不同质子泵抑制剂或H2受体拮抗剂对冠脉支架术后氯吡格雷抗血小板药效的影响

发布时间：2018-01-10 11:34

  本文关键词：不同质子泵抑制剂或H2受体拮抗剂对冠脉支架术后氯吡格雷抗血小板药效的影响　出处：《第四军医大学》2012年硕士论文　论文类型：学位论文

  更多相关文章： 冠心病 质子泵抑制剂 H2受体拮抗剂 氯吡格雷 血小板功能

【摘要】：背景和目的 近年来，我国冠心病发病率呈逐年上升趋势，尤其是急性冠脉综合征（acutecoronary syndrome ACS），直接影响人们生活质量，危害人类健康，是构成居民死因的主要疾病。因此，冠心病的预防和治疗尤为重要。血小板的活化、聚集与功能亢进，在冠心病ACS血栓形成过程中起始动作用，因此尽早抗血小板治疗能显著降低ACS的发病率和死亡率，经皮冠状动脉介入治疗（percutaneous coronaryintervention, PCI）已成为治疗冠心病的主要手段，指南推荐在PCI术前后应使用双重抗血小板治疗可预防血栓的形成[1]。伴随抗血小板药物的应用，消化道出血的患病率明显增加，研究表明质子泵抑制剂(proton pump inhibitors, PPI)与双重抗血小板治疗的联合应用，可明显减少上消化道出血风险[2,3]。PPI作为治疗和预防胃和十二指肠损伤的首选药物在临床上被广泛使用[4]。以往部分国内外研究发现PPI甚至H2受体拮抗剂（H2receptor antagonists，H2RA）有可能降低氯吡格雷的抗血小板药效，增加心血管不良事件的发生率和死亡率。而近期又有报道PPI并不影响氯吡格雷的抗血小板药效，存在争议[5-9]，引起心血管医生的广泛关注。本研究采用随机对照的方法，探讨ACS患者行PCI术后24h服用不同PPI或H2RA对冠脉支架术后氯吡格雷抗血小板药效的影响，为冠心病患者双联抗血小板治疗联用PPI或H2RA临床合理用药提供临床试验依据。 方法 第一部分：不同PPI或H2RA对冠脉支架术后氯吡格雷抗血小板药效的影响。入选2011年3月～11月在我院心血管内科住院，符合中国心血管治疗指南和建议的急性冠脉综合征的诊断标准，临床表现为不稳定型心绞痛、非ST段抬高型心肌梗死和ST段抬高型心肌梗死，经冠状动脉造影术确诊为冠心病，并成功行PCI术的患者。排除标准：高危出血患者、有抗血小板和抗凝药物治疗禁忌证、1月内服用PPI或H2RA、入院前使用GPⅡb/Ⅲa受体拮抗剂、血小板计数＜100g/L、肌酐清除率＜250ml/min、肝脏疾病、胃肠道溃疡、纽约心脏协会分级心功能Ⅳ级、怀孕、1年内患脑血管意外。患者入院后均给予阿司匹林300mg/d，氯吡格雷300mg～600mg负荷剂量后继以75mg/d维持剂量双重抗血小板治疗，PCI术后24h在患者知情同意的情况下，按患者住院时间的先后顺序随机编号，受试对象按1:1比例随机分为3组，分别给予以下药物：A组：PPI组，A1组：埃索美拉唑（40mg/d）；A2组：雷贝拉唑(20mg/d）；B组：H2RA组，B1组：雷尼替丁(300mg/d）；B2组：法莫替丁(40mg/d）和C组：对照组(未用上述药物）。于PCI术后24h（服用PPI或H2RA之前）及治疗72h对各组患者晨起空腹肘静脉采血2ml注入含0.05mol/LEDTA-Na2抗凝剂的塑料真空试管中，立即3000r/min离心15min，收集上层液（血浆，黄色），采用ELISA试剂盒检测血小板表面活性标志蛋白：P-选择素（CD62P）、血小板颗粒膜糖蛋白Ⅱb/Ⅲa（GPⅡb/Ⅲa），所有患者均抽取空腹静脉血2ml注入含38g/L枸橼酸钠（9∶1）真空抗凝试管中，于2h内采用电阻抗法检测血小板聚集功能(PAgT，ADP诱导剂)，运用SPSS12.0统计软件进行数据分析，比较其变化值。 第二部分：观察冠脉支架术后1月，不同PPI或H2RA联用氯吡格雷药物之间相互作用的随访研究。按纳入标准对入选行PCI术的ACS患者出院后，均给予阿司匹林300mg/d，氯吡格雷75mg/d维持剂量双重抗血小板治疗，受试对象继续服用以下药物：A组：PPI组，A1组：埃索美拉唑（40mg/d）；A2组：雷贝拉唑(20mg/d）；B组：H2RA组，B1组：雷尼替丁(300mg/d）；B2组：法莫替丁(40mg/d）和C组：对照组(未用上述药物）。PCI术后24h（服用PPI或H2RA之前）及治疗1月后对各组患者空腹静脉采血，采用ELISA试剂盒检测血小板表面活性标志蛋白：CD62P、GPⅡb/Ⅲa，，采用电阻抗法检测血小板聚集功能：PAgT，运用SPSS12.0统计软件进行数据分析，比较其变化值。 结果 第一部分：按纳入标准共入选PCI术后ACS患者150例，给予抗血小板药物治疗，随机入组情况：A组（60例）：PPI组， A1组：埃索美拉唑（n=30）；A2组：雷贝拉唑(n=30）；B组（60例）：H2RA组，B1组：雷尼替丁(n=30）；B2组：法莫替丁(n=30）和C组：对照组(未用上述药物，n=30）。患者基线资料经均衡性检验无偏倚，1.PPI组或H2RA组与对照组比较。PCI术后24h（PPI或H2RA治疗前），A组、B组的CD62P、GPⅡb/Ⅲa及PAgT与C组比较，组间差异无统计学意义（P＞0.05）；PCI术后72h，各组上述指标治疗前后差值△CD62P、△GPⅡb/Ⅲa及△PAgT与C组比较，组间差异无统计学意义（P＞0.05）；其中A组与B组治疗前后差值△C D62P、△GP△b/△a及△P AgT比较，组间差异亦无统计学意义（P＞0.05）；2.不同类别PPI或H2RA与对照组比较。PCI术后24h（PPI或H2RA治疗前），A1组、A2组、B1组、B2组的CD62P、GPⅡb/Ⅲa及PAgT与C组比较，组间差异无统计学意义（P＞0.05）；PCI术后72h，各组上述指标治疗前后差值△CD62P、△GPⅡb/Ⅲa及△PAgT与C组比较，组间差异无统计学意义（P＞0.05）；其中A1组与A2组，B1组与B2组治疗前后差值△C D62P、△GP△b/△a及△P AgT比较，组间差异无统计学意义（P＞0.05）。 第二部分：对入选的150例患者进行1个月随访，有18例患者因依从性差或失访终止试验。剩余患者132例：A组（54例）：PPI组，A1组：埃索美拉唑（n=28）；A2组：雷贝拉唑(n=26）；B组（49例）：H2RA组，B1组：雷尼替丁(n=25）；B2组：法莫替丁(n=24）和C组：对照组(未用上述药物，n=29）。1. PPI组或H2RA组与对照组比较。PCI术后24h（PPI或H2RA治疗前）A组、B组的CD62P、GPⅡb/Ⅲa及PAgT与C组比较，组间差异无统计学意义（P＞0.05）；PCI术后1月，各组上述指标治疗前后差值△CD62P、△GPⅡb/Ⅲa及△PAgT与C组比较，组间差异无统计学意义（P＞0.05），其中A组与B组治疗前后差值△C D62P、△G P△b/△a及△P AgT比较，组间差异亦无统计学意义（P＞0.05）。2.不同类别PPI或H2RA与对照组的比较。PCI术后24h (PPI或H2RA治疗前)，A1组、A2组、B1组、B2组的CD62P、GPⅡb/Ⅲa及PAgT与C组比较，组间差异无统计学意义（P＞0.05）；PCI术后1个月，上述各组指标治疗前后差值△CD62P、△GPⅡb/Ⅲa及△PAgT与C组比较，组间差异无统计学意义（P＞0.05），其中A1组与A2组，B1组与B2组治疗前后差值△C D62P、△GP△b/△a及△PAgT比较，组间差异无统计学意义（P＞0.05）。 结论 1.不同PPI或H2RA与氯吡格雷短期内联用不降低氯吡格雷的抗血小板药效。 2.不同PPI或H2RA与氯吡格雷联用1个月药物之间的相互作用不明显，临床联用是合理安全的。
