本文選題：ST段抬高型心肌梗死 + 流行病學(xué)　； 參考：《吉林大學(xué)》2015年博士論文

【摘要】：【研究背景】 ST段抬高型心肌梗死（ST-segment elevation myocardial infarction, STEMI）的首要治療目標(biāo)是實(shí)現(xiàn)早期再灌注治療，而早期再灌注治療主要目的是盡快開(kāi)通梗死相關(guān)血管（infart-related artery, IRA），因此直接經(jīng)皮冠脈介入治療（percutaneous coronary intervention, PCI）成為STEMI的首選治療方案。在美國(guó)及歐洲發(fā)達(dá)國(guó)家如英國(guó)、瑞士等國(guó)，STEMI患者接受直接PCI的比例已高達(dá)70-90%，但我國(guó)由于受限于醫(yī)療條件（包括是否有能夠?qū)嵤┲苯覲CI的醫(yī)療機(jī)構(gòu)及24小時(shí)值班的急診介入治療團(tuán)隊(duì)等）和急診轉(zhuǎn)運(yùn)能力的不足，通常難以在指南推薦的心梗起病后12小時(shí)內(nèi)實(shí)施直接PCI。據(jù)衛(wèi)計(jì)委網(wǎng)報(bào)介入治療注冊(cè)數(shù)據(jù)顯示，我國(guó)每年僅有約3-5%的STEMI患者接受了直接PCI治療，與此同時(shí)，約有7-10%的STEMI患者接受了擇期PCI的治療，按照每年全國(guó)新發(fā)STEMI500,000-600,000例推算，每年約有35,000到60,000例STEMI患者接受了擇期PCI的治療，這是一組相當(dāng)龐大的數(shù)字。目前指南推薦：除存在自發(fā)或可誘發(fā)的進(jìn)行性心肌缺血表現(xiàn)、心源性休克或嚴(yán)重血液動(dòng)力學(xué)不穩(wěn)定、嚴(yán)重心力衰竭及室性心律失�？尚辛⒓葱蠵CI而無(wú)需考慮據(jù)起病的時(shí)間外，對(duì)于無(wú)心肌缺血表現(xiàn)，血液動(dòng)力學(xué)和心電穩(wěn)定患者，不推薦常規(guī)行擇期PCI。 但近年來(lái)對(duì)“晚期開(kāi)通血管”的獲益一直存在著爭(zhēng)議，該理論認(rèn)為開(kāi)通IRA能夠阻止或減緩梗死面積擴(kuò)展、梗死后心肌重塑和減少遠(yuǎn)期不良事件。但以O(shè)AT（Occluded Artery Trial）為首的一系列臨床隨機(jī)對(duì)照試驗(yàn)（randomized controlledtrail, RCT）對(duì)其結(jié)論提出了質(zhì)疑。薈萃分析認(rèn)為這種不一致的結(jié)論可能由于各臨床研究入組患者的高度選擇性及不同的心肌缺血狀況所引起的，需實(shí)施更大規(guī)模及入組更據(jù)代表性患者的RCT來(lái)證實(shí)這一結(jié)論，但進(jìn)一步開(kāi)展此類研究不得不面臨著巨大的倫理學(xué)障礙和極高的手術(shù)風(fēng)險(xiǎn)。如OAT研究實(shí)施過(guò)程中入選患者極其困難，平均每年各分中心入組不到2名患者。因此，貿(mào)然開(kāi)展更大規(guī)模RCT研究的可能性已微乎其微，尤其在發(fā)達(dá)國(guó)家早已普及直接PCI的今天。 真實(shí)世界研究隨著數(shù)據(jù)信息收集和計(jì)算能力的逐年提升而被醫(yī)學(xué)界所重新關(guān)注和重視。