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譯 者：周娜 陜西省榆林市靖邊縣醫(yī)院 校 審：趙鵬 鄭州市第一人民醫(yī)院 文獻提供：柳宏偉 吉林大學中日聯(lián)誼醫(yī)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.
臨床意義 阿司匹林聯(lián)合氯吡格雷抗栓作用持續(xù)時間約為7天[5]。單用華法林藥效持續(xù)時間約2-5天[5]。因此，圍手術期間，為避免抗凝藥物副作用，通常建議抗血小板聚集治療需停用7-10天，華法林需停用5天[6]。部分研究建議的時間更短。
停用抗栓藥物增加血栓栓塞風險，其風險的程度目前尚不清楚。為使風險降至最低，應適當縮短停用抗栓藥物持續(xù)時間。
考慮到抗栓治療的風險和獲益，不良后果和長期預后的評估也是非常重要的。血栓栓塞疾病雖然并不常見，但其發(fā)病率和死亡率均較高。相比之下，很多有關出血結果的報道卻相對較輕。圍手術期的抗栓治療決策依賴于權衡患者個體特點情況下風險與獲益矛盾的比較。
此項治療的風險和獲益情況應當告知患者，一項對房顫患者差異性治療研究表明，患者愿意接受華法林治療而承擔嚴重出血后果風險為17.4，使用阿司匹林預防卒中的出血風險為14.7[7]。用于臨床工作的指導意見詳見附錄1。 RECOMMENDATIONS 建 議
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、目前研究共識認為制定圍手術期抗栓藥物治療方案時，使用藥物的出血風險和停藥后血栓栓塞風險依據(jù)患者個體差異，盡管這一結論無可靠依據(jù)。另外，即使尚無有效證據(jù)排除出血的差異或表明抗凝治療增加出血情況，臨床醫(yī)師可以合理判斷血栓栓塞事件風險及患病率遠高于與抗栓治療相關的出血。
2、神經(jīng)科醫(yī)生應該建議患者服用阿司匹林作為腦卒中二級預防和聽取臨床醫(yī)生建議，停用阿司匹林可能增加卒中和TIA風險（B級證據(jù)）。根據(jù)停用阿司匹林時間長短及相關研究評估卒中風險。
3、神經(jīng)病學專家應該建議服用抗凝藥物預防卒中患者，血栓栓塞風險是否與抗凝治療策略（繼續(xù)口服抗凝藥物或停藥后使用/過渡性肝素治療）有關仍不清楚，但停用華法林導致的血栓栓塞并發(fā)癥與停用抗凝藥物≥7天顯著相關（B級證據(jù)）。 4、服用阿司匹林的患者應被告知，服用阿司匹林不增加牙科手術時臨床出血并發(fā)癥（A級證據(jù)）。鑒于臨床上出血風險較小，卒中患者接受牙科手術時應該繼續(xù)服用阿司匹林是合理的（A級證據(jù)）。 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應該被告知，接受侵入性眼麻醉、白內(nèi)障手術，皮膚手術，直腸超聲引導的前列腺活檢，脊髓/硬脊膜下操作術及腕管手術時，常規(guī)服用阿司匹林并不會增加臨床上嚴重的出血并發(fā)癥（B級證據(jù)）。鑒于臨床上出血風險較小，卒中病人在進行以上手術時繼續(xù)服用阿司匹林可能也是合理的。
6、在進行晶狀體剝離術、肌電圖、經(jīng)支氣管肺活檢，結直腸息肉切除，上消化道內(nèi)鏡活檢，括約肌切開術、經(jīng)腹部超聲引導穿刺術時，鑒于較少的數(shù)據(jù)支持臨床出血風險，部分進行手術的卒中患者可繼續(xù)服用阿司匹林是合理的。
7、盡管出血事件很少，但有關經(jīng)尿道前列腺切除術尚缺乏可靠數(shù)據(jù)排除臨床嚴重的出血風險和持續(xù)服用阿司匹林的關系（U級證據(jù)）。
8、服用阿司匹林的患者應該被告知在進行骨科髖部手術時阿司匹林可能增加出血風險（B級證據(jù)）。 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、神經(jīng)病學專家應該告知患者，在很多情況之下對于服用硫酸氫氯吡格雷、噻氯匹定、或阿司匹林/雙嘧達莫的患者，目前尚無確切證據(jù)為圍手術期的患者提供最佳的管理方案（U級證據(jù)）。有關阿司匹林的建議不能想當然的推廣到其他抗血小板藥物治療策略中。
10、服用華法林的患者應該被告知，在進行牙科手術操作時，持續(xù)服用華法林不會導致臨床嚴重的出血并發(fā)癥（A級證據(jù)）。鑒于最小的出血風險，卒中患者進行牙科手術操作時，應該常規(guī)繼續(xù)服用華法林（A級證據(jù)）。
11、服用華法林的患者應該被告知，依據(jù)多因素和相互沖突的meta分析結果得出，進行皮膚手術時持續(xù)服用華法林可能僅增加1.2%出血風險（B級證據(jù)）。因此，患者進行皮膚手術時應該常規(guī)繼續(xù)使用華法林（B級證據(jù)）。
