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抗血小板药物消化道损伤的预防和治疗中国专家共识(2012更新版) - 副本

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264·史堡内型苤查!Q!!生!旦筮丝鲞筮!塑£!迪』婴丛型:丛!丝!:y!!:!!:盟!:!.标准与讨论.抗血小板药物消化道损伤的预防和治疗中国专家共识(2012更新版)抗血小板药物消化道损伤的预防和治疗中国专家共识组大量临床研究已证实抗血小板治疗对血栓栓塞性疾病一级和二级预防的益处‘1。2J。目前小剂量阿司匹林(75~150mg/d)广泛用于冠状动脉粥样硬化性心脏病(冠心病)、脑血管疾病和外周动脉疾病的治疗”J,尤其对急性冠状动脉综合征(ACS)和植入药物洗脱支架(DES)的患者,双联抗血小板治疗[阿司匹林联合二磷酸腺苷(ADP)受体拮抗剂(如氯吡格雷)]更为重要。抗血小板药物是一柄“双刃剑”,阿司匹林通过抑制环氧化酶,一方面抑制血小板活化和血栓形成,另一方面损伤消化道黏膜,导致溃疡形成和出血,严重时可致患者死亡;其他抗血小板药物如氯吡格雷也能加重消化道损伤,联合用药时损伤更为严重。临床医生有必要综合评估长期抗血小板治疗的获益和风险。为此我刊2009年刊出了《抗血小板药物消化道损伤的预防和治疗中国专家共识》HJ。鉴于近年来相关领域又发表了大量研究,本共识组在深入讨论并吸收最新研究成果基础上,对共识进行了更新。本共识旨在告诫和敦促临床医生在抗血小板治疗同时注意预防消化道损伤,通过心脏科医生与消化科医生协作,防患于未然,使更多心脑血管疾病患者从抗血小板治疗中获益。本共识主要针对治疗心脑血管疾病常规使用的抗血小板药物(如阿司匹林和氯吡格雷),不包括其他非甾体消炎药(NSAIDs)。一、流行病学目前,美国约5000万患者服用阿司匹林,每年经皮冠状动脉介入治疗(PCI)后接受双联抗血小板治疗的患者120万;中国因PCI而需要双联抗血小板治疗的患者,2005年登记数量为10万∞J,2008年约为16万,2011年超过30万。国内尚无小剂量阿司匹林使用情况的大规模流行病学调查资料。阿司匹林导致的消化道不良反应包括从轻微消化不良到致命性消化性溃疡出血和穿孑L。研究表明,阿司匹林可使消化道损伤危险增加2~4倍∞o。14项安慰剂对照研究的荟萃分析显示,阿司匹林导致严重消化道出血的绝对危险为每年0.12%,并与剂量相关。7J。一级预防荟萃分析提示,阿司匹林使消化道出血的发生率增加1.37倍¨1。一项回顾性DOI:10.3760/cma.j.issn.0578—1426.2013.03.027通信作者:胡大一,北京大学人民医院心内科,100044,Emailheart@public.fhnet.Ctl.net;林三仁,北京大学第三医院消化科100191.Email:linsanren@medmail.corn.crl万方数据mg/d)与阿司匹林(100mg/d)导致消化道出血的危险相似,相对危险度分别为2.7和2.8[9I。几项临床研究‘”。21均证实,当阿司匹林与14703例双联抗血小板治疗患者[心肌梗死后、左心功能不风险,但同时带来出血风险增加。13。“J。本节要点:抗血栓药物广泛应用于心脑血管疾病防治,即使小剂量阿司匹林也可能增加消化道损伤危险,氯吡格雷可加重消化道损伤,阿司匹林与氯吡格雷联合应用时危险性更高。二、阿司匹林和氯吡格雷致消化道损伤的机制‘15。”