發(fā)布時(shí)間：2018-01-15 20:20

  本文關(guān)鍵詞：房顫患者冠脈介入術(shù)后抗栓治療的臨床研究　出處：《青島大學(xué)》2017年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： Meta分析 房顫 口服抗凝藥 抗栓治療 心血管不良事件

【摘要】：第一部分房顫患者冠脈介入治療后不同抗栓治療方案的安全性和有效性分析目的回顧性探討經(jīng)皮冠脈介入治療的冠心病合并心房顫動(dòng)患者不同抗凝治療方案對(duì)主要不良心腦血管事件風(fēng)險(xiǎn)的影響,并評(píng)估不同抗凝治療方案的出血風(fēng)險(xiǎn)。方法回顧性選擇我院心內(nèi)科自2008年1月~2015年12月收治的冠心病行經(jīng)皮冠脈介入治療合并心房顫動(dòng)的246例患者,根據(jù)抗凝治療方案將患者分為三組,為雙聯(lián)抗血小板抗栓組(阿司匹林加氯吡格雷,簡(jiǎn)稱DT組);三聯(lián)抗栓組(華法林加阿司匹林加氯吡格雷,簡(jiǎn)稱TT組);華法林加單一抗血小板抗栓組(華法林加阿司匹林,或者華法林加氯吡格雷,簡(jiǎn)稱WS組),隨訪1年,評(píng)估三組患者的大出血發(fā)生風(fēng)險(xiǎn),隨訪觀察三組患者1年內(nèi)主要不良心腦血管事件(major adverse cardiac and cerebrovascular event,MACCE)風(fēng)險(xiǎn)。結(jié)果246例患者中,男性159例,女性187例,平均年齡為67.3±5.4歲,DT組207例,TT組11例,WS組28例。根據(jù)TIMI出血分級(jí)標(biāo)準(zhǔn),隨訪1年發(fā)現(xiàn)三組患者的大出血發(fā)生率分別為:DT組0%,TT組18.2%,WS組7.2%。三組間的大出血發(fā)生率有顯著統(tǒng)計(jì)學(xué)差異(P0.05)。隨訪期間,10例患者死亡,50例發(fā)生心肌梗死,40例行再次冠脈血運(yùn)重建,26例發(fā)生腦卒中,1例發(fā)生支架內(nèi)血栓。三組患者發(fā)生主要不良心腦血管事件的發(fā)生率分別為:DT組53.1%,TT組45.4%,WS組42.8%。三組間的主要不良心腦血管事件發(fā)生率無(wú)顯著統(tǒng)計(jì)學(xué)差異(P0.05)。然而,聯(lián)合應(yīng)用阿司匹林和氯吡格雷的二聯(lián)抗栓治療有增加腦缺血性卒中發(fā)生率的風(fēng)險(xiǎn)。結(jié)論房顫患者冠脈介入術(shù)后應(yīng)用三聯(lián)抗栓治療會(huì)顯著增加發(fā)生大出血的風(fēng)險(xiǎn),同時(shí)并未顯著降低隨訪1年的主要不良心腦血管事件發(fā)生率。雙聯(lián)抗血小板抗栓方案具有較低的大出血發(fā)生風(fēng)險(xiǎn),同時(shí)并未顯著增加主要不良心腦血管事件的發(fā)生風(fēng)險(xiǎn)。但阿司匹林和氯吡格雷的二聯(lián)抗栓治療有增加發(fā)生腦缺血性卒中發(fā)生率的風(fēng)險(xiǎn)。第二部分房顫患者冠脈介入術(shù)后抗栓治療的meta分析目的我們通過(guò)對(duì)28篇文獻(xiàn)涉及的31346人進(jìn)行的Meta分析,評(píng)估對(duì)于接受長(zhǎng)期口服抗凝治療和冠脈介入治療后的房顫患者,比較三聯(lián)抗栓治療和二聯(lián)抗栓治療的有效性和安全性。方法1.資料檢索:基于MEDLINE、EMBASE、Cochrane圖書(shū)館、Cochrane對(duì)照試驗(yàn)中心注冊(cè)庫(kù)及中文萬(wàn)方數(shù)據(jù)庫(kù),檢索關(guān)于抗栓治療的隨機(jī)對(duì)照研究和注冊(cè)性研究。2.文獻(xiàn)篩選:根據(jù)入選標(biāo)準(zhǔn)和排除標(biāo)準(zhǔn),應(yīng)用Endnote文獻(xiàn)管理管理軟件將入選文獻(xiàn)進(jìn)行整理,并對(duì)文獻(xiàn)進(jìn)行初步篩選和再次篩選,選擇所需的隨機(jī)對(duì)照試驗(yàn)文獻(xiàn)。3.資料收集:制備臨床數(shù)據(jù)資料提取表,包括基本信息、文獻(xiàn)基本特征、文獻(xiàn)的偏倚風(fēng)險(xiǎn)評(píng)價(jià)以及主要和次要臨床結(jié)局。主要臨床結(jié)局為不良心腦血管事件,次要臨床結(jié)局為全因死亡、心肌梗塞、缺血性卒中、支架內(nèi)血栓、大出血和不良事件。將每項(xiàng)試驗(yàn)的信息收集完整,若文獻(xiàn)相關(guān)信息不全,則聯(lián)系通訊作者獲取。4.文獻(xiàn)質(zhì)量評(píng)價(jià):按照改良的JADAD量表評(píng)價(jià)納入RCT的方法學(xué)質(zhì)量[5],包括(1)隨機(jī)序列產(chǎn)生:恰當(dāng)是2分,不清楚是1分,不恰當(dāng)是0分;(2)分配隱藏方式:恰當(dāng)是2分,不清楚是1分,不恰當(dāng)是0分;(3)盲法應(yīng)用:恰當(dāng)是2分,不清楚是1分,不恰當(dāng)是0分;(4)撤出和退出:描述是1分,未描述是0分�？