針對(duì)嚴(yán)格解釋性的RCT存在納入人群限制較多，用藥條件控制苛刻，使其結(jié)果雖內(nèi)部真實(shí)性較高，但外延性較差及應(yīng)用推廣受限，更多研究運(yùn)用真實(shí)世界研究方法分析來(lái)自臨床實(shí)踐中的海量數(shù)據(jù)用以觀察某一干預(yù)措施對(duì)預(yù)后的影響等，同時(shí)能夠克服入選患者人群代表性差、入組困難及研究結(jié)果時(shí)效性差等缺點(diǎn)。本研究也將基于真實(shí)世界研究方法，客觀地描述我國(guó)目前醫(yī)療條件和治療水平下STEMI后未接受早期再灌注治療且病情相對(duì)穩(wěn)定患者在臨床實(shí)踐中接受擇期PCI治療現(xiàn)況及預(yù)后影響因素，為今后相關(guān)指南的制定和臨床試驗(yàn)的設(shè)計(jì)開(kāi)展提供重要的線索和參考。 【研究目的】 觀察STEMI后未接受早期再灌注治療且病情相對(duì)穩(wěn)定的患者接受擇期PCI治療與預(yù)后情況，并觀察手術(shù)時(shí)機(jī)選擇及梗死相關(guān)血管支配區(qū)域的缺血程度對(duì)接受擇期PCI治療患者的預(yù)后影響。 【研究方法】 本研究為前瞻性觀察性隊(duì)列研究，第一和第二部分利用北京地區(qū)住院及死亡注冊(cè)數(shù)據(jù)信息，入選所有于2007-2010年間因STEMI住院的北京戶籍居民，排除合并患有心源性休克，嚴(yán)重心功能不全及室性心律失常，腫瘤或腎功能衰竭的患者。建立Cox等比例風(fēng)險(xiǎn)回歸模型和廣義估計(jì)方程用于比較組間的主要不良心血管事件（major adverse cardiovascular events, MACE）。研究擇期PCI（起病后2-28天）與單純藥物保守治療相比是否改善其預(yù)后及其最佳的手術(shù)時(shí)機(jī)。第三部分研究抽取一部分患者進(jìn)一步分析缺血程度是否為影響其擇期手術(shù)選擇的關(guān)鍵因素。 【研究結(jié)果】 本研究結(jié)果主要分為三大部分： 1.探討擇期PCI對(duì)STEMI后相對(duì)穩(wěn)定患者的預(yù)后影響 本部分研究共納入15,799例STEMI患者，其中5,417例接受起病后第2-28天的擇期PCI治療，另10,382例僅接受常規(guī)藥物治療。PCI組的2年累及MACE事件率顯著低于保守治療組[10.1％vs.20.4％，協(xié)變量調(diào)整后的危險(xiǎn)比（hazardratio，HR）為0.417，95％可信區(qū)間（confidence intervals, CI）為0.375-0.464，P0.001]。在經(jīng)傾向性評(píng)分匹配后的患者亞組中，調(diào)整的HR為0.494（95％CI為0.442-0.551，P0.001）。此外，混合效應(yīng)模型中發(fā)現(xiàn)PCI的使用呈與MACE事件的發(fā)生成負(fù)相關(guān)[調(diào)整后的比值比（odds ratio, OR），0.451，95％CI，0.392-0.538, P0.001]�？傊�，對(duì)于梗死后相對(duì)穩(wěn)定且未接受早期再灌注治療的患者，行擇期PCI可以顯著減少2年主要終點(diǎn)事件的發(fā)生，顯著提高無(wú)事件生存率及患者改善預(yù)后。 2.