2021 ESC 主动脉和外周动脉疾病的抗栓治疗共识（四） / 四六文摘

外周血管重建后的双通路抑制

VOYAGER-PAD试验在6564例接受外科或血管内下肢血管重建患者中从血管重建后10天开始对DPI（利伐沙班2.5 mg bid t阿司匹林）对比阿司匹林的安全性和有效性进行了评估（表2）。⁸⁰根据研究者酌情决定额外使用氯吡格雷达到6个月。在28个月中位随访期间，DPI与阿司匹林相比，主要疗效终点（急性肢体缺血（ALI）、大截肢、心肌梗死（MI）、缺血性卒中或心源性死亡）率显著降低（15.5%与17.8%，P=0.009）。

就安全性而言，DPI组的2.65%以及阿司匹林组的1.87%发生TIMI大出血（P=0.07）。将结果应用到10000名患者的总体，DPI策略能够以每年29次TIMI大出血事件为代价预防181次主要疗效事件。两个试验组中大约50%的患者还接受了氯吡格雷治疗，主要是在血管内治疗后给药。DPI的有益作用与氯吡格雷无关（主要终点：使用氯吡格雷HR 0.85；95% CI 0.71–1.01对比不使用氯吡格雷HR 0.86；95% CI 0.73–1.01）。两种情况下的主要安全性结果不存在差异（使用氯吡格雷的HR1.32；95% CI 0.78–2.24，对比不使用氯吡格雷的HR 1.55；95% CI 0.88–2.73）。氯吡格雷给药超过1个月时，大出血（ISTH标准）风险较高，并且随时间增加。¹⁰⁰由于氯吡格雷的加用并未随机化，目前没有DPI和DAPT（阿司匹林t氯吡格雷）策略之间的头对头比较数据。后者已被凭经验用于血管内治疗，并根据专家意见进行了二次推荐，而前者已在VOYAGER试验中得到验证。⁸⁰

此外，COMPASS试验证实了DPI策略对MACE和MALE的益处，其可以在血管重建后不做任何变化地延长。¹⁶

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

肾动脉和肠系膜动脉

信息要点：肾和肠系膜动脉的抗血栓治疗

·SAPT适用于动脉粥样硬化肾或肠系膜动脉狭窄患者的心血管疾病预防。

·建议在肾或肠系膜动脉支架置入术后使用DAPT至少1个月。

有关肾动脉或肠系膜动脉粥样硬化疾病患者的抗血栓治疗数据非常少见，但考虑到任何动脉粥样硬化疾病患者均存在较高心血管风险，因此其使用存在合理性。¹⁰¹^–¹⁰⁵

·在发生可能与复杂主动脉斑块相关的栓塞事件后，可建议DAPT。

患有外周动脉疾病并伴有口服抗凝血剂适应症的患者

信息要点：PAD和存在其他需要抗凝治疗适应症患者的抗血栓形成策略。

·在将全剂量OAC用于慢性PAD患者的其他疾病时，由于存在出血风险，除非最近进行过经皮血管重建术，否则通常应避免加用抗血小板治疗。¹⁰⁶

·考虑到出血风险，可在高血栓形成风险的患者中使用SAPT和OAC。

PAD患者可能存在其他需要临时/永久抗凝治疗的情况。LEAD患者存在较高的AF风险，¹⁰⁷在超过10%因LEAD住院患者中观察到心律失常，并且与较高的卒中、截肢和死亡风险存在相关性。¹⁰⁸^,¹⁰⁹

根据定义，AF和PAD患者的CHA2DS2-VASc评分≥1，因此符合使用OAC的条件。在AF患者中将利伐沙班与华法林比较的ROCKET AF试验表明，LEAD患者的主要结果方面存在类似益处，利伐沙班与VKA相比出血率更高（HR 1.40；95% CI 1.06–1.86，相互作用P=0.037）。¹¹⁰