J(一)阿司匹林1.局部作用:阿司匹林对消化道黏膜有直接刺激作用,可直接作用于胃黏膜的磷脂层,破坏胃黏膜的疏水保护屏障;在胃内崩解使白三烯等细胞毒性物质释放增多,进而刺2.全身作用:阿司匹林可使环氧化酶(COX)活性中心的丝氨酸乙酰化,抑制胃黏膜的COX-1和COX-2活性,导致的功能。PG生成减少是阿司匹林引起胃肠道黏膜损伤的主(二)ADP受体拮抗剂该类药物通过阻断血小板膜上的ADP受体发挥抗血小化道黏膜,但可抑制血小板衍生的生长因子和血小板释放的血管内皮生长因子,从而阻碍新生血管生成和影响溃疡愈合。ADP受体拮抗剂可加重已存在的胃肠道黏膜损伤,包括阿司匹林、NSAIDs以及幽门螺杆菌(Hp)感染导致的消化道损伤‘…。本节要点:阿司匹林导致消化道损伤的机制包括局部作用和全身作用,而ADP受体拮抗剂可阻碍已受损消化道黏膜的愈合。三、抗血小板药物所致的消化道损伤的临床表现及特点(一)临床表现阿司匹林的不良反应以消化系统为主,其中以上消化道损伤更常见。2“。近年发现,接受双联抗血小板治疗并且多病例对照研究提示,氯吡格雷(75氯吡格雷联合应用时,消化道出血发生率明显高于单用1种抗血小板药物,其风险增加2—3倍。在VALIANT研究中,全和(或)心力衰竭]随访6个月时,上消化道出血发生率为0.37%。新型ADP受体拮抗剂,如普拉格雷和替格瑞洛与氯吡格雷比较的大规模研究提示可进一步降低心血管事件激并损伤胃黏膜;也可损伤肠黏膜屏障。前列腺素(PG)生成减少。PG主要胃肠道血流和黏膜要原因。板作用。与阿司匹林不同,ADP受体拮抗剂并不直接损伤消生堡囱型盘查生!旦箜!!鲞箜!塑垦!i!』婴丛四:塑!!些:!!!:!!:盥!:!·265·数联合应用PPI的患者,下消化道出血的发生率明显高于上消化道出血‘2…。1.常见症状:恶心、呕吐、上腹不适或疼痛、腹泻、呕血、黑便等。2“。2.常见病变:消化道黏膜糜烂、溃疡、威胁生命的消化道出血及穿孔,以及较少见的肠狭窄等。”J。阿司匹林所致溃疡的临床特点包括。”’2”:用药史,老年女性多见,多为无痛性,胃溃疡较十二指肠溃疡更多见,易发生出血及穿孔。(二)抗血小板药物与消化道损伤1.发生时间:服药后12个月内为消化道损伤的多发阶段,3个月时达高峰’9’”1。2.与剂量的关系:在一定范围内阿司匹林的抗血栓作用并不随剂量增加而增加,但消化道损伤风险却随剂量加大而明显增加一3“。荟萃分析显示‘32。,服用阿司匹林剂量>200mg/d的患者与<100mg/d的患者比较总出血事件发生率增加了3倍。因此,建议长期使用阿司匹林时应选择最低有效剂量(75~100mg/d)。3.与剂型的关系’3…:从机制上看,阿司匹林肠溶片较非肠溶片对胃黏膜的直接损伤作用小,但目前尚无泡腾片或肠溶片较平片明显降低阿司匹林消化道损伤危险的临床证据。”]。4.与年龄的关系’3“:老年患者是抗血小板药物消化道损伤的高危人群,年龄越大,危险越大‘”1,低剂量阿司匹林相关的上消化道出血风险随年龄增长而增加(年龄每增加1岁,消化道出血发生率增加2.3%)[36j。使用小剂量阿司匹林(75mg/d)的患者消化性溃疡穿孔的发生率:年龄≤65岁者为0.1‰;年龄>65岁者为1.07%0。”。。而抗血小板药物治疗又以老年人居多,且疗效肯定,在使用时应权衡利弊。5.与Hp感染的关系:Hp感染可加重阿司匹林的消化道损伤作用。”。3…。使用阿司匹林的Hp阳性者发生十二指肠溃疡的0R值为18.5,发生胃溃疡的0R值为2.3。