探討擇期PCI手術(shù)時(shí)機(jī)選擇現(xiàn)況及預(yù)后的影響 本部分研究共入選5,417例STEMI患者，分別有55.9％，35.4％和8.7％接受了起病后第2-7天，8-14天和15-28天的擇期PCI治療�；�資料分析時(shí)發(fā)現(xiàn)患者年齡和首診醫(yī)院等級(jí)與手術(shù)時(shí)間的選擇相關(guān)。三組間的1年累及MACE事件率無(wú)顯著性差異（7.1％，5.8％和6.3％，對(duì)數(shù)秩檢驗(yàn)P=0.272），且多因素調(diào)整后的手術(shù)時(shí)間本身也非MACE事件的獨(dú)立危險(xiǎn)因素（P0.05）�？傊瑩衿赑CI的時(shí)機(jī)選擇在臨床實(shí)踐中各不相同且受多種因素影響，研究未發(fā)現(xiàn)某一時(shí)間段的手術(shù)出現(xiàn)特別的臨床獲益，但起病后第二周內(nèi)的絕對(duì)事件數(shù)較少。 3.探討MaR對(duì)STEMI后相對(duì)穩(wěn)定患者行擇期PCI的預(yù)后影響 本部分研究共納入滿足入選標(biāo)準(zhǔn)的436例于起病后12-72小時(shí)就診且病情相對(duì)穩(wěn)定的STEMI患者，其中218例行擇期PCI治療和另218例僅接受適宜藥物治療。每名患者的MaR均由聯(lián)合Aldrich-ST評(píng)分和Selvester-QRS評(píng)分評(píng)估所得。主要終點(diǎn)是主要心血管不良事件包括心血管死亡，再�；蛟傺\(yùn)重建治療。在MaR35％的患者中，2年累及的主要終點(diǎn)事件率分別為9.2％（PCI組）和5.3％（OMT組）（調(diào)整后的HR PCI vs.OMT為1.855；95％CI，，0.617-5.575；P=0.271）；在MaR≥35％的患者中，2年累及的主要終點(diǎn)事件率分別為12.8％（PCI組）和23.1％（OMT組）（調(diào)整后的HR PCI vs.OMT為0.448；95％CI為0.228-0.884；P=0.021）�？傊�，心梗后晚期就診患者行擇期PCI的獲益與MaR相關(guān)。在MaR≥35％的患者中，接受PCI治療與OMT治療相比，可以顯著減少2年主要終點(diǎn)事件，改善患者預(yù)后，但在MaR 35％的患者，未發(fā)現(xiàn)上述獲益。 【研究結(jié)論】 綜上，我們發(fā)現(xiàn)擇期PCI可以顯著減少STEMI后相對(duì)穩(wěn)定患者2年的MACE終點(diǎn)事件的發(fā)生，而擇期PCI手術(shù)時(shí)機(jī)的選擇在實(shí)踐中差異巨大且受患者自身病情及首診醫(yī)院的影響，但并未發(fā)現(xiàn)某一手術(shù)時(shí)機(jī)對(duì)患者的預(yù)后產(chǎn)生顯著性影響，盡管第二周手術(shù)的絕對(duì)事件率較低。進(jìn)一步研究發(fā)現(xiàn)STEMI后相對(duì)穩(wěn)定的患者行擇期PCI的獲益與其自身MaR相關(guān)。在MaR≥35％的患者中，接受PCI治療與OMT治療相比，可以顯著減少2年MACE的發(fā)生并改善患者預(yù)后。在MaR35％的患者，未發(fā)現(xiàn)上述獲益。本系列研究描述了目前STEMI后相對(duì)穩(wěn)定患者的治療現(xiàn)況并分析了影響其預(yù)后的危險(xiǎn)因素，這將為今后相關(guān)指南的制定和臨床試驗(yàn)的設(shè)計(jì)開(kāi)展提供重要的線索及參考。
[Abstract]:BACKGROUND OF THE STUDY