12、服用華法林的患者應該被告知，持續(xù)服用華法林患者接受眼部麻醉手術時，并不會增加臨床重要的出血風險（B級證據(jù)）。然而，抗凝治療可能作用于眼科術后的麻醉恢復過程。盡管出血事件很少，但眼科學研究（除了那些眼科麻醉）缺乏確切有效的統(tǒng)計學數(shù)據(jù)排除服用華法林引起的臨床重要出血風險。因此，關于眼科手術時停用華法林，目前尚無有效證據(jù)作為標準推薦（U級證據(jù)）。  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、華法林可能并不會增加以下操作的臨床重要出血風險，如肌電圖、前列腺手術、腹股溝疝修補術和大隱靜脈消融術。因此，患者進行以上手術時應當盡量繼續(xù)服用華法林（C級證據(jù)）
14、服用華法林患者應該被告知華法林治療可能增加結腸鏡下息肉切除術出血風險（C級推薦）。因此，患者進行上述手術時可能需要暫時停用華法林（C級證據(jù)）。
15、神經(jīng)病學專家應該告知圍手術期口服非華法林的其他抗凝藥物患者，目前尚無可靠研究證據(jù)和管理措施推薦（U級推薦）。華法林的推薦建議并不能延伸運用于其他抗凝策略。
16、目前尚無明確證據(jù)表明，長期服用肝素抗凝治療患者與終止/繼續(xù)口服抗凝藥物患者發(fā)生血栓栓塞的差異。服用華法林患者應該被告知，與停用抗凝藥物相比，肝素過渡性治療可能增加手術出血風險（B級證據(jù)）。牙科手術時，與口服華法林相比，過渡性治療可能并不會降低臨床重要出血風險。但在其他手術時，繼續(xù)應用華法林與過渡性治療的出血風險尚不清楚。鑒于過渡性治療的獲益并不確定，也可能增加出血風險，總的來說尚無確切證據(jù)支持或拒絕過渡性治療（U級證據(jù)）。 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.
臨床指南病例示范
臨床病例1:患者A男性，65歲，既往高血壓、高膽固醇血癥，1年前因顱內(nèi)大動脈粥樣硬化導致腦梗死，遺留左側肢體輕偏癱，腦卒中二級預防治療包括危險因素控制和阿司匹林325mg/天。他準備進行常規(guī)的結腸鏡檢查。神經(jīng)內(nèi)科醫(yī)生回顧指南評估患者當前再發(fā)卒中風險包括已知的顱內(nèi)大動脈粥樣硬化原因。建議考慮患者并不需要行腸鏡下息肉切除術，在應用阿司匹林情況下，息肉切除術的出血風險約為2%，而且結腸息肉切除術出血風險可能比再發(fā)腦卒中的風險更低，神經(jīng)內(nèi)科醫(yī)生建議結腸鏡檢查前可繼續(xù)服用阿司匹林，患者本人和他的胃腸科醫(yī)生同意此項建議。由于他表哥最近診斷患有結腸癌，患者想要進行結腸鏡檢查，為避免再發(fā)腦卒中，患者愿意接受增加的出血風險。因此，他進行了結腸鏡檢查和可能需要結腸息肉切除術，期間繼續(xù)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.
臨床病例2:患者B，女性70歲，5年前因未控制高血壓，導致小血管支配的缺血性卒中，并未遺留后遺癥并且嚴格控制血管危險因素。最近確診為乳腺癌需行乳腺切除術。神經(jīng)內(nèi)科醫(yī)生回顧了指南為最大程度降低侵入性外科手術的風險。神經(jīng)內(nèi)科醫(yī)生建議患者和腫瘤科醫(yī)生短時間停用阿司匹林導致患者再發(fā)卒中的風險較低，而且有關侵入性手術期間使用阿司匹林導致出血風險的研究很少。結合以上情況，他們選擇在手術前7天停用阿司匹林，術后第一天再次開始服用。術后重新啟動阿司匹林治療及提供給患者明確啟動日期是及其重要的。 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.
臨床病例3: 患者C，男性60歲，慢性房顫病史，之前因心源性卒中接受長期華法林治療，他是患有阿爾茨海默病妻子的主要照顧者，但是他的白內(nèi)障已惡化，需要手術治療才能繼續(xù)照顧妻子和開車送她約會?；颊叩纳窠?jīng)內(nèi)科醫(yī)師回顧指南后發(fā)現(xiàn)眼科手術期間服用華法林導致出血風險仍無確切證據(jù)。然而患者愿望強烈，寧可承擔出血并發(fā)癥，也不愿接受再發(fā)心源性卒中風險，從而導致影響照顧妻子的能力。鑒于風險獲益率和患者的選擇，眼科醫(yī)生、神經(jīng)內(nèi)科醫(yī)生和患者決定在行白內(nèi)障手術期間繼續(xù)服用華法林。 參考文獻略  譯 者：周娜 陜西省榆林市靖邊縣醫(yī)院 ；校 審：趙鵬 鄭州市第一人民醫(yī)院；文獻提供：柳宏偉 吉林大學中日聯(lián)誼醫(yī)院；編輯：李會琪；李神經(jīng)群文獻翻譯中心出品 |
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來自： 雨林醫(yī)風 > 《李神經(jīng)群臨床推理系列》