6o,根除Hp可降低有溃疡出血病史患者溃疡复发的风险…1。因此,在开始长期抗血小板治疗之前,建议有条件的患者应检测并根除Hp。6.联合用药:抗血小板药物联合应用或抗血小板药物与抗凝药物联合使用会使上消化道出血的风险增加2~7倍。4“。ACS患者往往需联合使用多种抗血小板和(或)抗凝药物,此时尤其应注意消化道损伤风险的评估与预防。本节要点:阿司匹林所致消化道损伤的初期症状易被忽视,故一旦出血危险较高,对于有用药史的患者,不应忽视任何症状及体征变化。阿司匹林导致的消化道损伤风险随患者年龄和药物剂量增加而明显增加,合并Hp感染和联合用药也增加其危险性。四、长期抗血小板药物治疗患者消化道损伤的筛查与预防为了最大程度地减少抗血小板治疗的消化道损伤,建议临床医生采用标准化的流程进行风险评估和筛查(图1)。万方数据Hp:幽门螺杆菌;PPI:质子泵抑制剂;H2RA:H2受体拮抗剂图1减少抗血小板治疗患者消化道损伤的处理流程1.规范抗血小板治疗的适应证:抗血小板药物在减少司匹林。例如,欧洲指南建议下列患者不应使用阿司匹林作为一级预防用药。4…:既无心血管病,也无肾功能不全或心血在心血管病二级预防中,应合理控制抗血栓药物联合应2.识别消化道损伤的高危人群:抗血小板药物治疗研究亚组分析显示,65岁以上人群较之65岁以下人群从抗血小板治疗中获益更多,但高龄也是消化道损伤的危险因素。对于65岁以上的老年人,尤其在应用双联抗血小板治mg/d。既往有消化道疾病史的患者出现消化道损伤的危险性明显增加,发生过消化性溃疡出血的患者其危险增加13倍Ⅲ1,如继续服用阿司匹林,1年内复发率约为15%[453。使用抗血小板药物易发生消化道损伤的人群包括:65岁以上的老年人;有消化道出血、溃疡病史㈣1;有消化不良或有胃食管反流症状;双联抗血小板治疗的患者;合用华法林等抗凝药物的患者;合用NSAIDs或糖皮质激素的患者;此外,还包括Hp感染’6一“、吸烟、饮酒等‘4“…。3.合理联合应用抗血栓药物:阿司匹林与其他抗血小板或抗凝药物联合应用明显增加严重出血发生的危险,主要以消化道出血为主。因此,对于消化道损伤的高危人群应该避免联合抗血栓治疗,如需进行PCI应尽量选择裸金属支架,血栓事件的同时发生出血不良反应难以完全避免,故只有获益大于出血风险时才推荐使用。阿司匹林在心血管疾病二级预防的获益远超过风险,即阿司匹林减少心血管病死亡事件明显多于严重出血事件。但是,对于阿司匹林在心血管病一级预防中的地位还存在争议。目前,国内外指南一致建议应该根据患者的心血管病危险分层,选择中高危患者给予阿管病高危因素的高血压患者;不伴动脉粥样硬化性疾病的糖尿病患者。建议参考“中国心血管病预防指南”L4列选择有适应证的患者给予阿司匹林进行一级预防。用的时间以降低出血风险,尽量减少抗血栓药物的长期联合应用,包括不同抗血小板药物以及抗血小板与抗凝药物的联合。疗时,建议长期使用阿司匹林的剂量不要超过100·266·虫堡凼型盘查!Q!!生!旦筮!!鲞筮!塑堡!也』翌丛旦:丛型!:y!!:墼:盟!:!以减少双联抗血小板治疗的时间。抗凝治疗(华法林或肝素)不会直接导致消化道损伤,但会加重消化道出血的风险。长期联合应用口服抗凝药物华法林及抗血小板药物时,应将药物剂量调整至最低有效剂量,即阿司匹林为75—100mg/d,氯吡格雷为75mg/d,华法林剂量将国际标准化比值(INR)目标值定在2.0~2.5,但对于机械瓣膜置换术后的患者可能需要更高强度的抗凝治疗。随着新型药物洗脱支架的出现,未来有望减少双联抗血小板治疗的时间。