老年上消化道出血与服用小剂量阿司匹林的关系

阿司匹林是非甾体类抗炎药物,具有较强的抗炎、抗血栓、镇痛等药理作用,小剂量阿司匹林常用于缺血性心脑血管疾病一级、二级的预防〔1,2〕。但是阿司匹林的胃肠道反应不容忽视,消化道出血及溃疡等不良反应的发生已经为临床医师所关注〔3,4〕。本文旨在探讨老年上消化道出血与服用小剂量阿司匹林的关系。     

阿司匹林致上消化道出血的临床分析

目的:探讨阿司匹林治疗心脑血管疾病所致上消化道出血的临床因素。方法:采取回顾性方法分析19 200人次服用常规剂量阿司匹林发生上消化道出血的相关因素。结果:服用常规剂量的阿司匹林发生上消化道出血与治疗的原发病无关,与阿司匹林用量、消化道病史、胃粘膜保护剂应用有关。结论:阿司匹林致上消化道出血与阿司匹林用量、消化道病史有关,应用胃粘膜保护剂可预防有消化道病史者的消化道出血。     

肠溶阿司匹林治疗冠心病的临床疗效及其诱发上消化道出血的相关因素分析

目的研究肠溶阿司匹林治疗冠心病的临床效果及其诱发上消化道出血的相关因素。方法选取我院86例冠心病患者作为研究对象,均给予肠溶阿司匹林治疗,治疗3个月后分析临床效果,统计用药期间上消化道出血发生情况,将发生上消化道出血者纳入出血组,将未发生上消化道出血纳入者未出血组,比较两组一般资料(性别、年龄、肠溶阿司匹林用药剂量、胃黏膜保护剂、消化道病史、酗酒史、吸烟史)。结果肠溶阿司匹林治疗后患者平均心肌缺血、心绞痛、心肌缺氧发作时间均短于治疗前(P0.05);本组86例冠心病患者,肠溶阿司匹林治疗发生上消化道出血32例,未发生上消化道出血54例;经Logistic多因素回归分析可知,年龄≥70岁、大剂量、有消化道病史、有酗酒史、有吸烟史、未使用胃黏膜保护剂是肠溶阿司匹林治疗冠心病诱发上消化道出血的独立危险因素(P0.05)。结论采用肠溶阿司匹林治疗冠心病的临床效果良好,但诱发上消化道出血的危险因素较多,临床应结合患者具情况加强上消化道出血的防治,提倡小剂量用药、配合使用胃黏膜保护剂,以提高患者用药安全性,减少患者痛苦。     

雷贝拉唑预防心血管病患者阿司匹林引起的消化性溃疡

目的 探讨雷贝拉唑对小剂量阿司匹林引起消化性溃疡的预防作用.方法 纳入2010年6月~2012年2月,患心血管病需抗血小板治疗的患者166例,随机分为对照组（n=83）和观察组（n=83）.对照组单用阿司匹林（100 mg,qd）;观察组在服用等剂量阿司匹林肠溶片同时服用雷贝拉唑钠肠溶胶囊（20 mg,qd）.对比两组患者出现上腹不适、上腹痛、烧心、反酸等消化道不适症状,同时比较两组胃镜下黏膜表现变化和呕血、黑便等消化道出血临床症状.结果 对照组和观察组分别出现消化道症状37例（44.6%）和4例（4.8%）,对照组胃肠黏膜损伤患者29例（34.9%）,其中消化性溃疡12例（14.5%）,观察组发生胃黏膜损伤患者仅6例（7.2%）,其中消化性溃疡1例（1.2%）,观察组的消化道症状发生率、胃肠粘膜损伤率以及消化性溃疡发生率均显著低于对照组,差异均有统计学意义（P均＜0.05）.随访3个月和6个月时患者呕血、黑便等消化道出血情况观察组均小于对照组,差异有统计学意义（P＜0.05）.结论 雷贝拉唑钠肠溶可降低小剂量阿司匹林治疗中发生溃疡出血的风险.     

Analysis on clinical manifestation and nroenostic factors of gastrointestinal bleeding with aspirin in 220 patients

目的 探讨服用阿司匹林抗血小板凝集患者消化道出血的发病率和相关危险因素,了解患者短期及长期的预后.方法 将220例服用阿司匹林抗血小板凝集患者分为出血组(21例)和对照组(199例),比较两组患者的年龄、性别、临床特点、近期及远期预后,采用多因素Logistic回归分析消化道出血的危险因素.结果 220例患者消化道出血的发病率为9.5％.消化道出血史是消化道再出血的独立危险因素(P＜0.01),而服用他汀类药物是消化道出血的保护因素(95％可信区间:0.13 ～0.50,P＜0.01).出血组和对照组患者30天死亡率分别是8.3％和0％,1年死亡率分别是20.8％和0％(P＜0.01).结论 消化道出血史是服用阿司匹林患者消化道再出血的独立危险因素,他汀类药物是其保护因素.与对照组比较,出血组患者的短期及长期死亡率均明显升高.有消化道出血史的患者采用抗血小板疗法时应综合考虑.     

