译 者：周娜 陕西省榆林市靖边县医院
校 审：赵鹏 郑州市第一人民医院
文献提供：柳宏伟 吉林大学中日联谊医院
CLINICAL CONTEXT
The antithrombotic effect duration of aspirin and clopidogrel is estimated to be 7 days5.The duration of action of a single dose of warfarin is estimated at 2 to 5 days5.Hence, to reverse the antithrombotic effect, it is generally recommended that AP agents be stopped 7 to 10 days, and warfarin 5 days, preprocedure6.Shorter discontinuation periods were used in many of the reviewed studies.
Stopping antithrombotics increases the risk of TE events. The exact magnitude of this risk increase is unknown. To minimize this risk, it seems reasonable to minimize the duration of antithrombotic discontinuation.
When considering the risks and benefits of antithrombotic discontinuation, it is important to consider both the frequency of undesirable outcomes and their long-term consequences. TE events occur infrequently, but the associated morbidity and mortality rates are high. In contrast, most reported bleeding outcomes are relatively mild. Decisions regarding periprocedural antithrombotic therapy depend on weighing these competing risks in the context of individual patient characteristics.
Patient preferences must inform these risk–benefit judgments. In a study comparing preferences of patients with atrial fibrillati on with those of physicians, patients were willing to experience a mean of 17.4 excess-bleeding events with warfarin and 14.7 excess-bleeding events with aspirin to prevent a stroke7. Sample clinical scenarios for guideline application are presented in appendix 1.
临床意义
阿司匹林联合氯吡格雷抗栓作用持续时间约为7天[5]。单用华法林药效持续时间约2-5天[5]。因此，围手术期间，为避免抗凝药物副作用，通常建议抗血小板聚集治疗需停用7-10天，华法林需停用5天[6]。部分研究建议的时间更短。
停用抗栓药物增加血栓栓塞风险，其风险的程度目前尚不清楚。为使风险降至最低，应适当缩短停用抗栓药物持续时间。
考虑到抗栓治疗的风险和获益，不良后果和长期预后的评估也是非常重要的。血栓栓塞疾病虽然并不常见，但其发病率和死亡率均较高。相比之下，很多有关出血结果的报道却相对较轻。围手术期的抗栓治疗决策依赖于权衡患者个体特点情况下风险与获益矛盾的比较。
此项治疗的风险和获益情况应当告知患者，一项对房颤患者差异性治疗研究表明，患者愿意接受华法林治疗而承担严重出血后果风险为17.4，使用阿司匹林预防卒中的出血风险为14.7[7]。用于临床工作的指导意见详见附录1。
RECOMMENDATIONS 建 议
1. It is axiomatic that clinicians managing antithrombotic medications periprocedurally weigh bleeding risks from drug continuation against TE risks from discontinuation at the individual patient level, although high-quality evidence on which to base this decision is often unavailable. In addition, even when evidence is insufficient to exclude a difference in bleeding or shows a small increase in clinically important bleeding with antithrombotic agents, physicians may reasonably judge that the risks and morbidity of TE events exceed those associated with bleeding.
2. Neurologists should counsel both patients taking aspirin for secondary stroke prevention and their physicians that aspirin discontinuation is probably associated with increased stroke and TIA risk (Level B). Estimated stroke risks vary across studies and according to duration of aspirin discontinuation.
3. Neurologists should counsel patients taking AC for stroke prevention that the TE risks associated with different AC periprocedural management strategies (continuing oral AC or stopping it with or without bridging heparin) are unknown (Level U) but that the risk of TE complications with warfarin discontinuation is probably higher if AC is stopped for $7 days (Level B).
4. Patients taking aspirin should be counseled that aspirin continuation is highly unlikely to increase clinically important bleeding complications with dental procedures (Level A). Given minimal clinically important bleeding risks, it is reasonable that stroke patients undergoing dental procedures should routinely continue aspirin (Level A).