4.筛查与根除Hp:对于长期服用小剂量阿司匹林的患者,Hp感染是消化道出血的危险因素㈣J,根除Hp可降低溃疡和出血的复发。目前推荐的筛查方法为¨C或14c呼气试验、粪便Hp抗原检测。检测前需停用抗菌药物及铋剂至少4周,停用PPI至少7d。建议在长期抗血小板治疗前检测Hp,阳性者应根除。5.应用H:受体拮抗剂(H:RA)预防消化道损伤:H:RA预防抗血小板药物相关消化道损伤的研究¨”1。表明,对服用阿司匹林(75~325mg/d)的患者,法莫替丁可预防胃十二指肠溃疡和糜烂性食管炎的发生"“。H:RA的疗效优于安慰剂,但比PPI差,其优点是费用较低,对不能使用PPI的患者可考虑应用∞2。J。法莫替丁与氯吡格雷之间无药物相互作用,且同时有保护胃黏膜的作用¨“。应避免使用西咪替丁,因其为CYP2C19强效抑制剂,可影响氯吡格雷的活化。6.应用PPI预防消化道损伤:内镜和流行病学研究均发现,PPI明显降低服用阿司匹林和(或)氯吡格雷患者所致消化道损伤的发生率∞”“。在随机对照临床试验中,PPI可使双联抗血小板治疗患者消化道出血减少87%¨“。PPI是预防抗血小板药物相关消化道损伤的首选药物,优于米索前列醇等黏膜保护剂和H:RA【5…。建议根据患者具体情况,决定PPI联合应用的时间,高危患者可在抗血小板药物治疗的前6个月联合使用PPI,6个月后改为H:RA或间断服用PPI。目前对于下消化道出血尚无有效预防措施,应注意监测患者症状、粪便潜血以及血常规,有报道米索前列醇对于阿司匹林引起的小肠黏膜损伤有效”“,但尚需大样本量临床本节要点:(1)为减少抗血小板药物的消化道损伤,应规范使用抗血栓药物,并按流程对高危患者进行评估和筛查;(2)严格掌握长期联合应用抗血栓药物的适应证,并调整至最低有效剂量;(3)建议对长期服用抗血小板药物的患者筛查并根除Hp,对高危患者同时给予有效抑酸药物,首选PPI,不能耐受PPI者,可给予H,RA。五、PPI与氯吡格雷的联合应用近期,关于氯吡格雷与PPI的药物相互作用引起广泛关注。氯吡格雷是前体药,口服后需在肝脏转化为有活性的代活性。氯吡格雷在肝脏通过两个步骤转化,主要涉及和CYP2C19抑制剂可影响氯吡格雷的抗血小板作用。而万方数据CYP2C19也是多数PPI在肝脏的代谢酶,某些PPI可抑制CYP2C19通路而影响氯吡格雷的活化,其程度取决于PPI的代谢途径及其与CYP2C19的亲和力。研究发现5种PPI对CYP2C19均具有竞争性抑制作用,其中泮托拉唑和雷贝拉唑的抑制作用最低。59。。尽管药理学上某些PPI与氯吡格雷存在相互作用,但PPI对氯吡格雷抗血小板作用的影响和心血管事件终点试验的临床研究结果并不一致。(一)PPI对氯吡格雷抗血小板作用的影响PPI干扰氯吡格雷抗血栓作用的证据主要来自药代动力学的体外研究和血小板活性的检测。以血小板聚集力为替代终点的随机对照研究显示,奥美拉唑使氯吡格雷抑制血小板聚集的作用减弱㈣”o,推测与奥美拉唑主要通过CYP2C19代谢,同时又是CYP2C19的强效抑制剂有关。在健康志愿者中进行的不同PPI对氯吡格雷稳态药代动力学和药效学影响的随机研究表明,与单用氯吡格雷相比,联合不同PPI均影响氯吡格雷的抗血小板聚集作用,其中奥美拉唑的抑制作用最强惭J。冠状动脉支架植入后服用氯吡格雷150mg/d的患者联合使用奥美拉唑或泮托拉唑1个月,泮托拉唑组较奥美拉唑组对氯吡格雷抗血小板作用影响小,奥美拉唑组44%患者为氯吡格雷无反应者,而泮托拉唑组仅为23%[61]。