幽门螺旋杆菌对服用抗血小板药物患者的影响

发布时间：2018-05-23 15:45

本文选题：幽门螺旋杆菌 + 阿司匹林　；参考：《武汉大学》2014年博士论文

【摘要】：H.pylori在全球范围内有一半人口感染或携带,在经济欠发达国家和老年人口中发病率更高。H.pylori可以通过粘附定植、尿素酶、毒力蛋白、诱导黏膜炎症及免疫反应等因素成为上消化道黏膜的重要致病因素,和消化性溃疡、慢性胃炎等密切相关,并被认为是胃癌的Ⅰ类致癌物。抗血小板药物广泛的应用于心脑血管疾病患者用来预防血栓的形成,并显著的降低了该类患者的病死率,但是随之带来了消化道不良事件的发生,尤其是上消化道出血的发生,严重时会导致患者的临床死亡,特别是在目前抗血小板治疗中常用的DAPT方案更容易出现。PPIs曾经被提倡应用于阿司匹林和氯吡格雷双抗患者中来减少上消化道出血的风险,但是随后的研究证实PPIs在减低抗血小板药物带来消化道不良事件的同时也增加了患者的心脑血管不良事件的发生,因此指南建议临床医生慎重选择在该类患者中使用PPIS。因此对非PPIs途径降低长期口服阿司匹林和氯吡格雷患者消化道出血和再出血的研究非常有临床意义。阿司匹林在体外试验中被证实对H. pylori的致病性有抑制作用,具体表现在直接对菌体的破坏、抑制尿素酶、干扰其定植粘附、减弱毒力蛋白的致病性、减弱H. pylori诱导的免疫及炎症反应等。但大量的临床研究证实H. pylori感染和长期小剂量阿司匹林对胃黏膜的损伤并没有拮抗因素,但是两者之间有无协同作用尚待明确。对抗血小板药物的依从性对于心脑血管疾病患者而言,至关重要,较低的依从性直接提高了心脑血管疾病患者的病死率和病残率,提高患者对抗血小药物的依从性十分重要,但是目前这方面研究局限在临床宣教和使用PPIs干预方面,鉴于PPIs可能影响抗血小板药物抗血栓效果,如何通过非PPIs途径来提高患者对抗血小板药物依从性是本次研究的重点之一。 H. pylori检测方式包括侵入性和非侵入性,但其机制是依赖尿素酶方式、形态学方式和免疫学方式。各种不同的检测方法各有优缺点,从而满足应用于不同的临床需求,本次研究会结合文献进行分析。 H. pylori根除率取决于细菌对抗生素是否耐药、治疗的时间、是否包含铋制剂、序贯性治疗、PPIs的选择及患者的服药依从性,提高H. pylori根除率需要从以上多方面来选择。急诊胃镜广泛的应用于临床实践,是早期诊断和治疗的关键手段,尤其是急诊内镜下止血更是临床消化道出血的重要治疗方式,但急诊胃镜应用于长期口服抗血小板药物的患者安全性有待研究,内镜下的止血方式、止血时机和急诊内镜的风险是否和普通患者一样,这些都需要进行研究和探讨。根除H.pylori能否增加胃黏膜在长期小剂量阿司匹林和其他抗血小板药物的修复能力,根除H. pylori能否使得患者对抗血小板药物依从性提高都是有待研究的问题。综上所述,长期使用抗血小板药物尤其是DAPT、H. pylori感染、上消化道出血与再出血、患者对抗血小板药物依从性等多方面问题都值得去研究和探讨。本次研究从以下两个方面就上述问题进行研究,并对其中部分细节问题进行探讨。第一部分：根除H. pylori对长期服用阿司匹林和氯吡格雷患者上消化道再出血发生率的影响目的：研究H. pylori感染在长期(大于或等于3月)服用阿司匹林和氯吡格雷患者上消化道再出血中意义,指导临床诊疗,降低该类患者上消化道再出血发生率。方法：选取2007年9月至2011年9月就诊于皖南医学院弋矶山医院并确诊为上消化道出血并有阿司匹林和氯吡格雷长期服药史(持续联合用药时间大于或等于3月)患者,急诊内镜及病理学检查明确上消化道出血病因,对有活动性出血患者进行内镜下止血。快速尿素酶试验、病理学及吉姆莎染色明确H. pylori感染。比较快速尿素酶实验、HE染色及吉姆莎染色对诊断H. pylori的差异,组间比较采用X2检验。选取H. pylori感染阳性患者分为实验组给以埃索美拉唑(20mg/BID)+克拉霉素(500mg/BID)+阿莫西林(1000mg/BID),治疗时间14天根除H. pylori,1月后C14呼气试验复查,未根除者采用埃索美拉唑(20mg, BID)+胶体次枸橼酸铋(240mg, BID)+P可莫西林(1.Og, BID)+呋喃唑酮(100mg, BID),治疗时间14天。对照组未根除H.pylori,随访两组患者6月内再出血发生率。组间比较采用X2检验。结果：有5例患者内镜下活动性出血,3例患者接受APC、1例患者接受黏膜下注射、1例患者接受金属钛夹封闭,5例患者均获得内镜下止血成功。