病的患者。

有症状LEAD的长期抗血栓治疗

抗血小板药物可以改善有症状LEAD的心血管预后（表2）。^{12，16，18，76，78，79，87}目前指南推荐低剂量阿司匹林或氯吡格雷。¹在CAPRIE研究中，氯吡格雷在降低临床LEAD患者的MACE方面相比阿司匹林具有优效性（HR 0.74；95% CI 0.64–0.91）。¹⁸招募13885名有症状LEAD患者的EUCLID试验发现替格瑞洛和氯吡格雷之间的MACE不存在差异。⁷⁹此外，两组之间的急性肢体缺血风险不存在差异。⁸⁹

关于DAPT，CHARISMA试验（表2）表明，服用阿司匹林 氯吡格雷与单用阿司匹林相比，3096名LEAD患者亚组中的MACE降低趋势并不显著。⁷⁶

在TRA2P-TIMI 50试验中，在阿司匹林和/或氯吡格雷基础上加用沃拉帕沙进行了测试。⁹⁰在20170名心肌梗死或有症状LEAD病史患者中，据报告MACE风险显著降低17%，两组之间不存在异质性（表2）。在LEAD患者中，发现使用沃拉帕沙的ALI和切断术显著减少，但代价是大出血和颅内出血显著过多（表2）。⁷⁸这种药物均未在欧洲市场上销售。

COMPASS试验报告在CAD和/或PAD完整研究总体（n=27395）⁸⁸以及有症状LEAD患者中使用利伐沙班2.5mg bid t阿司匹林可导致MACE和MALE显著减少。¹⁶这种合并用药导致大出血增加（但既非致命性也非颅内出血），但对于糖尿病、肾功能不全、心力衰竭或多血管疾病患者而言尤其利大于弊。^91,92

图1 包括>500名患者的下肢动脉疾病抗血栓治疗主要试验。黑色试验标题：仅包括下肢动脉疾病患者。红色试验标题：将存在下肢动脉疾病作为其中一项入选标准。

外科旁路手术后的抗血栓治疗

大约三分之一的下肢静脉移植物出现导管和/或吻合口病变，并对其通畅性造成威胁。静脉旁路血栓形成主要发生在第一年之内。⁹³较小口径导管、非隐静脉以及在腘窝下吻合时风险更大。尽管抗血小板药物常用，但没有有力证据表明哪种抗血栓策略能够最有效维持静脉移植物的通畅。^81–83CASPAR试验表明，与单用阿司匹林比较，阿司匹林 氯吡格雷在接受膝下旁路移植术的1年随访患者中没有优势（表2）。⁸³基于改善通畅性的微弱证据（BypassOral抗凝血剂或阿司匹林试验）（表2），可以考虑在出血风险较低但导管风险较高（如径流不良或重做程序）的患者中使用华法林。⁸²

腹股沟下假体移植物的长期通畅率低于静脉移植物。⁹³CASPAR试验的亚组分析表明，DAPT不会导致大出血显著增加，对于人工移植物闭塞、血管重建、切断术或死亡有益。⁸³VKA不能改善人工移植物的通畅性，但对于静脉导管略有益处。^82,94一项单中心回顾性研究表明，VKA可能与因径流不良的高风险假体移植物通畅时间延长存在相关性（表2）。⁹⁵

血管内手术后的抗血栓治疗

与血管内手术相关抗血栓药物治疗的选择、剂量和持续时间目前尚不明确。一项包括3529名患者的Cochrane荟萃分析对抗血栓药物预防再狭窄或再闭塞的作用进行了评估。⁹⁶与阿司匹林加安慰剂相比，阿司匹林加双嘧达莫并没有达到降低效果（OR 0.69；95% CI 0.44–1.10）。DAPT通常在血管内手术后使用，其持续时间通常在1到3个月之间，存在很大的变异性。⁹⁷有关PAD的ESC指南推荐在腹股沟下支架植入后使用DAPT（阿司匹林t氯吡格雷）至少1个月。¹腘窝下动脉支架植入术通常需要更长的DAPT持续时间，但没有可用证据。

DAPT持续时间主要基于冠状动脉支架置入术推断，但可能并不充分：在LEAD与CAD患者中发现对二磷酸腺苷和花生四烯酸存在更高的残留血小板活性。⁹⁸与经皮冠状血管介入治疗的患者相比，接受外周血管成形术的患者对阿司匹林和氯吡格雷的反应可能更弱。⁹⁸MIRROR试验将80名接受股腘血管内介入治疗的患者随机分为两组：阿司匹林与DAPT。⁸⁵在6个月时，DAPT组的靶病变血运重建（TLR）显著减少（表2）。此后患者仅接受阿司匹林治疗，TLR的初始差异在12个月时不再具有显著性。最近对接受血管内血管重建术的693名患者进行的一项回顾性分析表明，DAPT>_6个月是降低MACE（HR 0.61；95% CI 0.40–0.93）和MALE（HR 0.55；95% CI 0.38–0.77）风险的独立预测变量，并且不存在大出血的显著增加。⁹⁹在一项RCT中，与噻氯匹定加阿司匹林相比，西洛他唑加阿司匹林让3年血管通畅率获得改善（表2）。⁸⁴然而，西洛他唑目前在欧洲药品说明书中没有标识具有抗血栓形成特性。

阿司匹林；ACS，急性冠脉综合征；AT，抗血栓策略；APT，抗血小板治疗；C，氯吡格雷；CLTI，慢性危及肢体性缺血；CV，心血管；CVD，心源性死亡；DAPT，双联抗血栓治疗；Edox，依度沙班；EP，终点；EVT，血管内治疗；Fem-pop,股腘；HR，风险比；LEAD，下肢动脉疾病；MI，心肌梗塞；Mo，月；OAC，口服抗凝血剂；Pts，患者；R，利伐沙班；RCT，随机临床试验；Revasc，血管重建；SAPT，单一抗血小板治疗；Yrs，年

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