(二)PPI对服用氯吡格雷患者心血管事件的影响现有的临床研究尚不能证实联合PPI增加服用氯吡格雷患者的心血管事件或总体死亡率;但有证据表明联合PPI可显著降低消化性溃疡的复发率,尤其降低上消化道出血的发生率。1.氯吡格雷联用PPI增加心血管事件风险的证据:纳入13项研究共48674例患者的荟萃分析结果显示,PPI与心血管病事件发生和死亡危险增加相关,但是仅限于高危患者。6“。在BASKET研究中,PCI术后氯吡格雷和PPI联合应用的患者3年后心肌梗死发生率升高1倍,校正后,联合应用PPI仍然为的预后因素。6…。2.氯吡格雷联用PPI不增加心血管事件风险的证据:COGENT研究"川是目前评价PPI在双联抗血小板治疗的冠心病患者获益和风险的惟一大规模前瞻性随机安慰剂对照研究。尽管该研究提前终止,但是对人选的3761例患者的分析显示,预防性使用奥美拉唑使6个月时的消化道事件减少66%,而两组的心血管事件没有明显差异。但PPI对接受双联抗血小板治疗患者心血管事件的影响还需更大规模随机对照研究进一步提供证据。3.PPI作为心血管事件危险因素的证据:PLATO洛组,PPI组终点事件发生率均高于无PPI组(氯吡格雷+PPI组,HR=1.29;替格瑞洛+PPI组,HR=1.30),提示PPI以外的其他抗血小板药物治疗时,联合PPI也可增加心血管研究证实。谢产物后,才能与血小板膜P2Y12受体结合,而抑制血小板CYP2C19,其次为CYP3A4。研究证实CYP2C19基因多态性研究唧1的回顾性分析提示,无论是氯吡格雷组还是替格瑞是ACS患者发生心血管事件的危险因素。Kwok等070j对23项研究的荟萃分析显示,并没有证据表明不同PPI与氯吡格雷合用,其心血管事件的危险不同;使用除氯吡格雷虫堡凼挝苤查!Q!!至!旦筮!!鲞筮!塑堡堕!』翌丛塑:丛塑!!Q!!:!!!:!!:№:!事件风险(OR=1.28),提示PPI为心血管事件的危险因素。综上所述,尽管PPI与氯吡格雷在药代动力学上存在相互作用,并且体外血小板功能研究证实PPI减弱氯吡格雷的抗血小板作用。但是,目前并没有大规模临床研究证实PPI增加服用氯吡格雷的心血管病患者心血管病事件和死亡率。2009年至今,美国FDA与欧盟相继警示氯吡格雷不要与奥美拉唑(及埃索美拉唑)联合应用,但是不包括其他PPI。临床实践中,是否预防性使用PPI以减少抗血小板药物的消化道损伤,临床医师应根据患者的个体特点、用药时间等评估。对于消化道出血高危患者仍需联合PPI,但应充分考虑不同PPI对氯吡格雷抗血小板作用的影响,建议避免使用对CYP2C19抑制作用强的PPI,如奥美拉唑和埃索美拉唑。本节要点:(1)药理学上,不同PPI与氯吡格雷的相互作用存在差异;(2)氯吡格雷联合PPI可显著减少消化道不良反应,临床研究并未发现心血管病事件上的显著差异,但实验室研究表明某些PPI可影响氯吡格雷的抗血小板作用;(3)在抗血小板药物治疗的同时如需联合PPI,应尽量避免使用奥关拉唑或埃索美拉唑。六、抗血小板药物消化道损伤的处理1.停用抗血小板药物:发生消化道损伤时是否停用抗血小板药物,需根据消化道损伤的危险和心血管病的危险个体化评价。如果患者仅表现为消化不良症状,可不停用抗血小板药物而给予抑酸药;如患者发生活动性出血,常需停用抗血小板药物直到出血情况稳定。但某些患者因停用抗血小板药物会增加血栓事件风险,尤其是ACS、植入裸金属支架1个月内、药物涂层支架6个月内的患者,建议尽量避免完全停用抗血小板药物。