阿司匹林治疗冠心病患者合并上消化道出血的影响因素

目的研究老年冠心病患者合并上消化出血应用阿司匹林治疗的影响因素分析.方法选取2015-11/2016-11在湖北省汉川市人民医院采用阿司匹林口服治疗的老年冠心病患者纳入214例进行回顾性分析,对发生上消化道出血51例患者的年龄、性别、服药时间、剂量、消化道病史、胃黏膜保护剂使用情况和吸烟史等进行分析.结果患者年龄随着时间逐渐增长,上消化道出血发生率明显增高(χ~2=11.526,P0.01);服药时间低于3 mo的患者上消化道出血率显著低于服药超过3 mo的患者,差异具有统计学意义(χ~2=8.530,P0.01);小剂量组患者上消化道出血率明显低于大剂量组,差异具有统计学意义(χ~2=5.127,P0.01);上消化道出血与患者年龄无相关性(P0.05),老年冠心病患者有消化道病史或吸烟史的服用阿司匹林肠溶片容易造成上消化道出血(P0.05),阿司匹林联合胃黏膜保护剂同时服用可有效降低上消化道出血发生率(P0.05).结论阿司匹林肠溶片联合胃黏膜保护剂,可降低上消化道出血发生率.     

建议用小剂量阿司匹林预防心血管疾病

系统温习研究资料，提示长期常规用阿司匹林预防心血管疾病，仅服小剂量者获益，大于81mg／d，效果并不更好，且增加消化道出血。     

抑酸药治疗使用阿司匹林、氯吡格雷的高危患者再次消化道出血的系统评价

目的明确消化道出血高危人群抗血小板治疗的方法，为临床选择治疗手段提供指导。方法纳入以消化道出血高危人群需抗凝治疗的患者为研究对象，对纳入研究的质量进行评价。通过计算机检索Pubmed、Medline及CBM数据库，搜集1984年～2007年的相天文献，采用表格对其中筛出的9篇符合要求的文献进行综合定量分析。结果对既往有消化性溃疡并出血病史患者，氯吡格雷和阿司匹林危险性相似，阿司匹林联合质子泵抑制剂预防复发性溃疡出血优于氯吡格雷。结论尽管氯吡格雷与阿司匹林对发生缺血事件的病人的危险性对比试验（CAPRIE）结果显示，存稳定的动脉粥样硬化疾病二级预防中，氯吡格雷优于阿司匹林，但绝对危险降低幅度较小，对于高危人群，使用小剂量阿司匹林加用质子泵抑制剂较使用氯吡格雷更安全。     

幽门螺杆菌感染和长期服用阿司匹林与上消化道出血关系研究

目的:探讨幽门螺杆菌(Hp)感染患者长期服用阿司匹林与上消化道出血的关系。方法:选取门诊每日服用100mg阿司匹林的患者,进行胃镜检查并检测Hp。根据Hp检测结果将3809例入选对象分为Hp阳性组和Hp阴性组,随访2年,观察上消化道出血情况;Hp阳性伴上消化道出血患者抗Hp治疗根除Hp后分组,分别给予法莫替丁40mg睡前顿服(干预组),或不加干预者作为对照组,2组均继续服用阿司匹林,随访2年,观察其再出血情况。结果:60岁以上老年患者服用小剂量阿司匹林上消化道出血率明显高于60岁以下患者(P<0.05);Hp阳性组2802例患者中上消化道出血146例(5.21%),Hp阴性组共1007例患者,上消化道出血为30例(2.98%),2组相比差异有统计学意义(P<0.05);144例患者根除Hp法莫替丁干预组72例,上消化道再出血2例(2.78%),对照组72例,上消化道再出血8例(11.1%),2组相比差异有统计学意义(P<0.05)。结论:60岁以上老年患者服用小剂量阿司匹林增加上消化道出血风险;Hp感染并长期服用小剂量阿司匹林可增加患者上消化道出血风险;法莫替丁干预能有效降低长期服用小剂量阿司匹林患者上消化道再出血风险。     