在长期服用阿司匹林和氯吡格雷并发上消化道出血的患者中H. pylori感染率为70.51%(55/78),根除H. pylori后长期服用阿司匹林和氯吡格雷患者6月内上消化道再出血发生率7.69%(2/26),未根除H. pylori后长期服用阿司匹林和氯吡格雷患者6月内上消化道再出血发生率34.62%(9/26),统计分析示：干预组和对照组再出血率差异有统计学意义(X2=5.650, P=0.017), ITT (X2=5.893, P=0.015), H. pylori阴性组与干预组(X2=0.432, P=0.511), ITT (X2=0.568, P=0.451)差异无统计学意义,H. pylori阴性组与对照组(X2=1.630, P=0.202), ITT (X2=1.428, P=0.232)差异无统计学意义。结论：根除H. pylori能有效降低长期服用阿司匹林和氯吡格雷患者上消化道再出血发生率。第二部分：H.pylori感染和患者对抗血小板药物依从性关系的研究目的：明确H. pylori感染和患者对长期服用抗血小板药物的服药依从性的关系,研究根除H.pylori对患者长期服用抗血小板药物的依从性的影响。方法：选取皖南医学院弋矶山医院初次口服阿司匹林、阿司匹林联合氯吡格雷患者,均接受C14呼气试验,根据实验结果分为H. pylori感染阳性组和H. pylori感染阴性组,H. pylori感染阳性组随机分为实验组和对照组,对实验组进行以泮托拉唑(40mg, BID)+甲硝唑(0.4g,BID)+阿莫西林(1.0g,BID),共7天方案根除H. pylori,根治结束一月后C14呼气试验复查实验组,根据复查结果分为根除成功组和根除失败组。对根除成功组、根除失败组和对照组和H. pylori感染阴性组随访并进行依从性比较。组间比较采用X2检验。结果：初次服用阿司匹林患者295例,其中C14呼气试验阳性186例,C14呼气试验阴性109例,实验组中根除成功82例,根除失败43例。H. pylori感染阳性且根除成功组、H. pylori感染阳性且根除失败组、H. pylori感染阳性对照组和H. pylori感染阴性组对单纯口服阿司匹林的依从性分别为93.90%、83.33%、83.61%和93.46%。单纯口服阿司匹林患者中根除成功组患者依从性和H. pylori感染阳性对照组患者依从性显著差异(X2=3.949, P=0.047); H. pylori感染阳性对照组和H.pylori感染阴性组依从性差异有显著差异(X2=4.146,P=0.042),对随访丢失患者进行意向性分析后两组差异仍有统计学意义(X2=4.321,P=0.038),其他组间依从性差异均无统计学意义。阿司匹林联合氯吡格雷患者266例,其中C14呼气试验阳性173例,C14呼气试验阴性93例,实验组中根除成功74例,根除失败45例。H.pylori感染阳性且根除成功组、H. pylori感染阳性且根除失败组、H. pylori感染阳性对照组和H. pylori感染阴性组对单纯口服阿司匹林的依从性分别为90.41%、77.78%、77.36%和90.11%服用阿司匹林联合氯吡格雷患者中。根除成功组患者依从性和H.pylori感染阳性对照组患者依从性显著差异(X2=4.085, P=0.043), ITT (X2=4.023, P=0.045), H. pylori感染阳性对照组和H.pylori感染阴性组依从性差异有显著差异(X2=4.372, P=0.037), ITT (X2=4.391, P=0.036),其他组间依从性差异均无统计学意义。结论：H. pylori感染使得长期口服抗血小板药依从性下降,根除H. pylori成功可以提高患者口服抗血小板药物依从性。
[Abstract]:H . pylori has a higher incidence rate in economically less developed countries and older persons . H.pylori can be a major pathogenic factor in upper gastrointestinal mucosa , such as adhesion and colonization , urease , virulence protein , induced mucosal inflammation and immune response , and is considered to be a class I carcinogen of gastric cancer .

