【作者】 张宁；

【导师】 姚桂华； 张鹏飞；

【作者基本信息】 山东大学 ， 内科学（专业学位）， 2013， 硕士

【摘要】 研究背景经皮冠脉介入术(percutaneous coronary intervention, PCI)操作可损伤冠脉血管内皮功能、诱发冠脉痉挛、斑块或血栓碎片导致远端冠脉栓塞,从而导致心肌缺血或心肌损伤。如何预防和减轻PCI围手术期心肌损伤已成为研究热点之一。心肌代谢类药物——曲美他嗪在治疗缺血性心脏病中的有效性和安全性已得到充分证实,但对其在预防和减轻PCI围手术期心肌损伤中的有效性则研究报道较少。由于不同临床研究所纳入的患者样本较小,研究结果不尽相同,尚不能为曲美他嗪在PCI围手术期中是否具有心肌保护作用提供充分的循证医学证据。研究目的收集关于曲美他嗪在PCI围手术期心肌保护作用的随机对照试验,应用1neta分析评价曲美他嗪在PCI围手术期的心肌保护作用,以及对PCI术后30天左心室收缩功能的影响。研究方法系统检索PubMed数据库、Cochrane临床对照试验中心注册库、自1980年1月至2012年12月期间公开发表的关于曲美他嗪在PCI手术相关心肌损伤中保护作用的随机对照临床试验。检索词包括“trimetazidine"或“vasorel"和"percutaneous coronary intervention"或"reperfusion"或"myocardio damage",通过文献纳入和排除标准决定纳入文献,并进行文献质量评价,提取与本研究相关的数据。应用RevMan5.1软件对PCI术中心电图缺血性ST-T改变、术中心绞痛症状发作、术后24小时肌钙蛋白I(cardiac troponin I, cTnl)升高、以及PCI术后30天左室射血分数(left ventricular ejection fraction, LVEF)等参数进行meta分析,来评价曲美他嗪在PCI围手术中在对心肌损伤的心肌保护作用。研究结果1.本研究共检索文献458篇,其中随机对照临床试验183篇。最终纳入5项随机对照临床试验,共包括514例接受PCI的冠心病患者,其中曲美他嗪治疗组265例,对照组249例。2.共有2项试验(曲美他嗪治疗组190例,对照组177例)对PCI术中心电图ST-T改变进行了评价。Meta分析结果显示,曲美他嗪治疗组在PCI术中出现缺血性ST-T改变的发生率显著低于对照组(32.1%比41.2%,OR：0.60,95%CI：0.37-0.95,P=0.03)。3.共有2项试验(曲美他嗪治疗组76例,对照组69例)对PCI术中心绞痛症状进行了研究。Meta分析显示,曲美他嗪治疗组在PCI术中出现心绞痛症状的发生率显著低于对照组(15.8%比43.5%,OR：0.16,95%CI：0.67-0.38,P<0.0001)。4.共有3项试验(曲美他嗪治疗组107例,对照组97例)评价了PCI术后30天LVEF测值的变化。Meta分析结果显示,曲美他嗪治疗组术后30天LVEF测值显著高于对照组(WMD：4.60,95%CI：2.68-6.53,P<0.00001)。5.共有3项试验(曲美他嗪治疗组185例,对照组177例)分析了PCI术后cTnl测值及术后24小时cTnI升高超过2倍正常值上限的患者数。尽管meta分析显示,PCI术后cTnl超过2倍正常值上限的发生率在两组间无显著性差异(24.3%比28.8%,OR0.43,95%CI：0.28-1.45,P=0.28),但3项试验中PCI术后不同时间段cTnl测值均显著低于对照组(P<0.05)结论该meta分析表明,PCI围手术期应用曲美他嗪可以显著降低术中心肌缺血所导致的缺血性ST-T改变与心绞痛的发生率,改善术后左室收缩功能,降低PCI术后cTnl水平。但由于纳入的临床试验数量少,包括的患者样本量较小,未能显示出cTnl水平升高超过2倍正常值上限的发生率,有待于更大样本的临床试验结果为曲美他嗪在PCI围手术期的心肌保护作用提供更多循证证据。该meta分析结果支持在PCI围手术期应用曲美他嗪进行治疗。更多还原