血清PG与INR、APTT在阿司匹林相关消化道出血中的预测价值研究

[目的]研究血清胃蛋白酶原(PG)、国际标准化比值(INR)、活化部分凝血酶原时间(APTT)在长期服用阿司匹林相关消化道出血中的预测价值。[方法]选取2018年8月1日～2020年5月1日诊治的长期口服低剂量肠溶阿司匹林治疗的213例患者,其中诊断阿司匹林相关消化道出血85例患者为出血组,未发生消化道出血128例患者作为对照组。对阿司匹林相关消化道出血的相关危险因素进行多因素Logistic回归分析,利用ROC曲线分析其预测价值。[结果]2组患者PGⅠ、PGⅡ、G17、INR、APTT均高于对照组,差异有统计学意义(P0.05)。Logistic回归模型结果显示PGⅠ、INR、APTT为其独立危险因素(P0.05)。ROC曲线结果示,PGⅠ、PGⅡ、INR、APTT对上消化道出血诊断的曲线下面积分别为0.733、0.623、0.720、0.637(P0.05),PGⅠ+INR+APTT曲线下面积为80.1%,灵敏度和特异度为81.2%、65.6%。[结论]联合PGⅠ与INR、APTT水平对阿司匹林相关消化道出血风险评估具有较高的预测价值。     

Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin?

Cyclo-oxygenase-2 selective inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) are associated with increased risk of acute cardiovascular events. Only aspirin offers primary and secondary cardiovascular prophylaxis, but trials have not answered directly whether low-dose aspirin is cardioprotective with COX-2 inhibitors. A large inception cohort study showed that concomitant use of aspirin reduced risk of cardiovascular events when given with rofecoxib, celecoxib, sulindac, meloxicam, and indometacin but not when given with ibuprofen. In large trials assessing gastrointestinal safety, there were fewer gastrointestinal events in patients using both COX-2 inhibitors and aspirin than in those using non-selective NSAIDs and aspirin; significantly fewer uncomplicated upper gastrointestinal events took place in the MEDAL trial. Analysis of VIGOR and two capsule endoscopy studies showed significantly less distal gastrointestinal blood loss with COX-2 inhibitors than with non-selective NSAIDs. Endoscopy trials showed that low-dose aspirin does not diminish the gastrointestinal benefits of COX-2 inibitors over non-selective NSAIDs. In an elderly epidemiological cohort receiving aspirin, both celecoxib and rofecoxib reduced risk of admission for gastrointestinal events. Comparison of the cardiovascular and gastrointestinal risks is difficult: likelihood and severity of cardiovascular events differ between individuals, agents, and exposure. Mortality associated with gastrointestinal events is less frequent than with cardiovascular events, but asymptomatic ulcers can result in severe complications. Data support the conclusion that COX-2 inhibitors are preferable to non-selective NSAIDs in patients with chronic pain and cardiovascular risk needing low-dose aspirin, but relative risks and benefits should be assessed individually for each patient.     

Low frequency of upper gastrointestinal complications in a cohort of high-risk patients taking low-dose aspirin or NSAIDS and omeprazole

BACKGROUND: There is very little information available on the incidence of complications and on the best prevention therapy in high-risk patients taking non-steroidal anti-inflammatory drugs (NSAIDs) and/or aspirin. Randomized-controlled trials in such patients are rare for ethical reasons. We studied the incidence of gastrointestinal complications in high-risk patients taking long-term low-dose aspirin or non-aspirin-NSAIDs combined with omeprazole in a real-life clinical setting. METHODS: This was a multicentre, prospective and observational study including 247 consecutive high-risk patients who had a clinical indication for long-term treatment with either low-dose aspirin or non-aspirin NSAIDs and omeprazole therapy. The occurrence of gastrointestinal complications was measured. RESULTS: In addition to a recent history of peptic ulcer bleeding, all patients had at least 1 other risk factor and 112 (45.3%) had 3 or more risk factors; 78.9% were taking low-dose aspirin and the remainder non-aspirin NSAIDs. Mean follow-up was 14.6 +/- 10.38 months. Three patients taking low-dose aspirin developed upper gastrointestinal bleeding (1.2%; 95% CI 0.3-3.5; 1.0 event/100 patients/year). This was similar to the rate observed in studies involving non-high-risk patients taking low-dose aspirin and higher than that observed in patients not taking low-dose aspirin. Two additional patients developed a lower gastrointestinal bleeding event (0.81% (0.04%-3.12%); 0.67 events/100 patients/year), which was within the range expected in NSAID users. CONCLUSIONS: The use of omeprazole in the high-risk patient taking low-dose aspirin or NSAIDs seems to be a safe therapeutic approach in this population and is associated with a low frequency of upper gastrointestinal complications.     