The primary goal of ST - segment elevation myocardial infarction ( STEMI ) is to achieve early reperfusion therapy , and early reperfusion therapy is primarily aimed at providing immediate PCI for patients with STEMI as soon as possible . In the United States and European developed countries such as the UK , Switzerland and the like , there are only about 3 - 5 % of STEMI patients receiving direct PCI . At the same time , there are about 7 - 10 % of STEMI patients receiving direct PCI . At the same time , there are about 7 - 10 % of STEMI patients receiving elective PCI . At the same time , there are only about 3 - 5 % of STEMI patients undergoing elective PCI .

However , in recent years , there has been a debate on the benefit of " late - opening vessels " , which is considered to prevent or mitigate infarct size expansion , post - infarction myocardial remodeling , and reduce long - term adverse events . However , a series of clinical randomized controlled trials led by OAT is considered to be extremely difficult , with an average of less than 2 patients per year . Therefore , the possibility of a larger RCT study has been minimal , especially in developed countries today .

The real world research has been paid more attention and paid attention to by the medical community as the data information collecting and calculating ability increases year by year . For the strict interpretation of RCT , there are many disadvantages such as the limited population limit and the strict control of the medication condition , but also can overcome the disadvantages of the poor representation , the difficulty of enrollment and the poor timeliness of the research results .

Purpose of research

To observe the prognosis of patients with STEMI who did not receive early reperfusion therapy and the relatively stable condition of the disease , and observe the influence of the time of operation and the degree of ischemia on the infarct - related vascular innervation area on the prognosis of patients undergoing elective PCI .

Methodology of research

This study was a prospective observational cohort study in which the first and second sections were enrolled in all Beijing - based residents hospitalized for STEMI from 2007 - 2010 to exclude patients with cardiac shock , severe cardiac insufficiency and ventricular arrhythmias , tumors or renal failure . Cox proportional hazards regression models and generalized estimation equations were established to compare major adverse cardiovascular events ( MACEs ) between groups . The outcome of elective PCI ( 2 - 28 days post - onset ) and the optimal timing of surgery were studied . Part three of the study was to extract a part of the patients to further analyze whether the degree of ischemia was the key factor affecting the choice of elective surgery .

Outcome of the study

The results of this study are mainly divided into three parts :

1 . To investigate the influence of elective PCI on the prognosis of patients with STEMI after STEMI

In this part , 15,799 STEMI patients were enrolled . Of these , 5,417 patients received elective PCI on Day 2 - 28 after onset of onset and 10,382 were treated with routine medication only . The rate of events in 2 years in PCI group was significantly lower than that of conservative treatment group ( 10.1 % vs.20 . 4 % ) . The risk ratio after covariant adjustment was 0.417 , 95 % confidence intervals ( CI ) was 0.375 - 0.464 , P0.001 respectively . In the subgroup of patients with the matched propensity score , the adjusted HR was 0.494 ( 95 % CI 0.442 - 0.551 , P0.001 ) . In addition , the use of PCI was found in the mixed effect model to be negatively correlated with the incidence of the event , odds ratio ( OR ) , 0.4451 , 95 % CI , 0.392 - 0.538 , P0.001 respectively . In conclusion , PCI could significantly reduce the occurrence of 2 - year primary endpoint events , significantly improve the event - free survival rate and improve the prognosis for patients with relatively stable infarction and no early reperfusion therapy .

2 . To explore the effect of choosing the timing of elective PCI on the status quo and prognosis

In this part , 5 , 417 STEMI patients were enrolled , 55.9 % , 35.4 % and 8.7 % received elective PCI treatment on Days 2 - 7 , 8 - 14 and 15 - 28 days after onset of disease . There was no significant difference in the incidence rate between the three groups ( 7.1 % , 5.8 % and 6.3 % , log - rank test P = 0.272 ) .

3 . To investigate the effect of MaR on the prognosis of patients with STEMI after elective PCI

In this part , 436 patients with STEMI who met the criteria of inclusion were enrolled in 12 - 72 hours post - onset and were relatively stable , of whom 218 were treated with elective PCI and another 218 were treated with appropriate medication . The primary endpoint was major cardiovascular adverse events including cardiovascular death , reinfarction , or revascularization . The primary endpoint event rate in 2 years was 9.2 % in patients with MaR35 % ( PCI group ) and 5.3 % ( OMT group ) ( adjusted HR PCI vs . OMT = 1.855 ;
95 % CI , 0.617 - 5.575 ;
P=0.271)錛

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