【Abstract】 Background and Objective:The operation of percutaneous coronary intervention (PCI) can induce coronary spasm, endothelial cell injury and the debris of atherosclerotic plaque or thrombus may cause coronary artery distal embolization, thereby resulting in myocardial ischemia or myocardial injury. The measures concerning cardioprotection during PCI procedure is of intriguing interest and has become one of the research hot topics in cardiology. The efficiency and safety of trimetazidine has been widely recognized in the treatment of patients with coronary artery disease (CAD). However, due to lack of sufficient evidence in clinical conditions, there is still doubt whether the administration of trimetazidine to patients undergoing PCI operation can minimize the myocardial ischemia or injure following successful PCI procedure. We aimed to performe a meta-analysis to evaluate the cardioprotective effect of trimetazidine on patients who underwent successful PCI.Methods:We systematically searched the literatures through the PubMed and Cochrane Central Registry of Clinical Trials for the published randomized controlled clinical trials (published from Jan1980to Dec2012) concerning the administration of trimetazidine to patients before and after PCI operations. The search terms including ’trimetazidine’ or ’vasorel’ and ’percutaneous coronary intervention’or’reperfusion’ or ’myocardio damage’. Data concerning the study design, patient characteristics, and outcomes were reviewed and extracted. The meta-analysis was performed using a software of RevMan5.1.7to evaluate the incidences of ischemic ST-T changes on electrocardiogram (ECG) and angina attacks during PCI, the incidence of elevated cardiac troponin I (cTnI) within24hours after PCI, and also the changes of left ventricular ejection fraction (LVEF)30days after PCI procedure.Results:1) We reviewed a total of458articles and183articles were randomized controlled clinical trials. Five trials which enrolled514patients with CAD were in accordance with the inclusion criteria and were included in this meta-analysis. Among of them,265subjects received trimetazidine (the trimetazidine group) and249subjects received placebos (the control group).2) The incidence of ischemic ST-T changes on ECG during the PCI procedure was assessed in2trials (including514patients in all,265patients in the trimetazidine group and249patients in the control group). The meta-analysis showed that the incidence of ischemic ST-T changes in the trimetazidine group was significantly lower than that in the control group (32.1%vs41.2%, OR:0.60,95%CI:0.37-0.95, P=0.03).3) The occurrence of angina attacks during the PCI procedure was evaluated in2trials (including145subjects,76subjects in the trimetazidine group and69patients in the control group). The results demonstrated that the incidence of angina attacks in the trimetazidine group was markedly lower than that in the control group (15.8%vs43.5%, OR:0.16,95%CI:0.67-0.38, P<0.0001).4) Three trials (204patients in all,107patients in the trimetazidine group and97patients in the control group) measured the LVEF values30days after the PCI procedure. The meta-analysis found that the mean value of LVEF in the trimetazidine group was significantly higher than that in the control group (WMD:4.60,95%CI:2.68-6.53, P<0.00001).5) A total of3trials (including362patients,185cases in the trimetazidine group and177cases in the control group) analysed the incidence of elevated cTnI≥2times the upper limit of normal, which was measured24hours after the PCI procedure. Although the meta-analysis demonstrated no significant difference between the trimetazidine group and the control group (24.3%vs28.8%, OR:0.43,95%CI:0.28-1.45, P=0.28), the cTnI measures tested on different time points following PCI precedures all showed much lower in the trimetazidine group than those in the control group in all the3trials (all P<0.05).Conclusion:Administration of trimetazidine before and after PCI provides a significant benefit over placebo in reducing the incidence of ischemic ST-T changes and angina attacks during the procedure, and improving the left ventricular systolic function after the procedure. The lack of evidence for reducing the incidence of elevated cTnI≥2times the upper limit of normal might be partly attributed to the small amout of trials and patients enrolled in this study.更多还原