Low Frequency of Upper Gastrointestinal Complications in a Cohort of High-Risk Patients Taking Low-Dose Aspirin or NSAIDS and Omeprazole

Background: There is very little information available on the incidence of complications and on the best prevention therapy in high-risk patients taking non-steroidal anti-inflammatory drugs (NSAIDs) and/or aspirin. Randomized-controlled trials in such patients are rare for ethical reasons. We studied the incidence of gastrointestinal complications in high-risk patients taking long-term low-dose aspirin or non-aspirin-NSAIDs combined with omeprazole in a real-life clinical setting. Methods: This was a multicentre, prospective and observational study including 247 consecutive high-risk patients who had a clinical indication for long-term treatment with either low-dose aspirin or non-aspirin NSAIDs and omeprazole therapy. The occurrence of gastrointestinal complications was measured. Results: In addition to a recent history of peptic ulcer bleeding, all patients had at least 1 other risk factor and 112 (45.3%) had 3 or more risk factors; 78.9% were taking low-dose aspirin and the remainder non-aspirin NSAIDs. Mean follow-up was 14.6 ± 10.38 months. Three patients taking low-dose aspirin developed upper gastrointestinal bleeding (1.2%; 95% CI 0.3-3.5; 1.0 event/100 patients/year). This was similar to the rate observed in studies involving non-high-risk patients taking low-dose aspirin and higher than that observed in patients not taking low-dose aspirin. Two additional patients developed a lower gastrointestinal bleeding event (0.81% (0.04%-3.12%); 0.67 events/100 patients/year), which was within the range expected in NSAID users. Conclusions: The use of omeprazole in the high-risk patient taking low-dose aspirin or NSAIDs seems to be a safe therapeutic approach in this population and is associated with a low frequency of upper gastrointestinal complications.     

Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin?

Cyclo-oxygenase-2 selective inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) are associated with increased risk of acute cardiovascular events. Only aspirin offers primary and secondary cardiovascular prophylaxis, but trials have not answered directly whether low-dose aspirin is cardioprotective with COX-2 inhibitors. A large inception cohort study showed that concomitant use of aspirin reduced risk of cardiovascular events when given with rofecoxib, celecoxib, sulindac, meloxicam, and indometacin but not when given with ibuprofen. In large trials assessing gastrointestinal safety, there were fewer gastrointestinal events in patients using both COX-2 inhibitors and aspirin than in those using non-selective NSAIDs and aspirin; significantly fewer uncomplicated upper gastrointestinal events took place in the MEDAL trial. Analysis of VIGOR and two capsule endoscopy studies showed significantly less distal gastrointestinal blood loss with COX-2 inhibitors than with non-selective NSAIDs. Endoscopy trials showed that low-dose aspirin does not diminish the gastrointestinal benefits of COX-2 inibitors over non-selective NSAIDs. In an elderly epidemiological cohort receiving aspirin, both celecoxib and rofecoxib reduced risk of admission for gastrointestinal events. Comparison of the cardiovascular and gastrointestinal risks is difficult: likelihood and severity of cardiovascular events differ between individuals, agents, and exposure. Mortality associated with gastrointestinal events is less frequent than with cardiovascular events, but asymptomatic ulcers can result in severe complications. Data support the conclusion that COX-2 inhibitors are preferable to non-selective NSAIDs in patients with chronic pain and cardiovascular risk needing low-dose aspirin, but relative risks and benefits should be assessed individually for each patient.     

Digestive complications of aspirin

INTRODUCTION: This review focuses on aspirin-related gastrointestinal side-effects and the mechanism by which aspirin causes gastrointestinal damage. CURRENT KNOWLEDGE AND KEY POINTS: Aspirin causes direct gastric damage by topical irritant effects and indirect damage via systemic inhibition of cyclooxygenase synthesis and microcirculation injury. The question of a possible synergistic relation between the presence of Helicobacter pylori infection and aspirin use on gastric damage is not resolved. The pathogenesis of small intestinal and colonic damage is less well understood; an increase in intestinal permeability and free radical synthesis are suggested. Gastric damage predominates. Gastroduodenal lesions from aspirin have been documented in endoscopy studies. The lesions occur rapidly, even for low-dose aspirin. The association of aspirin consumption with upper gastrointestinal bleeding has been well established. The main risk factors are advanced age, concomitant use of nonsteroidal antiinflammatory drugs and history of ulcer. Low-dose aspirin are associated with increased risk of gastrointestinal bleeding and this risk is dose-dependant. Chronic aspirin consumption can cause iron deficiency anaemia. Uncomplicated gastric ulcer (but not uncomplicated duodenal ulcer) is associated with aspirin use, with relative risk 3. Other upper gastrointestinal complications have been reported: stenosis and perforation. Aspirin can also damage other areas of the gastrointestinal tract. Oesophageal injuries (oesophagitis and stricture) have been reported. Aspirin is associated with variceal bleeding episodes in patients with cirrhosis. The adverse effects of aspirin on the small bowel are perforation, bleeding, increasing permeability. The adverse effects of aspirin on the large intestine are perforation, bleeding, collagenous colitis and anorectal stenosis with suppositories containing aspirin. Direct clinical data regarding prophylaxis with co-administration of a protective drug are not yet available for aspirin. FUTURE PROSPECTS AND PROJECTS: Patients should be made aware of adverse gastrointestinal effects due to aspirin. Further studies regarding prophylactic therapy of low-dose aspirin induced gastroduodenal lesions, which identify a subset of patients who may be at higher risk than the low-dose aspirin population as a whole, are warranted.     

