本文關(guān)鍵詞：不同質(zhì)子泵抑制劑或H2受體拮抗劑對冠脈支架術(shù)后氯吡格雷抗血小板藥效的影響　出處：《第四軍醫(yī)大學》2012年碩士論文　論文類型：學位論文

  更多相關(guān)文章： 冠心病 質(zhì)子泵抑制劑 H2受體拮抗劑 氯吡格雷 血小板功能

【摘要】：背景和目的 近年來，我國冠心病發(fā)病率呈逐年上升趨勢，尤其是急性冠脈綜合征（acutecoronary syndrome ACS），直接影響人們生活質(zhì)量，危害人類健康，是構(gòu)成居民死因的主要疾病。因此，冠心病的預防和治療尤為重要。血小板的活化、聚集與功能亢進，在冠心病ACS血栓形成過程中起始動作用，因此盡早抗血小板治療能顯著降低ACS的發(fā)病率和死亡率，經(jīng)皮冠狀動脈介入治療（percutaneous coronaryintervention, PCI）已成為治療冠心病的主要手段，指南推薦在PCI術(shù)前后應使用雙重抗血小板治療可預防血栓的形成[1]。伴隨抗血小板藥物的應用，消化道出血的患病率明顯增加，研究表明質(zhì)子泵抑制劑(proton pump inhibitors, PPI)與雙重抗血小板治療的聯(lián)合應用，可明顯減少上消化道出血風險[2,3]。PPI作為治療和預防胃和十二指腸損傷的首選藥物在臨床上被廣泛使用[4]。以往部分國內(nèi)外研究發(fā)現(xiàn)PPI甚至H2受體拮抗劑（H2receptor antagonists，H2RA）有可能降低氯吡格雷的抗血小板藥效，增加心血管不良事件的發(fā)生率和死亡率。而近期又有報道PPI并不影響氯吡格雷的抗血小板藥效，存在爭議[5-9]，引起心血管醫(yī)生的廣泛關(guān)注。本研究采用隨機對照的方法，探討ACS患者行PCI術(shù)后24h服用不同PPI或H2RA對冠脈支架術(shù)后氯吡格雷抗血小板藥效的影響，為冠心病患者雙聯(lián)抗血小板治療聯(lián)用PPI或H2RA臨床合理用藥提供臨床試驗依據(jù)。 方法 第一部分：不同PPI或H2RA對冠脈支架術(shù)后氯吡格雷抗血小板藥效的影響。入選2011年3月～11月在我院心血管內(nèi)科住院，符合中國心血管治療指南和建議的急性冠脈綜合征的診斷標準，臨床表現(xiàn)為不穩(wěn)定型心絞痛、非ST段抬高型心肌梗死和ST段抬高型心肌梗死，經(jīng)冠狀動脈造影術(shù)確診為冠心病，并成功行PCI術(shù)的患者。排除標準：高危出血患者、有抗血小板和抗凝藥物治療禁忌證、1月內(nèi)服用PPI或H2RA、入院前使用GPⅡb/Ⅲa受體拮抗劑、血小板計數(shù)＜100g/L、肌酐清除率＜250ml/min、肝臟疾病、胃腸道潰瘍、紐約心臟協(xié)會分級心功能Ⅳ級、懷孕、1年內(nèi)患腦血管意外�；颊呷朐汉缶o予阿司匹林300mg/d，氯吡格雷300mg～600mg負荷劑量后繼以75mg/d維持劑量雙重抗血小板治療，PCI術(shù)后24h在患者知情同意的情況下，按患者住院時間的先后順序隨機編號，受試對象按1:1比例隨機分為3組，分別給予以下藥物：A組：PPI組，A1組：埃索美拉唑（40mg/d）；A2組：雷貝拉唑(20mg/d）；B組：H2RA組，B1組：雷尼替丁(300mg/d）；B2組：法莫替丁(40mg/d）和C組：對照組(未用上述藥物）。于PCI術(shù)后24h（服用PPI或H2RA之前）及治療72h對各組患者晨起空腹肘靜脈采血2ml注入含0.05mol/LEDTA-Na2抗凝劑的塑料真空試管中，立即3000r/min離心15min，收集上層液（血漿，黃色），采用ELISA試劑盒檢測血小板表面活性標志蛋白：P-選擇素（CD62P）、血小板顆粒膜糖蛋白Ⅱb/Ⅲa（GPⅡb/Ⅲa），所有患者均抽取空腹靜脈血2ml注入含38g/L枸櫞酸鈉（9∶1）真空抗凝試管中，于2h內(nèi)采用電阻抗法檢測血小板聚集功能(PAgT，ADP誘導劑)，運用SPSS12.0統(tǒng)計軟件進行數(shù)據(jù)分析，比較其變化值。 第二部分：觀察冠脈支架術(shù)后1月，不同PPI或H2RA聯(lián)用氯吡格雷藥物之間相互作用的隨訪研究。