患者联合使用多种抗血小板和抗凝药物时,如果发生出血,应考虑减少药物种类和剂量。当严重消化道出血威胁生命时,可能需要停用所有的抗凝和抗血小板药物,停药3~5d后,如出血情况稳定,可重新开始使用阿司匹林或氯吡格雷,尤其是心血管病高危风险的患者‘71。2|。阿司匹林导致的消化道出血在经过PPI治疗和(或)内镜下止血后,在严密监测下至少观察24h,如没有发生再出血,可重新开始抗血小板治疗,但需与PPI联合用药,同时密切监测患者出血复发的可能’7“。2.关于替代治疗:美国心脏病学学会(ACC)指南下调了因消化道损伤不能耐受阿司匹林的冠心病患者可以采用氯吡格雷替代的证据等级。这主要是由于该推荐的证据主要来自氯吡格雷及阿司匹林治疗缺血性事件危险患者的临床研究(CAPRIE)‘2’”1,尽管结果显示使用氯吡格雷的患者比使用阿司匹林的患者因消化道出血住院的发生率低(0.7%比1.1%),但研究中使用的阿司匹林剂量为325mg/d,而非目前临床常用的阿司匹林75~150mg/d。此外,随机对照研究证实,阿司匹林所致消化性溃疡患者在溃疡愈合后联合给予阿司匹林和PPI,溃疡复发及出血的发生率均较单用氯吡格雷替代治疗明显降低’7。”J。因此,对于溃疡出血复发危万方数据险较高的患者,不建议用氯吡格雷替代阿司匹林,而应该给予阿司匹林和PPI联合治疗"“。目前没有证据显示其他抗血小板药物能够安全、有效替代阿司匹林,尤其是作为心血管病一级预防。3.消化道损伤的治疗:应选择PPI、H:RA和黏膜保护剂一7-78],其中PPI是预防和治疗阿司匹林相关消化道损伤的首选药物。急性消化道出血总的治疗原则是"…:多学科合作共同商讨,平衡获益和风险以决定是否停用抗血小板药物;大剂量静脉应用PPI;必要时输血或内镜下止血。急性、严重出血的患者需暂时停用抗血小板药物,并严格掌握输血适应证,对血液动力学稳定、血细胞比容>25%或Hb>80∥L的患者可暂不输血。经过积极治疗严重出血仍然不能控制,必要时可输血小板。4.Hp根除治疗:所有需长期服用抗血小板药物的患者建议检测并根除Hp。目前推荐PPI、克拉霉素、阿莫西林加铋剂的四联疗法,疗程10—14d娜J。其他可选方案包括三联疗法、序贯疗法及个体化治疗等。本节要点:(1)发生消化道损伤后是否停用抗血小板药物需权衡患者的血栓和出血风险;(2)对于阿司匹林导致的消化道溃疡、出血患者,不建议氯吡格雷替代阿司匹林,建议阿司匹林联合PPI;(3)发生溃疡、出血的患者,应积极给予抑酸药和胃黏膜保护剂,首选PPI,并根除Hp,必要时输血。七、抗血小板治疗患者的内镜治疗使用抗血小板药物的患者进行内镜下活检或治疗时,首先应明确适应证,其次应评价患者心血管病风险及内镜操作出血的风险。心血管病低危而出血风险较高的患者应至少停用抗血小板药5d;心血管病高危(如药物洗脱支架植入后1年内)且出血风险也较高的患者,可进行内镜检查,但要尽量避免取活检或内镜治疗;心血管病高危而出血风险较低的患者可不停用抗血小板药物。所有患者均要全面评估内镜治疗的获益和风险。对于必须行内镜治疗的患者,应在内镜治疗充分止血后确认没有出血时再结束内镜检查,并密切监测,以便早期发现再出血。同时注意在内镜检查或治疗前准备好血小板,供必要时术中输注。本节要点:评估心血管疾病及消化道出血的风险,权衡利弊,进行内镜下检查或治疗。八、长期随访在长期治疗中,除了严格掌握抗血小板药物适应证并使用正确剂量外,临床医生和患者均需注意监测和观察消化道不适和出血等不良反应,尤其在用药最初12个月内,重点是有高危因素的患者。