Upper gastrointestinal bleeding in patients treated by low-dose aspirin

AIM OF THE STUDY: To estimate the number of people treated by low-dose aspirin (<330 mg daily) in France and to evaluate the risk of upper gastrointestinal bleeding associated with low-dose aspirin treatment. SUBJECTS AND METHODS: One thousand six hundred and two patients with upper gastrointestinal bleeding were included between January and June 1996 in 4 French areas. Data about patients characteristics, drugs recently used, and bleeding lesions were prospectively collected. Five hundred seventy five cases were matched for sex, age and area with control people without previous upper gastrointestinal bleeding. Low-dose aspirin intake in the population was estimated from the control group. Aspirin intake in the previous 7 days in cases and in controls was compared by logistic regression, adjusted for other gastrotoxic drugs intake. RESULTS: Low-dose aspirin is taken by about 1.2 millions adults in France. In 1 602 patients, gastrointestinal bleeding was related to a peptic ulcer in 34%. Aspirin was associated with higher risk of upper gastrointestinal bleeding: OR=1.68 (1.03-2.74) with low-dose, and OR 1.42 (0.91-2.21) with higher doses. CONCLUSION: About 2.8% of the population is exposed to low-dose aspirin in France. This treatment seems to be associated with a high risk of upper gastrointestinal bleeding.     

New look at antiplatelet agent-related peptic ulcer: an update of prevention and treatment

Patients taking antiplatelet agents for the prevention of cardiovascular diseases who develop gastrointestinal bleeding represent a serious challenge in clinical practice. The initial step in reducing gastrointestinal risk of antiplatelet therapy is to assess whether the patient has a continued need for antiplatelet therapy. The next step is to eliminate the risk factors that may place the patient at increased gastrointestinal risk. In the management of bleeding ulcer patients with high-risk stigmata of recent hemorrhage, resuming antiplatelet agents at 3-5 days after the last dosing is a reasonable strategy. However, patients with low-risk stigmata can keep taking antiplatelet agents immediately following endoscopy. In the management of aspirin-related uncomplicated peptic ulcers in patients requiring antiplatelet therapies, continuing aspirin plus a powerful proton pump inhibitor is the choice of treatment. Patients who require antiplatelet agents for the prevention of cardiovascular diseases should be tested and treated for Helicobacter pylori infection before starting antiplatelet therapy. Additionally, those with high risks for upper gastrointestinal bleeding should receive co-therapy with a gastroprotective drug, preferably a proton pump inhibitor at standard dose. H2-receptor antagonist can significantly reduce upper gastrointestinal bleeding risk in patients taking low-dose aspirin but it is ineffective in the prevention of upper gastrointestinal bleeding in clopidogrel users. Although several retrospective studies reported that patients prescribed clopidogrel who also took proton pump inhibitors had significant increases in cardiovascular events, the current evidence from a prospective randomized trial does not justify a conclusion that proton pump inhibitors are associated with cardiovascular events among clopidogrel users.     

抗血小板治疗导致胃肠道损伤及其防治的研究进展

抗血小板药物治疗是进行心脑血管疾患预防及治疗的基石,广泛应用于临床.但长期使用可造成胃肠道损害,导致消化道出血等严重不良事件发生.如何在抗血小板治疗的同时进行消化系不良反应的防治,是目前临床面临的重要问题.本文就常用抗血小板药物阿司匹林和氯吡格雷导致胃肠道损害的作用机制、特点、防治措施等相关问题进行阐述,并对抗血小板药物相关消化道出血诊治指南和专家共识介绍.