1、目前研究共识认为制定围手术期抗栓药物治疗方案时，使用药物的出血风险和停药后血栓栓塞风险依据患者个体差异，尽管这一结论无可靠依据。另外，即使尚无有效证据排除出血的差异或表明抗凝治疗增加出血情况，临床医师可以合理判断血栓栓塞事件风险及患病率远高于与抗栓治疗相关的出血。
2、神经科医生应该建议患者服用阿司匹林作为脑卒中二级预防和听取临床医生建议，停用阿司匹林可能增加卒中和TIA风险（B级证据）。根据停用阿司匹林时间长短及相关研究评估卒中风险。
3、神经病学专家应该建议服用抗凝药物预防卒中患者，血栓栓塞风险是否与抗凝治疗策略（继续口服抗凝药物或停药后使用/过渡性肝素治疗）有关仍不清楚，但停用华法林导致的血栓栓塞并发症与停用抗凝药物≥7天显著相关（B级证据）。
4、服用阿司匹林的患者应被告知，服用阿司匹林不增加牙科手术时临床出血并发症（A级证据）。鉴于临床上出血风险较小，卒中患者接受牙科手术时应该继续服用阿司匹林是合理的（A级证据）。
5.Patients taking aspirin should be counseled that aspirin continuation probably does not increase clinically important bleeding complications with invasive ocular anesthesia, cataract surgery, dermatologic procedures, transrectal ultrasound–guided prostate biopsy, spinal/epidural procedures, and carpal tunnel surgery (Level B). Given minimal clinically important bleeding risks, it is reasonable that stroke patients undergoing these procedures should probably continue aspirin (Level B).
6. Aspirin continuation might not increase clinically important bleeding in vitreoretinal surgery, EMG, transbronchial lung biopsy,colonoscopic polypectomy, upper endoscopy with biopsy, sphincterotomy, and abdominal ultrasound-guided biopsies. Given the weaker data supporting minimal clinically important bleeding risks, it is reasonable that some stroke patients undergoing these procedures should possibly continue aspirin (Level C)
7. Although bleeding events were rare, studies of transurethral resection of the prostate lack the statistical precision to exclude clinically important bleeding risks with aspirin continuation (Level U).
8.Patients taking aspirin should be counseled that aspirin probably increases bleeding risks during orthopedic hip procedures (Level B).
5、服用阿司匹林的患者应该被告知，接受侵入性眼麻醉、白内障手术，皮肤手术，直肠超声引导的前列腺活检，脊髓/硬脊膜下操作术及腕管手术时，常规服用阿司匹林并不会增加临床上严重的出血并发症（B级证据）。鉴于临床上出血风险较小，卒中病人在进行以上手术时继续服用阿司匹林可能也是合理的。
6、在进行晶状体剥离术、肌电图、经支气管肺活检，结直肠息肉切除，上消化道内镜活检，括约肌切开术、经腹部超声引导穿刺术时，鉴于较少的数据支持临床出血风险，部分进行手术的卒中患者可继续服用阿司匹林是合理的。
7、尽管出血事件很少，但有关经尿道前列腺切除术尚缺乏可靠数据排除临床严重的出血风险和持续服用阿司匹林的关系（U级证据）。
8、服用阿司匹林的患者应该被告知在进行骨科髋部手术时阿司匹林可能增加出血风险（B级证据）。
9. Neurologists should counsel patients that there is insufficient evidence to make recommendations regarding appropriate periprocedural clopidogrel, ticlopidine, or aspirin/dipyridamole management in most situations (Level U).Aspirin recommendations cannot be extrapolated with certainty to other AP agents.
10. Patients taking warfarin should be counseled that warfarin continuation is highly unlikely to be associated with increased clinically important bleeding complications with dental procedures (Level A). Given minimal bleeding risks, stroke patients under-going dental procedures should routinely continue warfarin (Level A).
11. Patients taking warfarin should be counseled that warfarin continuation is probably associated with only a small (1.2%) increased risk difference for bleeding during dermatologic procedures on the basis of a meta-analysis of heterogeneous and conflicting studies (Level B). Thus, patients undergoing dermatologic procedures should probably continue warfarin (Level B).
12. Patients taking warfarin should be counseled that warfarin continuation is probably not associated with an increased risk of clinically important bleeding with ocular anesthesia (Level B). However, AC practices during ophthalmologic procedures may be driven by the postanesthesia procedure. Although bleeding events were rare, ophthalmologic studies (other than those regarding ocular anesthesia) lack the statistical precision to exclude clinically important bleeding risks with warfarin continuation. Thus, there is insufficient evidence to make practice recommendations regarding warfarin discontinuation in ophthalmologic procedures (Level U).