[Abstract]:Background and purpose
In recent years, China's disease incidence increased year by year, especially in patients with acute coronary syndrome (acutecoronary syndrome ACS), directly affect the quality of people's lives, harm to human health, is the main diseases of death causes of residents. Therefore, the prevention and treatment of coronary heart disease is particularly important. The activation of platelet aggregation, and hyperthyroidism, formation the dynamic role of starting process in ACS coronary thrombosis, so the early anti platelet therapy can significantly reduce the incidence of ACS and mortality after percutaneous coronary intervention (percutaneous CoronaryIntervention PCI) has become the main means of treatment of coronary heart disease, the guidelines recommend the formation of [1]. with application of antiplatelet drugs before and after PCI surgery should use dual antiplatelet therapy can prevent thrombosis, gastrointestinal bleeding prevalence increased, studies suggest that proton pump inhibitors (proton pump, inhibitors, and PPI) The combined application of dual antiplatelet therapy, can significantly reduce the digestive as the drug of choice for treatment and prevention of gastric and duodenal injury in clinical widely used [4]. in the past part of the domestic and foreign research found that PPI and H2 receptor antagonist [2,3].PPI (H2receptor antagonists risk of bleeding, H2RA) may reduce the antiplatelet efficacy of clopidogrel, and increase the incidence of the mortality rate of cardiovascular adverse events. Recent reports of PPI does not affect the efficacy of clopidogrel antiplatelet, controversial [5-9], caused widespread concern in the cardiovascular physicians. This study used the random control method, to investigate the ACS of PCI patients after taking 24h different PPI or H2RA on the efficacy of the antiplatelet effect of clopidogrel after coronary stent implantation, clinical the experimental basis for dual antiplatelet therapy in patients with coronary heart disease combined with PPI or H2RA clinical medication.
Method