Anti - platelet drugs are widely used in the prevention of thrombosis in patients with cardiovascular and cerebrovascular diseases , and significantly reduce the mortality of patients with digestive tract diseases , but the subsequent studies confirm that PPIs are more likely to occur in patients with gastrointestinal adverse events , especially in the current antiplatelet therapy . PPIs have been promoted to use PPIS in patients with aspirin and clopidogrel . Therefore , it is recommended that clinicians carefully choose to use PPIS in these patients . Therefore , it is very important to study the non - PPIs route to reduce the digestive tract hemorrhage and rebleeding in patients with long - term oral aspirin and clopidogrel .

Aspirin has been shown to have an inhibitory effect on the pathogenicity of H . pylori in vitro . It has shown that the damage to the bacteria directly , the inhibition of urease , interfering with its colonization and adhesion , the pathogenicity of virulence protein , the weakening of H . pylori - induced immune and inflammatory response , etc . However , a large number of clinical studies have shown that H . pylori infection and long - term low - dose aspirin have no antagonistic effect on gastric mucosa injury , but there is no synergistic effect between them .

The compliance of antiplatelet drugs is very important for patients with cardiovascular and cerebrovascular diseases . The lower compliance directly increases the mortality and morbidity of patients with cardiovascular and cerebrovascular diseases . It is very important to improve the compliance of patients with anti - platelet drugs . In view of the fact that PPIs may influence the antithrombotic effect of antiplatelet drugs , how to improve the compliance of patients with platelet drug through non - PPIs pathway is one of the emphases of this study .

H.pylori detection methods include invasive and non - invasive , but the mechanism is dependent on the way of urease , morphology and immunology methods .

The eradication rate of H.pylori depends on whether the bacterium is resistant to antibiotics , the time it is treated , the choice of sequential therapy , the choice of PPIs and the patient ' s compliance , and the need to improve the eradication rate of H.pylori needs to be chosen in many ways .

Emergency gastroscopes are widely used in clinical practice . It is the key means of early diagnosis and treatment , especially emergency endoscopic hemostasis is an important way to treat gastrointestinal hemorrhage . However , the safety of emergency gastroscopes in patients with long - term oral antiplatelet drugs is to be studied .

Eradication of H.pylori can increase the ability of gastric mucosa to repair long - term small - dose aspirin and other anti - platelet drugs , and can eliminate H . pylori . Whether or not H . pylori can improve the compliance of patients with platelet drugs is a problem to be studied .

In conclusion , the long - term use of antiplatelet drugs , especially DAPT , H.pylori infection , upper gastrointestinal hemorrhage and rebleeding , the patient ' s fight against platelet drug compliance , is worth studying and exploring . This study has studied the above - mentioned problems from the following two aspects , and discusses some of the details .

Part I : Effect of H . pylori eradication on the incidence of upper gastrointestinal hemorrhage in patients with long - term administration of aspirin and clopidogrel

Objective : To study the significance of H . pylori infection in the treatment of upper gastrointestinal hemorrhage in patients with long - term ( greater than or equal to March ) administration of aspirin and clopidogrel , and to guide the clinical diagnosis and treatment to reduce the incidence of upper gastrointestinal hemorrhage .

Methods : From September 2007 to September 2011 , the patients were diagnosed as upper gastrointestinal hemorrhage , and aspirin and clopidogrel long - term administration history ( duration of continuous administration over or equal to 3 months ) were diagnosed . The results showed that the patients with active bleeding were treated with Esomeprazole ( 20mg / BID ) + clarithromycin ( 500mg / BID ) + amoxicillin ( 100mg , BID ) .

Results : There were 5 patients with active bleeding , 3 patients receiving APC , 1 patient receiving submucous injection , 1 patient receiving metallic titanium clip closed , 5 patients receiving endoscopic hemostasis successfully . There was no significant difference in the incidence of upper gastrointestinal hemorrhage in patients with upper gastrointestinal hemorrhage after long - term administration ( X2 = 5.650 , P = 0.015 ) , ITT ( X2 = 0.589 , P = 0.511 ) , ITT ( X2 = 0.568 , P = 0.451 ) , ITT ( X2 = 0.568 , P = 0.202 ) , ITT ( X2 = 1.428 , P = 0.232 ) , no significant difference .

Conclusion : Eradication of H.pylori can effectively reduce the incidence of upper gastrointestinal hemorrhage in patients with long - term aspirin and clopidogrel .

Part Two : H . pylori infection and patient ' s dependence on platelet drug compliance

Objective : To investigate the relationship between H . pylori infection and the compliance of patients with long - term antiplatelet drugs , and to study the effect of H . pylori on the compliance of patients with long - term antiplatelet drugs .

Methods : The first oral aspirin , aspirin and clopidogrel were selected for the treatment of H . pylori infection positive group and H . pylori infection - negative group , and H.pylori infection - positive group was divided into experimental group and control group . The experimental group was divided into experimental group and control group .

Results : There were significant differences in compliance between the positive control group ( X2 = 3.949 , P = 0.047 ) and H . pylori positive control group and H . pylori infection - positive control group ( X2 = 4.146 , P = 0.042 ) . There was no significant difference between the two groups ( X2 = 4.146 , P = 0.042 ) . There was a significant difference in compliance between the two groups ( X2 = 4.085 , P = 0.043 ) , ITT ( X2 = 4.023 , P = 0.037 ) , ITT ( X2 = 4.391 , P = 0.036 ) , and there was no significant difference between the other groups .

Conclusion : H . pylori infection can decrease the compliance of long - term oral anti - platelet drugs , and the success of H . pylori can improve the adherence of oral antiplatelet drugs to patients .
【学位授予单位】：武汉大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R573

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