9、神经病学专家应该告知患者，在很多情况之下对于服用硫酸氢氯吡格雷、噻氯匹定、或阿司匹林/双嘧达莫的患者，目前尚无确切证据为围手术期的患者提供最佳的管理方案（U级证据）。有关阿司匹林的建议不能想当然的推广到其他抗血小板药物治疗策略中。
10、服用华法林的患者应该被告知，在进行牙科手术操作时，持续服用华法林不会导致临床严重的出血并发症（A级证据）。鉴于最小的出血风险，卒中患者进行牙科手术操作时，应该常规继续服用华法林（A级证据）。
11、服用华法林的患者应该被告知，依据多因素和相互冲突的meta分析结果得出，进行皮肤手术时持续服用华法林可能仅增加1.2%出血风险（B级证据）。因此，患者进行皮肤手术时应该常规继续使用华法林（B级证据）。
12、服用华法林的患者应该被告知，持续服用华法林患者接受眼部麻醉手术时，并不会增加临床重要的出血风险（B级证据）。然而，抗凝治疗可能作用于眼科术后的麻醉恢复过程。尽管出血事件很少，但眼科学研究（除了那些眼科麻醉）缺乏确切有效的统计学数据排除服用华法林引起的临床重要出血风险。因此，关于眼科手术时停用华法林，目前尚无有效证据作为标准推荐（U级证据）。
13. Warfarin might be associated with no increased clinically important bleeding with EMG, prostate procedures, inguinal herniorrhaphy, and endothermal ablation of the great saphenous vein. Thus, patients undergoing these procedures should possibly continue warfarin (Level C).
14. Patients taking warfarin should be counseled that warfarin continuation might increase bleeding with colonoscopic polypectomy (LevelC). Thus, patients undergoing this procedure should possibly temporarily discontinue warfarin (LevelC).
15. Neurologists should counsel patients that there is insufficient evidence to make recommendations regarding appropriate periprocedural management of nonwarfarin oral AC (Level U). Warfarin recommendations cannot be extrapolated with certainty to other AC agents.
16. There is insufficient evidence to determine differences in TE in chronically anticoagulated patients managed with heparin bridging therapy relative to oral AC discontinuation or continuation. Patients taking warfarin should be counseled that bridging therapy is probably associated with increased bleeding risks in procedures in general relative to AC cessation (Level B). Bridging probably does not reduce clinically important bleeding relative to continued AC with warfarin in dentistry, but bleeding risk differences between patients managed with continued warfarin vs bridging therapy in other procedures are unknown. Given that the benefits of bridging therapy are not established and that bridging is probably associated with increased bleeding risks, there is insufficient evidence to support or refute bridging therapy use in general (Level U).
13、华法林可能并不会增加以下操作的临床重要出血风险，如肌电图、前列腺手术、腹股沟疝修补术和大隐静脉消融术。因此，患者进行以上手术时应当尽量继续服用华法林（C级证据）
14、服用华法林患者应该被告知华法林治疗可能增加结肠镜下息肉切除术出血风险（C级推荐）。因此，患者进行上述手术时可能需要暂时停用华法林（C级证据）。
15、神经病学专家应该告知围手术期口服非华法林的其他抗凝药物患者，目前尚无可靠研究证据和管理措施推荐（U级推荐）。华法林的推荐建议并不能延伸运用于其他抗凝策略。
16、目前尚无明确证据表明，长期服用肝素抗凝治疗患者与终止/继续口服抗凝药物患者发生血栓栓塞的差异。服用华法林患者应该被告知，与停用抗凝药物相比，肝素过渡性治疗可能增加手术出血风险（B级证据）。牙科手术时，与口服华法林相比，过渡性治疗可能并不会降低临床重要出血风险。但在其他手术时，继续应用华法林与过渡性治疗的出血风险尚不清楚。鉴于过渡性治疗的获益并不确定，也可能增加出血风险，总的来说尚无确切证据支持或拒绝过渡性治疗（U级证据）。
Sample clinical scenarios for guideline application.
Clinical scenario 1: Patient A is a 65-year-old man with a history of hypertension and hypercholesterolemia who had a stroke 1 year ago attributed to intracranial large-artery atherosclerosis. He has mild residual left hemiparesis, and his secondary stroke prevention therapy includes risk factor control and aspirin 325 mg daily. He is due for routine colonoscopy screening. His neurologist reviews the guideline and assesses that the patient’s risk for recurrent stroke includes his known intracranial large-artery atherosclerotic event. Given that the patient may not need polypectomy with his colonoscopy, that the risk difference for bleeding with polypectomy associated with aspirin is approximately 2.0%, and that bleeding with polypectomy is likely to have lower morbidity risk than recurrent stroke risk, the neurologist recommends that aspirin be continued pericolonoscopy and obtains the opinions of both the patient and his gastrointestinal physician. The patient wants to have his colonoscopy, as his cousin was recently diagnosed with colon cancer, and is willing to accept an increased bleeding risk to avoid recurrent stroke. Thus, he proceeds with colonoscopy and possible polypectomy while continuing aspirin 325 mg daily.