偡�1-3分是低質(zhì)量研究,4-7分是高質(zhì)量研究。應(yīng)用紐卡斯?fàn)?渥太華量表(The Newcastle-Ottawa Scale,NOS)評(píng)價(jià)隊(duì)列研究的研究質(zhì)量。通過(guò)3大塊共8個(gè)條目評(píng)價(jià)隊(duì)列研究,具體包括研究人群選擇、可比性、暴露評(píng)價(jià)和結(jié)果評(píng)價(jià)。NOS對(duì)文獻(xiàn)質(zhì)量評(píng)價(jià)采用了星級(jí)系統(tǒng)的半量化原則,滿分為9顆星。5.數(shù)據(jù)的分析:應(yīng)用Stata 14.0軟件進(jìn)行統(tǒng)計(jì)分析。各項(xiàng)臨床結(jié)局指標(biāo)的評(píng)價(jià)采用森林圖表示,并對(duì)各研究進(jìn)行異質(zhì)性檢驗(yàn)和偏倚風(fēng)險(xiǎn)評(píng)估,I250%表示有顯著地異質(zhì)性。若有明顯異質(zhì)性則采用敏感性分析,剔除異質(zhì)性較大研究,并應(yīng)用隨機(jī)效應(yīng)模型分析數(shù)據(jù)。亞組分析評(píng)價(jià)不同抗栓治療方案和抗栓時(shí)間的效果。結(jié)果1.檢索后初步獲得894篇文獻(xiàn),通過(guò)閱讀題目、摘要,初篩剔除729篇文獻(xiàn);再通過(guò)閱讀全文剔除137篇文獻(xiàn),最終納入28篇文獻(xiàn),涉及31346人,平均隨訪14.2個(gè)月。2.兩組患者的基本特征,如年齡、性別以及高血壓等參數(shù)無(wú)顯著性差異。3.納入的1項(xiàng)隨機(jī)對(duì)照臨床試驗(yàn)中,研究質(zhì)量較高;27項(xiàng)隊(duì)列研究中,13項(xiàng)為前瞻性研究,方法學(xué)可靠性較高;14項(xiàng)為回顧性研究,研究質(zhì)量不高。4.25項(xiàng)研究報(bào)道了不良心腦血管事件,其中三聯(lián)抗栓組共14782例患者,3399例出現(xiàn)心腦血管事件(22.9%);二聯(lián)抗栓組有20706例患者,5511例患者出現(xiàn)心腦血管事件(26.6%)。隨機(jī)效應(yīng)模型分析結(jié)果提示與二聯(lián)抗栓治療相比,三聯(lián)抗栓治療對(duì)不良心腦血管事件的發(fā)生率無(wú)明顯影響(RR,0.95;95%可信區(qū)間(confidence interval,CI),0.84-1.07,P=0.39;I2=83.7%),雖然有明顯異質(zhì)性,但敏感性分析發(fā)現(xiàn)該異質(zhì)性并不影響臨床試驗(yàn)的最終結(jié)果。各種不同的抗栓治療方案中,三聯(lián)抗栓組的心腦血管不良事件的風(fēng)險(xiǎn)最低,華法林聯(lián)合阿司匹林二聯(lián)抗栓組的心腦血管事件風(fēng)險(xiǎn)最高。5.共25項(xiàng)研究報(bào)道了全因死亡的數(shù)據(jù)。其中三聯(lián)抗栓組共14782例患者,1416例死亡(9.5%);二聯(lián)抗栓組有20706例患者,2722例患者死亡(13.1%)。隨機(jī)效應(yīng)模型分析結(jié)果提示與二聯(lián)抗栓治療相比,三聯(lián)抗栓治療對(duì)全因死亡無(wú)明顯影響(RR,0.94;95%CI,0.78-1.12,P=0.46;I2=76.9%)。雖然有明顯異質(zhì)性,Begg檢驗(yàn)和Egger檢驗(yàn)未提示有顯著的發(fā)表偏倚,敏感性分析未發(fā)現(xiàn)對(duì)最終結(jié)果產(chǎn)生明顯影響的臨床試驗(yàn)。各種不同的抗栓治療方案中,華法林聯(lián)合氯吡格雷二聯(lián)抗栓組的全因死亡風(fēng)險(xiǎn)最低,華法林聯(lián)合阿司匹林二聯(lián)抗栓組的全因死亡風(fēng)險(xiǎn)最高。6.共21項(xiàng)研究報(bào)道了心肌梗死的數(shù)據(jù)。其中三聯(lián)抗栓組共8154例患者,448例患者出現(xiàn)心肌梗死(5.5%);二聯(lián)抗栓組有12186例患者,704例患者患者出現(xiàn)心肌梗死(5.8%)。固定效應(yīng)模型分析結(jié)果提示與二聯(lián)抗栓治療相比,三聯(lián)抗栓治療對(duì)心肌梗死無(wú)明顯影響(RR,0.94;95%CI,0.83-1.07,P=0.35;I2=35.4%)。Begg檢驗(yàn)和Egger檢驗(yàn)未提示有顯著的發(fā)表偏倚,敏感性分析未發(fā)現(xiàn)對(duì)最終結(jié)果產(chǎn)生明顯影響的臨床試驗(yàn)。各種不同的抗栓治療方案中,三聯(lián)抗栓組的心肌梗死風(fēng)險(xiǎn)最低。7.共19項(xiàng)研究報(bào)道了缺血性卒中的數(shù)據(jù)。