按納入標準對入選行PCI術(shù)的ACS患者出院后，均給予阿司匹林300mg/d，氯吡格雷75mg/d維持劑量雙重抗血小板治療，受試對象繼續(xù)服用以下藥物：A組：PPI組，A1組：埃索美拉唑（40mg/d）；A2組：雷貝拉唑(20mg/d）；B組：H2RA組，B1組：雷尼替丁(300mg/d）；B2組：法莫替丁(40mg/d）和C組：對照組(未用上述藥物）。PCI術(shù)后24h（服用PPI或H2RA之前）及治療1月后對各組患者空腹靜脈采血，采用ELISA試劑盒檢測血小板表面活性標志蛋白：CD62P、GPⅡb/Ⅲa，，采用電阻抗法檢測血小板聚集功能：PAgT，運用SPSS12.0統(tǒng)計軟件進行數(shù)據(jù)分析，比較其變化值。 結(jié)果 第一部分：按納入標準共入選PCI術(shù)后ACS患者150例，給予抗血小板藥物治療，隨機入組情況：A組（60例）：PPI組， A1組：埃索美拉唑（n=30）；A2組：雷貝拉唑(n=30）；B組（60例）：H2RA組，B1組：雷尼替丁(n=30）；B2組：法莫替丁(n=30）和C組：對照組(未用上述藥物，n=30）�；颊呋�資料經(jīng)均衡性檢驗無偏倚，1.PPI組或H2RA組與對照組比較。PCI術(shù)后24h（PPI或H2RA治療前），A組、B組的CD62P、GPⅡb/Ⅲa及PAgT與C組比較，組間差異無統(tǒng)計學意義（P＞0.05）；PCI術(shù)后72h，各組上述指標治療前后差值△CD62P、△GPⅡb/Ⅲa及△PAgT與C組比較，組間差異無統(tǒng)計學意義（P＞0.05）；其中A組與B組治療前后差值△C D62P、△GP△b/△a及△P AgT比較，組間差異亦無統(tǒng)計學意義（P＞0.05）；2.不同類別PPI或H2RA與對照組比較。PCI術(shù)后24h（PPI或H2RA治療前），A1組、A2組、B1組、B2組的CD62P、GPⅡb/Ⅲa及PAgT與C組比較，組間差異無統(tǒng)計學意義（P＞0.05）；PCI術(shù)后72h，各組上述指標治療前后差值△CD62P、△GPⅡb/Ⅲa及△PAgT與C組比較，組間差異無統(tǒng)計學意義（P＞0.05）；其中A1組與A2組，B1組與B2組治療前后差值△C D62P、△GP△b/△a及△P AgT比較，組間差異無統(tǒng)計學意義（P＞0.05）。 第二部分：對入選的150例患者進行1個月隨訪，有18例患者因依從性差或失訪終止試驗。剩余患者132例：A組（54例）：PPI組，A1組：埃索美拉唑（n=28）；A2組：雷貝拉唑(n=26）；B組（49例）：H2RA組，B1組：雷尼替丁(n=25）；B2組：法莫替丁(n=24）和C組：對照組(未用上述藥物，n=29）。1. PPI組或H2RA組與對照組比較。PCI術(shù)后24h（PPI或H2RA治療前）A組、B組的CD62P、GPⅡb/Ⅲa及PAgT與C組比較，組間差異無統(tǒng)計學意義（P＞0.05）；PCI術(shù)后1月，各組上述指標治療前后差值△CD62P、△GPⅡb/Ⅲa及△PAgT與C組比較，組間差異無統(tǒng)計學意義（P＞0.05），其中A組與B組治療前后差值△C D62P、△G P△b/△a及△P AgT比較，組間差異亦無統(tǒng)計學意義（P＞0.05）。2.不同類別PPI或H2RA與對照組的比較。PCI術(shù)后24h (PPI或H2RA治療前)，A1組、A2組、B1組、B2組的CD62P、GPⅡb/Ⅲa及PAgT與C組比較，組間差異無統(tǒng)計學意義（P＞0.05）；PCI術(shù)后1個月，上述各組指標治療前后差值△CD62P、△GPⅡb/Ⅲa及△PAgT與C組比較，組間差異無統(tǒng)計學意義（P＞0.05），其中A1組與A2組，B1組與B2組治療前后差值△C D62P、△GP△b/△a及△PAgT比較，組間差異無統(tǒng)計學意義（P＞0.05）。 結(jié)論 1.不同PPI或H2RA與氯吡格雷短期內(nèi)聯(lián)用不降低氯吡格雷的抗血小板藥效。 2.不同PPI或H2RA與氯吡格雷聯(lián)用1個月藥物之間的相互作用不明顯，臨床聯(lián)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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