临床指南病例示范
临床病例1:患者A男性，65岁，既往高血压、高胆固醇血症，1年前因颅内大动脉粥样硬化导致脑梗死，遗留左侧肢体轻偏瘫，脑卒中二级预防治疗包括危险因素控制和阿司匹林325mg/天。他准备进行常规的结肠镜检查。神经内科医生回顾指南评估患者当前再发卒中风险包括已知的颅内大动脉粥样硬化原因。建议考虑患者并不需要行肠镜下息肉切除术，在应用阿司匹林情况下，息肉切除术的出血风险约为2%，而且结肠息肉切除术出血风险可能比再发脑卒中的风险更低，神经内科医生建议结肠镜检查前可继续服用阿司匹林，患者本人和他的胃肠科医生同意此项建议。由于他表哥最近诊断患有结肠癌，患者想要进行结肠镜检查，为避免再发脑卒中，患者愿意接受增加的出血风险。因此，他进行了结肠镜检查和可能需要结肠息肉切除术，期间继续服用阿司匹林325mg/每天。
Clinical scenario 2: Patient B is a 70-year-old woman who had a small-vessel distribution ischemic stroke associated with uncontrolled hypertension 5 years previously. She has no residual deficits and has been diligent in controlling her vascular risk factors. She has recently been diagnosed with breast cancer requiring mastectomy. Her neurologist reviews the guideline and notes that there is minimal literature for the risks associated with more invasive procedures. The neurologist counsels the patient and her oncologist that the patient likely has a relatively low risk of recurrent stroke with brief aspirin cessation and that there is little research on bleeding risks with aspirin during invasive procedures. Together, they choose to stop the aspirin 7 days before the surgery and restart it the day after the surgery. The importance of restarting the aspirin postoperatively is stressed, and a specific start date is provided to the patient.
临床病例2:患者B，女性70岁，5年前因未控制高血压，导致小血管支配的缺血性卒中，并未遗留后遗症并且严格控制血管危险因素。最近确诊为乳腺癌需行乳腺切除术。神经内科医生回顾了指南为最大程度降低侵入性外科手术的风险。神经内科医生建议患者和肿瘤科医生短时间停用阿司匹林导致患者再发卒中的风险较低，而且有关侵入性手术期间使用阿司匹林导致出血风险的研究很少。结合以上情况，他们选择在手术前7天停用阿司匹林，术后第一天再次开始服用。术后重新启动阿司匹林治疗及提供给患者明确启动日期是及其重要的。
Clinical scenario 3: Patient C is a 60-year-old man with chronic atrial fibrillation and prior cardioembolic stroke treated with chronic warfarin. He is the primary caregiver for his wife with Alzheimer disease, but his cataracts have worsened to the degree that surgery is needed for him to continue to care for her and drive her to appointments. The patient’s neurologist reviews the guideline and finds that the risks associated with warfarin during ophthalmologic procedures have not been established with sufficient precision. The patient feels strongly, however, that he would rather tolerate the chance of increased bleeding complications than risk a recurrent cardioembolic stroke that might impair his ability to care for his wife. Given the risk–benefit ratio and patient preference, the ophthalmologist, neurologist, and patient decide to continue warfarin during the cataract surgery.
临床病例3: 患者C，男性60岁，慢性房颤病史，之前因心源性卒中接受长期华法林治疗，他是患有阿尔茨海默病妻子的主要照顾者，但是他的白内障已恶化，需要手术治疗才能继续照顾妻子和开车送她约会。患者的神经内科医师回顾指南后发现眼科手术期间服用华法林导致出血风险仍无确切证据。然而患者愿望强烈，宁可承担出血并发症，也不愿接受再发心源性卒中风险，从而导致影响照顾妻子的能力。鉴于风险获益率和患者的选择，眼科医生、神经内科医生和患者决定在行白内障手术期间继续服用华法林。
参考文献略
译 者：周娜 陕西省榆林市靖边县医院 ；校 审：赵鹏 郑州市第一人民医院；文献提供：柳宏伟 吉林大学中日联谊医院；编辑：李会琪；李神经群文献翻译中心出品
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