其中三聯(lián)抗栓組共12769例患者,423例患者缺血性卒中(3.3%);二聯(lián)抗栓組有17056例患者,729例患者缺血性卒中(4.3%)。固定效應(yīng)模型分析結(jié)果提示與二聯(lián)抗栓治療相比,三聯(lián)抗栓治療明顯減少腦缺血性卒中的發(fā)生率(RR,0.80;95%CI,0.70-0.90,P0.001;I2=45.9%)。Begg檢驗(yàn)和Egger檢驗(yàn)未提示有顯著的發(fā)表偏倚,敏感性分析未發(fā)現(xiàn)對(duì)最終結(jié)果產(chǎn)生明顯影響的臨床試驗(yàn)。各種不同的抗栓治療方案中,三聯(lián)抗栓和華法林聯(lián)合氯吡格雷二聯(lián)抗栓組的缺血性卒中風(fēng)險(xiǎn)最低。8.共13項(xiàng)研究報(bào)道了支架內(nèi)血栓的數(shù)據(jù)。其中三聯(lián)抗栓組共4188例患者,72例患者出現(xiàn)支架內(nèi)血栓(1.7%);二聯(lián)抗栓組有7779例患者,145例患者有支架內(nèi)血栓(1.8%)。固定效應(yīng)模型分析結(jié)果提示與二聯(lián)抗栓治療相比,三聯(lián)抗栓治療對(duì)支架內(nèi)血栓無(wú)明顯影響(RR,0.97;95%CI,0.69-1.36,P=0.86;I2=14.6%)。Begg檢驗(yàn)和Egger檢驗(yàn)未提示有顯著的發(fā)表偏倚,敏感性分析未發(fā)現(xiàn)對(duì)最終結(jié)果產(chǎn)生明顯影響的臨床試驗(yàn)。各種不同的抗栓治療方案中,三聯(lián)抗栓組的支架內(nèi)血栓風(fēng)險(xiǎn)最低。9.共26項(xiàng)研究報(bào)道了大出血的數(shù)據(jù)。其中三聯(lián)抗栓組共14831例患者,1742例出現(xiàn)大出血(11.7%);二聯(lián)抗栓組有18390例患者,1259例患者大出血(6.8%)。隨機(jī)效應(yīng)模型分析結(jié)果提示與二聯(lián)抗栓治療相比,三聯(lián)抗栓治療明顯增加大出血風(fēng)險(xiǎn)(RR,1.71;95%CI,1.41-2.06,P0.001;I2=69.9%)。Begg檢驗(yàn)和Egger檢驗(yàn)未提示有顯著的發(fā)表偏倚,敏感性分析未發(fā)現(xiàn)對(duì)最終結(jié)果產(chǎn)生明顯影響的臨床試驗(yàn)。各種不同的抗栓治療方案中,三聯(lián)抗栓組的大出血風(fēng)險(xiǎn)最高,華法林聯(lián)合氯吡格雷二聯(lián)抗栓治療的大出血風(fēng)險(xiǎn)最低。10.不良事件包括全因死亡、心肌梗死、支架內(nèi)血栓、缺血性卒中和大出血。共24項(xiàng)研究報(bào)道了不良事件的數(shù)據(jù)。其中三聯(lián)抗栓組共14627例患者,5136例有不良事件(35.1%);二聯(lián)抗栓組有18186例患者,6533例患者死亡(35.9%)。隨機(jī)效應(yīng)模型分析結(jié)果提示與二聯(lián)抗栓治療相比,三聯(lián)抗栓治療有增加不良事件的趨勢(shì)(RR,1.07;95%CI,0.97-1.17,P=0.18;I2=82.9%)。Begg檢驗(yàn)和Egger檢驗(yàn)未提示有顯著的發(fā)表偏倚,敏感性分析未發(fā)現(xiàn)對(duì)最終結(jié)果產(chǎn)生明顯影響的臨床試驗(yàn)。各種不同的抗栓治療方案中,三聯(lián)抗栓組的不良事件風(fēng)險(xiǎn)最高,華法林聯(lián)合氯吡格雷二聯(lián)抗栓治療的不良事件風(fēng)險(xiǎn)最低。11.根據(jù)不同隨訪時(shí)間,我們對(duì)抗栓治療對(duì)心腦血管事件的影響進(jìn)行亞組分析。短期隨訪為隨訪時(shí)間12個(gè)月,中長(zhǎng)期隨訪為隨訪時(shí)間≥12個(gè)月。其中短期隨訪組有6項(xiàng)研究,中長(zhǎng)期隨訪組有22項(xiàng)研究。短期隨訪亞組中,隨機(jī)效應(yīng)模型分析結(jié)果提示與二聯(lián)抗栓治療相比,三聯(lián)抗栓治療有減少心腦血管事件的風(fēng)險(xiǎn)的趨勢(shì)(RR,0.76;95%CI,0.55-1.05,P=0.10;I2=31.9%)。中長(zhǎng)期隨訪亞組中,隨機(jī)效應(yīng)模型分析結(jié)果提示與二聯(lián)抗栓治療相比,三聯(lián)抗栓治療對(duì)心腦血管事件發(fā)生率無(wú)明顯影響(RR,0.98;95%CI,0.85-1.12,P=0.72;I2=86.2%)。因此,各種不同的抗栓治療方案中,在短期隨訪時(shí)(12個(gè)月),華法林、氯吡格雷和阿司匹林三聯(lián)抗栓治療的主要心腦血管事件的風(fēng)險(xiǎn)最低。在中長(zhǎng)期隨訪時(shí)(12≥個(gè)月),華法林聯(lián)合氯吡格雷二聯(lián)抗栓治療的主要心腦血管的風(fēng)險(xiǎn)最低。結(jié)論1.長(zhǎng)期應(yīng)用抗凝藥的房顫患者接受冠脈介入治療后,可在短期內(nèi)(12個(gè)月)應(yīng)用華法林、氯吡格雷和阿司匹林三聯(lián)抗栓治療,可降低短期的不良心腦血管事件的風(fēng)險(xiǎn);可在中長(zhǎng)期內(nèi)(≥12個(gè)月)應(yīng)用華法林和氯吡格雷的二聯(lián)抗栓治療,可降低中長(zhǎng)期的不良心腦血管事件的風(fēng)險(xiǎn)。2.三聯(lián)抗栓治療較二聯(lián)抗栓治療,增加大出血風(fēng)險(xiǎn),是否可以應(yīng)用新型口服抗凝藥降低大出血風(fēng)險(xiǎn),尚需更多高質(zhì)量的臨床試驗(yàn)驗(yàn)證。
