2021 ESC 主動脈和外周動脈疾病的抗栓治療共識（三）

下肢動脈疾病

1和表2總結了對LEAD患者進行抗血栓治療的試驗。^{16,18,74–86}

信息要點

LEAD患者的抗血栓治療

對于存在無症狀下肢動脈疾病（LEAD）且其他區域沒有明顯冠狀動脈疾病或PAD的患者使用阿司匹林，尚無經過驗證的好處。伴随其他臨床動脈粥樣硬化疾病（如CAD）的無症狀LEAD患者存在較高的心血管事件風險。在沒有高出血風險情況下，在這種背景下可建議通過在阿司匹林基礎上加用利伐沙班2.5mg bid強化抗血栓形成方法。

抗血小闆治療是有症狀LEAD患者抗血栓形成策略的主要支柱。對于沒有高出血風險的慢性有症狀LEAD穩定型患者，建議在低劑量阿司匹林的基礎加用利伐沙班2.5mg bid。^*

如果計劃進行SAPT，則氯吡格雷可能優于阿司匹林。

長期DAPT治療慢性有症狀LEAD的優勢尚未獲得明确證據。

在阿司匹林基礎上加用氯吡格雷不但未被證明對于移植物通暢存在有益影響，而且與血管手術後患者的出血風險增加存在相關性。

對于因LEAD進行血管重建（手術或血管内）且出血風險不高的患者，建議使用低劑量阿司匹林和利伐沙班2.5mg bid。^*

*顱内出血或缺血性卒中病史、或其他顱内病理史、近期胃腸道出血或可能因胃腸道失血引起的貧血、與出血風險增加相關的其他胃腸道病理、肝功能衰竭、出血性素質或凝血障礙，極高齡或脆弱，或eGFR<15mL/min/1.73m²的腎功能衰竭。

無症狀下肢動脈疾病的長期抗血栓治療

通過低踝臂指數确定的無症狀LEAD存在較高的MACE和MALE風險。^78,87然而，兩項試驗未能證明在這種背景下長期服用阿司匹林的好處（表2）。^74,75COMPASS試驗根據CAD入選的患者中，其中1422名患者也為無症狀LEAD。⁸⁸在該組中，DPI對于MACE（HR 0.73；95% CI 0.45–1.18）和MALE（HR 0.74；95% CI 0.46–1.18）的有效結果與整體試驗相似，不存在相互作用。盡管如此，該結果不能外推至無症狀LEAD和沒有相關臨床動脈粥樣硬化疾病的患者。

有症狀LEAD的長期抗血栓治療

抗血小闆藥物可以改善有症狀LEAD的心血管預後（表2）。^{12，16，18，76，78，79，87}目前指南推薦低劑量阿司匹林或氯吡格雷。¹在CAPRIE研究中，氯吡格雷在降低臨床LEAD患者的MACE方面相比阿司匹林具有優效性（HR 0.74；95% CI 0.64–0.91）。¹⁸招募13885名有症狀LEAD患者的EUCLID試驗發現替格瑞洛和氯吡格雷之間的MACE不存在差異。⁷⁹此外，兩組之間的急性肢體缺血風險不存在差異。⁸⁹

關于DAPT，CHARISMA試驗（表2）表明，服用阿司匹林 氯吡格雷與單用阿司匹林相比，3096名LEAD患者亞組中的MACE降低趨勢并不顯著。⁷⁶

在TRA2P-TIMI 50試驗中，在阿司匹林和/或氯吡格雷基礎上加用沃拉帕沙進行了測試。⁹⁰在20170名心肌梗死或有症狀LEAD病史患者中，據報告MACE風險顯著降低17%，兩組之間不存在異質性（表2）。在LEAD患者中，發現使用沃拉帕沙的ALI和切斷術顯著減少，但代價是大出血和顱内出血顯著過多（表2）。⁷⁸這種藥物均未在歐洲市場上銷售。

COMPASS試驗報告在CAD和/或PAD完整研究總體（n=27395）⁸⁸以及有症狀LEAD患者中使用利伐沙班2.5mg bid t阿司匹林可導緻MACE和MALE顯著減少。¹⁶這種合并用藥導緻大出血增加（但既非緻命性也非顱内出血），但對于糖尿病、腎功能不全、心力衰竭或多血管疾病患者而言尤其利大于弊。^91,92