然而，在一项CAD或LEAD患者的回顾性研究中（HR 1.13；95% CI 0.84–1.52），¹¹¹利伐沙班与VKA在大出血方面不存在显著性差异，在ARISTOTLE试验的LEAD亚组（HR 1.05；95% CI 0.69–1.58）中的阿哌沙班与VKA也是如此。¹¹²在一项台湾全国性队列研究中，非VKA口服抗凝血剂（NOAC）与VKA相比，出血率较低（HR 0.64；95% CI 0.50–0.80），这可能与中国患者使用剂量较低有关。¹¹³由于缺乏针对AF和PAD患者的特异性试验，NOAC仍然优于VKA。¹¹⁴

对于存在PAD的AF患者，在OAC基础上加用抗血小板治疗（APT）没有可靠的理由。一项包括14199名AF、心力衰竭和共存CAD或PAD住院患者的研究表明，与单用VKA相比，在VKA基础上加用APT并不能减少缺血事件，反而会增加出血风险。¹⁰⁶在一项针对CAD伴随AF患者的RCT中，对伴随CAD的AF患者在OAC基础上加用APT并没有减少MACE，反而会增加出血。¹¹⁵因此，我们建议避免在需要全剂量OAC的PAD患者中常规加用APT。

有关外周支架置入术最佳抗血栓治疗方案的证据尚未发现。我们建议接受全剂量OAC的患者进行短期SAPT。这种合并用药的持续时间应尽可能受到限制（1个月），具体取决于临床适应症和出血风险；在出血风险较高的情况下，应使用获准用于预防卒中的最低NOAC剂量。¹¹⁴

最近一项针对四项RCT的荟萃分析对NOAC和氯吡格雷组合与VKA、阿司匹林和氯吡格雷三联疗法在接受冠状动脉支架置入术患者中的作用进行了对比，结果表明，双联治疗可减少34%的出血，但会让支架血栓形成风险增加59%。¹¹⁶

值得注意的是，主要和/或临床相关出血事件的频率是缺血事件的3倍以上。将该证据外推到PAD，在闭塞性支架血栓形成风险通常较低的情况下，我们建议使用aNOAC加氯吡格雷对接受外周动脉支架置入术的AF患者进行1个月治疗，仅在支架血栓形成风险最高（如，既往支架血栓形成、干预结束时重度血流缓慢）的特定病例加用1个月的阿司匹林（即三联疗法）。相反，如果出血风险很高，则应单独使用OAC。

PAD患者的出血风险

在开始抗血栓治疗之前，必须进行出血风险评估。与普通CAD患者相比，PAD患者通常具有更高的出血风险。¹¹⁷^,¹¹⁸但有关PAD患者出血风险的数据非常有限。这类患者的HASBLED等评分表明存在较差的预后表现。¹¹⁹

最近，学术研究联盟高出血风险（ARC-HBR）评分已被确认为接受经皮冠状血管介入治疗CAD患者的出血预测工具，¹²⁰但尚未在PAD患者中进行过评估。少量针对PAD患者提出的出血风险评分在表3中列出。¹¹⁸^,¹¹⁹^,¹²¹^–¹²³

仅有一项研究评估了质子泵抑制剂对减少PAD患者胃肠道出血的益处：COMPASS试验发现作为复合主要终点的上消化道事件并没有显著减少（HR 0.88；95% CI 0.67–1.15），但显示作为次要终点的泮托拉唑治疗胃肠道病变继发性出血出现显示减少（HR 0.52；95% CI 0.28–0.94）。¹²⁴

结论

过去几年进行的多项试验让对于PAD患者抗血栓治疗的认知取得实质性进展。基于疾病位置的图文摘要对优化策略进行了示意性总结。尽管如此，存在可疑缺血/出血风险比的复杂情况仍需在多学科团队中逐病例进行讨论，并考虑患者的偏好。由于个体患者的缺血和出血风险会随着时间推移发生变化，因此对抗血栓药物的选择进行定期重新评估仍然非常重要。

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2021 ESC 主动脉和外周动脉疾病的抗栓治疗共识（四）

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