[Abstract]:The first part of the treatment of patients with atrial fibrillation after coronary intervention of different antithrombotic treatment efficacy and safety of objective to evaluate the effect of percutaneous coronary intervention combined with atrial fibrillation in patients with coronary heart disease treatment of different anticoagulant regimens on major adverse cardiovascular event risk, and to assess the risk of bleeding of different anticoagulant regimens. Methods a retrospective selection the Department of Cardiology in our hospital from January 2008 ~2015 year in December from coronary heart disease undergoing percutaneous coronary intervention in 246 patients with atrial fibrillation patients according to anticoagulation therapy were divided into three groups, double anti platelet thrombus group (aspirin plus clopidogrel, referred to as DT group); triple antithrombotic group (Wafa Lin Fagafaga A Spelinga clopidogrel, referred to as TT group); Huafalinjia single antiplatelet antithrombotic group (aspirin or clopidogrel Huafalinjia, Huafalinjia, referred to as WS group), followed up 1 Year, evaluation of three groups of patients with major bleeding risk, observe three groups of patients within 1 years of major adverse cardiovascular events (major adverse cardiac and cerebrovascular event, MACCE). Results of the 246 patients, 159 were male, 187 were female, the average age was 67.3 + 5.4, DT group 207 cases. 11 cases of TT group, WS group of 28 cases. Hemorrhage according to the TIMI classification standard, 1 years of follow-up found that three groups of patients with major bleeding rates were: DT group 0%, TT group 18.2%, WS group 7.2%. between the three groups in the rate of major bleeding with significant difference (P0.05). During the follow-up, 10 patients death occurred in 50 cases of myocardial infarction, 40 patients underwent revascularization, 26 cases of stroke, 1 cases of stent thrombosis. Three groups of patients with major