强化剂量他汀类药物治疗急性冠状动脉综合征患者的有效性及安全性meta分析

发布时间：2018-12-06 20:03

【摘要】：背景:急性冠脉综合征(ACS)起病急骤,血清胆固醇水平及动脉粥样硬化斑块形成是其主要的危险因素。他汀类药物能够有效地降低胆固醇水平及稳定动脉粥样硬化斑块,同时还可以降低心血管事件的发生风险。近年来,强化剂量的他汀治疗已经逐步应用于西方发达国家,而我国仍处于常规剂量的治疗阶段。因此,对于ACS患者强化剂量他汀治疗是否较常规剂量他汀治疗能带来更大的获益及安全性值得我们进一步思考。目的:本研究拟收集相关RCT研究,针对强化剂量及常规剂量他汀治疗ACS患者的有效性及安全性进行meta分析,分析比较两组的降脂疗效和不良反应的发生情况。方法:全面检索Cochrane Library、PubMed、EMBASE、Web of Science、中国知网、中国生物医学文献数据库(CBM)、维普数据库(VIP)。检索时限为各数据库建库时间至2017年2月27日。两名研究者依据纳入和排除标准筛选及提取相关数据。文献质量评价采用Cochrane协作网偏倚风险评价工具进行。定量分析依据异质性检验及I2选择相对应的效应模型进行分析。P0.05为差异有统计学意义。结果:按照纳入与排除标准最终纳入8篇RCT,共9442例ACS患者。定量分析结果表明:有效性方面,强化剂量较常规剂量能更加显著的降低LDL-C(SMD=-0.76,95%CI:-1.04~-0.48,I2=96%)、TC(SMD=-0.66,95%CI:-0.72~-0.60,I2=18%)及TG(SMD=-0.20,95%CI:-0.25~-0.14,I2=0%)水平,HDL-C(SMD=0.01,95%CI:-0.05~0.06,I2=50%)水平在两组之间差异无统计学意义;安全性方面,强化剂量较常规剂量能更加显著降低全因死亡率(RR=0.75,95%CI:0.61~0.93,I2=0%)、MACE(RR=0.85,95%CI:0.76~0.96,I2=19%)、心源性死亡(RR=0.75,95%CI:0.59~0.95,I2=0%)及冠脉重建术(RR=0.87,95%CI:0.76~0.99,I2=0%)的发生风险,然而大剂量的他汀类药物治疗更加容易发生肝功能异常(RR=2.76,95%CI:1.85~4.12,I2=0%),同时,心肌梗死(RR=0.90,95%CI:0.78~1.05,I2=17%)、中风(RR=0.84,95%CI:0.58~1.21,I2=0%)及肌肉不良反应(RR=1.20,95%CI:0.91~1.58,I2=0%)在两组之间差异无统计学意义。敏感性分析提示本研究的结果稳健,具有较高的可信度。结论:强化剂量较常规剂量能更加显著的降低LDL-C、TC及TG水平;同时,强化剂量与常规剂量组相比较更优于降低全因死亡率、MACE、心源性死亡及冠脉重建术的发生风险,尽管强化剂量治疗更加容易发生肝功能异常。对于ACS患者进行强化剂量的他汀类药物治疗可以带来更大的获益,但同时也需密切监测肝功能的变化。上述结果仍需更多高质量、多中心、大样本的RCT进一步证实。
[Abstract]:Background: acute coronary syndrome (ACS) is a major risk factor for acute coronary syndrome (ACS). Serum cholesterol level and atherosclerotic plaque formation are the main risk factors. Statins can effectively reduce cholesterol levels and stabilize atherosclerotic plaques, as well as reduce the risk of cardiovascular events. In recent years, statin therapy with intensive dose has been gradually applied in western developed countries, but it is still in the stage of routine dose therapy in China. Therefore, whether the intensive dose of statins in patients with ACS can bring more benefits and safety than the conventional dose of statins deserves further consideration. Objective: to collect relevant RCT studies and to analyze the efficacy and safety of statin in the treatment of ACS by meta, and to compare the effect of lipid-lowering and the occurrence of adverse reactions between the two groups. Methods: a comprehensive search for Cochrane Library,PubMed,EMBASE,Web of Science, China knowledge Network, China Biomedical Literature Database, (CBM), Weip Database (VIP). The time limit for retrieval is the time for each database to be built up to February 27, 2017. The two researchers screened and extracted data based on inclusion and exclusion criteria. The evaluation of literature quality was carried out with the Cochrane collaboration Network bias risk Assessment tool. Quantitative analysis was based on heterogeneity test and I2 selection of the corresponding effect model analysis. P0.05 as the difference was statistically significant. Results: 9442 patients with ACS were included in 8 RCT, according to inclusion and exclusion criteria. The results of quantitative analysis show that the amount of enhancer can significantly reduce LDL-C (SMD=-0.76,95%CI:-1.04~-0.48,I2=96%), TC (SMD=-0.66,95%CI:-0.72~-0.60,) compared with the conventional dose in terms of effectiveness. There was no significant difference between the two groups in the levels of I2P (18%), TG (SMD=-0.20,95%CI:-0.25~-0.14,I2=0%) and HDL-C (SMD=0.01,95%CI:-0.05~0.06,I2=50%). In terms of safety, the dose of enhancer significantly reduced the all-cause mortality (RR=0.75,95%CI:0.61~0.93,I2=0%), MACE (RR=0.85,95%CI:0.76~0.96,I2=19%) compared with the conventional dose. Risk of cardiac death (RR=0.75,95%CI:0.59~0.95,I2=0%) and coronary artery reconstruction (RR=0.87,95%CI:0.76~0.99,I2=0%), However, large doses of statins are more likely to cause liver dysfunction (RR=2.76,95%CI:1.85~4.12,I2=0%) and myocardial infarction (RR=0.90,95%CI:0.78~1.05,I2=17%). There was no significant difference in stroke (RR=0.84,95%CI:0.58~1.21,I2=0%) and muscle adverse reaction (RR=1.20,95%CI:0.91~1.58,I2=0%) between the two groups. Sensitivity analysis shows that the results of this study are robust and reliable. Conclusion: the level of LDL-C,TC and TG can be significantly decreased by the dosage of fortifier compared with the conventional dose. At the same time, the enhanced dose is better than the conventional dose group in reducing the all-cause mortality, MACE, cardiogenic death and the risk of coronary artery reconstruction, although the enhanced dose treatment is more prone to liver dysfunction. Intensive doses of statins in patients with ACS can benefit more, but changes in liver function also need to be closely monitored. These results need to be further confirmed by high quality, multi-center, and large sample RCT.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.4

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