需要注意有无黑便或不明原因贫血,以早期发现不良反应。简单、经济而又有效的方法是对所有长期接受抗血小板药物治疗的患者进行指导,监测粪便颜色,及时发现柏油样便,每1—3个月定期检查粪便潜血及血常规。若出现异常及时诊治。本节要点:对于长期应用抗血小板药物的患者,临床医·268·虫堡凼型盘查!鱼!!至!旦箜!!鲞笠!塑£!也』坐丛型:丛!堡!!Q!!:y!!:!!:堕!:!生和患者均需注意监测消化道损伤的发生,注意有无黑便,定期行便潜血及血常规检查。总结1.阿司匹林是心脑血管疾病患者长期抗血栓治疗的基石,包括一级预防和二级预防。阿司匹林导致的致命性消化道损伤的比例很低,平均每5000例接受阿司匹林治疗的患者中出现1例呕血,而阿司匹林每治疗1000例患者每年减少19例严重心脑血管事件。8“。因此,对于有适应证的患者应坚持长期抗血小板治疗,同时采取适当措施避免和减少消化道损伤发生。同时,对消化道损伤高风险的人群注意评估是否有必要服阿司匹林进行一级预防。2.阿司匹林长期使用的最佳剂量为75~100mg/d,小剂量阿司匹林也可导致消化道损伤,不同剂型阿司匹林引起消化性溃疡及消化道出血的危险无明显差异。3.ADP受体拮抗剂(如氯吡格雷)可加重消化道损伤。4.消化道出血的高危人群:I>65岁、消化道溃疡或出血病史、合并Hp感染、联合抗血小板治疗或抗凝治疗、联合使用NSAIDs、糖皮质激素类药物治疗的患者。5.对于长期服用抗血小板药物的高危人群应筛查并根除Hp,可联合应用PPI或H,RA进行防治,首选PPI。6.发生消化道损伤后是否停用抗血小板药物需平衡患者的血栓和出血风险。出血稳定后尽早恢复抗血小板治疗。7.对于阿司匹林所致的溃疡、出血患者,不建议氯吡格雷替代阿司匹林治疗,推荐阿司匹林联合PPI治疗。8.服用氯吡格雷的患者需联合使用PPI时,尽量避免使用奥美拉唑及埃索美拉唑。9.双联抗血小板治疗时,如需合用PPI,建议连续使用不超过6个月,此后可换用H:RA或间断使用PPI。10.临床医生和患者均需注意监测长期服用抗血小板药物治疗时的消化道损伤,注意有无黑便,定期行粪便潜血及血常规检查。共识组成员(按姓氏汉语拼音排序):陈步星(北京天坛医院心内科);陈曼湖(中山大学附属第一医院消化科);房静远(上海交通大学医学院附属仁济医院消化科);郝建宇(首都医科大学附属北京朝阳医院消化科);胡大一(北京大学人民医院心内科);林三仁(北京大学第三医院消化科);刘梅林(北京大学第一医院老年病内科);刘玉兰(北京大学人民医院消化科);钱家鸣(中国医学科学院北京协和医学院北京协和医院消化科);沙卫红(广东省人民医院消化科);孙忠实(海军总医院药剂科);万征(天津医科大学总医院心内科);王邦茂(天津医科大学总医院消化科);吴学思(首都医科大学附属北京安贞医院心内科);严晓伟(中国医学科学院北京协和医学院北京协和医院心内科);杨云生(总医院消化科);张抒扬(中国医学科学院北京协和医学院北京协和医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作者:作者单位:刊名:英文刊名:年,卷(期):

抗血小板药物消化道损伤的预防和治疗中国专家共识组

中华内科杂志

Chinese Journal of Internal Medicine2013,52(3)

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