缺血与出血之间的博弈,高出血风险冠脉支架术后的抗血小板治疗

2022-07-30 心希望快迅 网络

对于特殊冠脉支架人群的个体化精准抗血小板治疗是临床工作中的难点和突破点,采用恰当的手段和方式识别高危出血人群,制定个体化的抗血小板治疗方案,从而不良事件发生率及改善临床预后。

 

阿司匹林联合P2Y12受体抑制剂的双联抗血小板治疗(DAPT)是经皮冠状动脉介入治疗(PCI)术后患者预防支架内血栓及全身动脉粥样硬化血栓事件的标准治疗方案。然而,临床中高出血风险(HBR)的冠脉支架植入患者也不少见,抗栓强度增强的同时势必会增加出血风险,故权衡缺血和出血的利弊是优化抗血小板治疗方案的重中之重。故本文将对HBR患者的抗血小板治疗进行介绍,以期为临床医生和患者提供帮助。

 

01

HBR的定义

 

高出血风险学术研究联合会于2019年发布了定义PCI患者高出血风险的共识文件,提出接受PCI的患者判断为HBR的11条主要标准和6条次要标准,其中符合1条主要标准或至少2条次要标准者定义为HBR-PCI患者[1]

 

主要标准

1)长期使用口服抗凝药;

2) 严重或终末期慢性肾病(估算的肾小球滤过率(eGFR)<30ml/min);

3) 血红蛋白<110g/L;

4) 6个月内发生过需要住院或输血治疗的自发性出血,或任意时间的复发出血;

5) 中重度基线血小板减少(血小板计数<100×109/L);

6) 慢性出血倾向;

7) 肝硬化伴门脉高压;

8) 12个月内诊断和/或需要治疗的恶性肿瘤(除外非黑色素瘤皮肤癌);

9) 既往自发性颅内出血(任何时间);

10)12个月内的创伤性颅内出血;

11) 脑血管畸形;

12) 6个月内的中重度缺血性卒中;

13) 接受DAPT期间不能延期的大手术;

PCI术前30天内进行过大手术或遭受大的创伤; 

 

 

 

次要标准

1) 年龄≥75岁;

2) 中度慢性肾病(eGFR 30-59ml/min);

3) 男性血红蛋白110-129g/L,女性血红蛋白110-119g/L;

4) 过去12个月内需要住院或输血的自发性出血,但未达到主要标准;

5) 长期使用非甾体抗炎药或类固醇;

6) 任何时间发生的缺血性卒中,未达到主要标准。

 

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02

HBR-PCI患者抗血小板治疗推荐

 

①P2Y12抑制剂的选择

P2Y12抑制剂包括氯吡格雷和替格瑞洛。一般情况下HBR患者选择出血风险较低的氯吡格雷或低剂量替格瑞洛治疗是合理的。但是,由于HBR患者多合并其他缺血高危因素,如糖尿病、冠脉复杂病变、对氯吡格雷或阿司匹林治疗抵抗等,甚至一些HBR标准本身也是高缺血风险的标准,如高龄、贫血、肾功能不全、既往卒中病史等,因此,只有在充分权衡缺血和出血风险、评估缺血和出血事件危害的基础上作出的选择才是合理的。

②缩短DAPT疗程

新一代药物洗脱支架(DES)在支架平台、涂层材料/方式、药物等方面均较第一代DES有了很大的提高,其支架内血栓风险和晚期追赶现象显著减少,为实现短DAPT提供了坚实的基础。既往研究证实[2-3],将HBR患者PCI术后的DAPT疗程缩短至1个月,仍可获得比金属裸支架(BMS)更好的疗效。但是,由于这些研究并没有对不同DAPT疗程进行对比,因此很难说明1个月的DAPT与更长的DAPT(如3个月、6个月等)相比,是否可以获得相同的抗缺血效果或更大的临床净获益。