adverse cardiovascular event rates were: DT group 53.1%, TT group 45.4%, the incidence rate of WS group 42.8%. between the three groups of major adverse cardiovascular and vascular events There was no statistically significant difference (P0.05). However, the combination of aspirin and clopidogrel two antithrombotic therapy have increased ischemic stroke risk. Antithrombotic therapy will increase the risk of bleeding application AF patients with coronary intervention, the incidence rate did not significantly reduce the follow-up of 1 years the adverse cardiovascular and cerebrovascular events. Dual antiplatelet and antithrombotic scheme has a low risk of major bleeding, but did not significantly increase the risk of major adverse cardiovascular events. But aspirin and clopidogrel two antithrombotic therapy have increased the occurrence of cerebral ischemic stroke risk. Objective to analyze the Meta we conducted in 31346 people involved in 28 articles of antithrombotic therapy in patients with coronary meta analysis second patients with atrial fibrillation after PCI, evaluation for receiving long-term oral anticoagulant therapy and coronary artery After interventional therapy in patients with atrial fibrillation, comparison of triple antithrombotic therapy and two antithrombotic therapy is effective and safety. 1. methods of information retrieval based on MEDLINE, EMBASE, Cochrane library, Cochrane Central Register of controlled trials and Chinese Wanfang database, on antithrombotic therapy randomized controlled study and registration of.2. document retrieval: screening according to inclusion criteria and exclusion criteria, the application of Endnote document management software will be included in literature, and the literature were used for preliminary screening and re screening, select the desired randomized controlled trials of.3. data collection: the preparation of clinical data extraction form, including basic information, basic characteristics of literature, risk of bias review of the literature and the primary and secondary clinical outcomes. The main clinical outcomes for adverse cardiovascular events, secondary outcomes were all-cause death, myocardial infarction, ischemic stroke, stent 鍐呰��鏍，

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