圖1 包括>500名患者的下肢動脈疾病抗血栓治療主要試驗。黑色試驗标題：僅包括下肢動脈疾病患者。紅色試驗标題：将存在下肢動脈疾病作為其中一項入選标準。

外科旁路手術後的抗血栓治療

大約三分之一的下肢靜脈移植物出現導管和/或吻合口病變，并對其通暢性造成威脅。靜脈旁路血栓形成主要發生在第一年之内。⁹³較小口徑導管、非隐靜脈以及在腘窩下吻合時風險更大。盡管抗血小闆藥物常用，但沒有有力證據表明哪種抗血栓策略能夠最有效維持靜脈移植物的通暢。^81–83CASPAR試驗表明，與單用阿司匹林比較，阿司匹林 氯吡格雷在接受膝下旁路移植術的1年随訪患者中沒有優勢（表2）。⁸³基于改善通暢性的微弱證據（BypassOral抗凝血劑或阿司匹林試驗）（表2），可以考慮在出血風險較低但導管風險較高（如徑流不良或重做程序）的患者中使用華法林。⁸²

腹股溝下假體移植物的長期通暢率低于靜脈移植物。⁹³CASPAR試驗的亞組分析表明，DAPT不會導緻大出血顯著增加，對于人工移植物閉塞、血管重建、切斷術或死亡有益。⁸³VKA不能改善人工移植物的通暢性，但對于靜脈導管略有益處。^82,94一項單中心回顧性研究表明，VKA可能與因徑流不良的高風險假體移植物通暢時間延長存在相關性（表2）。⁹⁵

血管内手術後的抗血栓治療

與血管内手術相關抗血栓藥物治療的選擇、劑量和持續時間目前尚不明确。一項包括3529名患者的Cochrane荟萃分析對抗血栓藥物預防再狹窄或再閉塞的作用進行了評估。⁹⁶與阿司匹林加安慰劑相比，阿司匹林加雙嘧達莫并沒有達到降低效果（OR 0.69；95% CI 0.44–1.10）。DAPT通常在血管内手術後使用，其持續時間通常在1到3個月之間，存在很大的變異性。⁹⁷有關PAD的ESC指南推薦在腹股溝下支架植入後使用DAPT（阿司匹林t氯吡格雷）至少1個月。¹腘窩下動脈支架植入術通常需要更長的DAPT持續時間，但沒有可用證據。

DAPT持續時間主要基于冠狀動脈支架置入術推斷，但可能并不充分：在LEAD與CAD患者中發現對二磷酸腺苷和花生四烯酸存在更高的殘留血小闆活性。⁹⁸與經皮冠狀血管介入治療的患者相比，接受外周血管成形術的患者對阿司匹林和氯吡格雷的反應可能更弱。⁹⁸MIRROR試驗将80名接受股腘血管内介入治療的患者随機分為兩組：阿司匹林與DAPT。⁸⁵在6個月時，DAPT組的靶病變血運重建（TLR）顯著減少（表2）。此後患者僅接受阿司匹林治療，TLR的初始差異在12個月時不再具有顯著性。最近對接受血管内血管重建術的693名患者進行的一項回顧性分析表明，DAPT>_6個月是降低MACE（HR 0.61；95% CI 0.40–0.93）和MALE（HR 0.55；95% CI 0.38–0.77）風險的獨立預測變量，并且不存在大出血的顯著增加。⁹⁹在一項RCT中，與噻氯匹定加阿司匹林相比，西洛他唑加阿司匹林讓3年血管通暢率獲得改善（表2）。⁸⁴然而，西洛他唑目前在歐洲藥品說明書中沒有标識具有抗血栓形成特性。

阿司匹林；ACS，急性冠脈綜合征；AT，抗血栓策略；APT，抗血小闆治療；C，氯吡格雷；CLTI，慢性危及肢體性缺血；CV，心血管；CVD，心源性死亡；DAPT，雙聯抗血栓治療；Edox，依度沙班；EP，終點；EVT，血管内治療；Fem-pop,股腘；HR，風險比；LEAD，下肢動脈疾病；MI，心肌梗塞；Mo，月；OAC，口服抗凝血劑；Pts，患者；R，利伐沙班；RCT，随機臨床試驗；Revasc，血管重建；SAPT，單一抗血小闆治療；Yrs，年

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