③点单联抗血小板选择

以往由DAPT向单联抗血小板治疗(SAPT)转换时均建议停用P2Y12抑制剂而保留阿司匹林。但近年来研究者将目光聚焦于早期停用阿司匹林而保留P2Y12抑制剂单药治疗的新策略。由于胃肠道出血占DAPT过程中全部出血的近一半,而阿司匹林是导致胃肠出血的“罪魁祸首”,因此,停用阿司匹林而保留P2Y12抑制剂可望在保持抗栓疗效的基础上减少出血风险。对于HBR合并缺血高危因素的“双高危”患者,这种早期P2Y12抑制剂单药治疗策略与阿司匹林单药治疗相比,又可保留较多的抗栓作用,在理论上是更为合理的治疗策略。

 

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03

特殊类型HBR-PCI患者的

抗血小板治疗推荐[4-5]

 

(1)年龄≥75岁高龄患者:既是HBR也是高缺血风险的“双高危”人群。建议在阿司匹林基础上选择氯吡格雷作为首选的P2Y12抑制剂。

(2)合并肾功能不全患者:典型的“双高危”人群之一,但一般而言出血风险大于缺血风险。eGFR在30-60ml/min时,替格瑞洛的起效时间快于氯吡格雷且抗血小板作用更强,建议缺血风险高于出血风险时首选替格瑞洛,反之则首选氯吡格雷。eGFR<30ml/min时,替格瑞洛的肾性不良事件发生率显著增高,应首选氯吡格雷。

(3)需接受口服抗凝药(OAC)治疗的非瓣膜性房颤患者:需接受OAC治疗者,PCI围术期可给予DAPT,出院后即停用阿司匹林,如缺血风险较高,可考虑持续DAPT至1个月,但很少超过1个月。出血风险较高者可于6个月停用所有抗血小板药,否则于1年时停用,不建议OAC与替格瑞洛联合应用。

(4)合并血小板计数降低的患者:血小板计数低于100×109/L且大于60×109/L,低出血风险患者可首选氯吡格雷联合阿司匹林治疗,高出血风险患者可考虑使用单药(氯吡格雷或阿 司匹林)治疗,避免使用替格瑞洛;血小板计数低于60×109/L,且大于30×109/L,建议使用单药(氯吡格雷或阿司匹林)维持治疗,避免使用替格瑞洛;血小板计数低于30×109/L,建议停用所有抗血小板药物,并避免行PCI。

(5)近期拟接受外科大手术的患者:新一代DES术后接受至少1个月的DAPT即可,术前根据出血风险和心血管事件风险评估是否需要停用抗血小板药物。围术期需中断抗血小板药物者,术前3-5天停用替格瑞洛,术前5-7天停用氯毗格雷,术后24小时即可恢复使用。

 

 

对于特殊冠脉支架人群的个体化精准抗血小板治疗是临床工作中的难点和突破点,采用恰当的手段和方式识别高危出血人群,制定个体化的抗血小板治疗方案,从而不良事件发生率及改善临床预后。

 

 

 

参考文献:

[1]   TaUrban P, Mehran R, Colleran R,et al. Defining High Bleeding Risk in Patients Undergoing Percutaneous Coronary Intervention. Circulation. 2019 Jul 16;140(3):240-261.

[2]   Ariotti S, Adamo M, Costa F, et al. Is Bare-Metal Stent Implantation Still Justifiable in High Bleeding Risk Patients Undergoing Percutaneous Coronary Intervention?: A Pre-Specified Analysis From the ZEUS Trial. JACC Cardiovasc Interv.2016;9(5):426-436.

[3]   Varenne O, Cook S, Sideris G, Kedev S, et al. Drug-eluting stents in elderly patients with coronary artery disease (SENIOR): a randomised single-blind trial. Lancet. 2018 Jan 6;391(10115):41-50.

[4]   中华医学会心血管病学分会, 中华心血管病杂志编辑委员会. 冠心病合并心房颤动患者抗栓管理中国专家共识[J]. 中华心血管病杂志, 2020, 48(07):552-564.

[5]   中国医师协会心血管内科医师分会血栓防治专业委员会, 中华医学会心血管病学分会介入心脏病学组, 中华心血管病杂志编辑委员会. 急性冠状动脉综合征特殊人群抗血小板治疗中国专家建议[J]. 中华心血管病杂志, 2018(4):255-266.

 

 

 

 

 

 

 

 

 

 

 

 

 

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    2023-05-01 qindq
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    2023-05-22 gujh
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