The first part: the different PPI or H2RA on the efficacy of antiplatelet effects of clopidogrel after coronary stenting. Selected in March 2011 to November in the Department of cardiovascular medicine in our hospital, with Chinese cardiovascular treatment guidelines and recommendations for acute coronary syndrome diagnostic criteria, clinical manifestations of unstable angina and non ST elevation myocardial infarction and ST elevation myocardial infarction, coronary artery angiography diagnosis of coronary heart disease, and patients who received PCI. Exclusion criteria: Patients with high risk of bleeding, antiplatelet and anticoagulant therapycontraindications, taking PPI or H2RA in January, before admission using GP II b/ III a receptor antagonist, platelet count < 100g/L, creatinine clearance the rate of less than 250ml/min, liver disease, gastrointestinal ulcers, New York Heart Association classification of heart function grade, pregnancy, 1 years suffering from cerebrovascular accident. All the patients were given aspirin 300mg/d, clopidogrel Gray 300mg ~ 600mg 75mg/d loading dose followed by a maintenance dose of dual antiplatelet therapy after PCI 24h in patients with informed consent, according to the time sequence of a random number of hospitalized patients, according to the proportion of 1:1 subjects were randomly divided into 3 groups, were given the following drugs: A group: PPI group, A1 group: Esso esomeprazole (40mg/d); group A2: ray Bella with (20mg/d); group B: H2RA group, B1 group: ranitidine (300mg/d); group B2: famotidine (40mg/d) and C group (without the use of these drugs to PCI.) 24h after the operation (taking PPI or H2RA before) and treatment 72h fasting venous blood 2ml injection plastic vacuum tube containing 0.05mol/LEDTA-Na2 anticoagulant in patients in the morning, immediately 3000r/min centrifugal 15min, collect the upper liquid (plasma, yellow), the platelet surface active protein marker ELISA Kit: P- selectin (CD62P), platelet. Granule membrane glycoprotein b/ (a GP b/ a II III), all the patients were fasting venous blood 2ml injection containing 38g/L sodium citrate (9: 1) vacuum anticoagulant tube, to 2H by anti platelet aggregation resistance assay (PAgT, ADP inducer), using SPSS12.0 statistical software. The data analysis, the changes of value.
The second part: To observe after coronary stenting in January, follow-up study of interaction between clopidogrel combined with different PPI or H2RA. According to the inclusion criteria of the selected hospital underwent PCI surgery ACS patients after 300mg/d were treated with aspirin, clopidogrel maintenance dose of 75mg/d dual antiplatelet therapy, subjects continued to take the following drugs: A group: PPI group, A1 group: esomeprazole (40mg/d); group A2: ray Bella with (20mg/d); group B: H2RA group, B1 group: ranitidine (300mg/d); group B2: famotidine (40mg/d) and C group (without the drug) after.PCI 24h (before taking PPI or H2RA) and after treatment in January of fasting venous blood, using platelet surface active protein marker ELISA Kit: CD62P, GP II b/ III A, the resistance of platelet aggregation anti detection: PAgT, data using SPSS12.0 statistical software Analysis and comparison of its change value.
Result
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