以統合分析的方法探究膽固醇酯轉移蛋白藥物治療血脂異常的療效與安全性

Meta-Analysisof Cholesteryl EsterTransfer Protein Inhibitors in theTreatment of Dyslipidemia (Evidence-Based Medicine)

魏菀葶(Wan-Ting Wei)

指導教授 ： 蔡崇弘

中山醫學大學/醫學院/醫學研究所/碩士(2014年)

https://doi.org/10.6834/CSMU.2014.00160

摘要

研究背景:血脂異常，一直是心血管疾病非常重要的危險因素之一，血脂異常容易造成動脈粥樣硬化，而後產生冠狀動脈心臟疾病（CHD）。過去發表的前瞻性觀察研究數據顯示，高密度脂蛋白（HDL-C）升高與冠心病事件風險降低有關。目前有多篇研究是以新研發的膽固醇酯轉移蛋白抑製劑(CETP－cholesteryl ester transfer protein) inhibitor：利用抑制膽固醇酯轉運蛋白的作用，來減少高密度脂蛋白（HDL-C）轉變為低密度脂蛋白（LDL-C），進而增加血漿中HDL-C的濃度。
研究方法：本研究的目的是利用統合分析的方式來評估Evacetrapib以及Anacetrapib這兩種上仍在臨床試驗階段的CETP inhibitor 的療效和安全性。利用MEDLINE，PUBMED 等資料庫進行搜索，納入關鍵字Anacetrapib OR Evacetrapib OR CETP inhibitor並限制條件為隨機控制試驗(RCT－Randomized Controlled Trial)，評讀後再利用嚴格的列入條件（inclusion）和排除條件（exclusion）標準來挑選。最後由343篇中挑選出5篇符合條件的文獻，以軟體RevMan進行統合分析，分別使用固定式模型（fixed-effects model）以及隨機式模型（random-effects model）的統計方式，再利用森林圖（forest plot）、漏斗圖（funnel plot ）的解讀，評估這種新型未上市的新藥(無論是單獨使用或與標準的降膽固醇劑 statin 類藥物一起使用)用來治療血脂異常的有效性以及安全性。
研究結果：顯示CETP inhibitor在使HDL-C濃度上升方面（N = 3710，P,0.00001，平均差（MD）= 0.78，95％CI [0.64，0.92]）的確是比未使用的組別上升情況來的顯著；而在LDL-C濃度下降方面（N = 3810，P ,0.00001，MD = -0.82，95％CI [-0.95，-0.68]），也顯示出與對照組相比有較為顯著的下降情況。而在安全性方面（N = 2081，P = 0.43，Odd Ratio= 1.11，95％CI [0.86，1.43]），從數據中可以發現使用CETP inhibitors的組別與對照組相比，並沒有顯著增加不良反應的情形發生。
結論：CETP inhibitor 治療組別的相關數據可以看出Evacetrapib以及Anacetrapib在於HDL-C濃度的上升和降低LDL-C濃度都的確是有其療效而且是顯著的，此外，在安全性方面的數據，也顯示其安全性。在文獻中還可發現Evacetrapib 在對於HDL-C濃度的上升的作用最強，雖然目前對於心血管事件的發生率降低的數據仍嫌不足也因為研究的時間而有限，我們仍是可以說與安慰劑或 statin 類藥物單藥治療相比，CETP inhibitor 作為單一療法或與 statin 類組合在升高HDL-C、降低 LDL-C 確實有其療效，只是對心血管事件的影響需要更深入更進一步的研究。

關鍵字

高血脂 ； Anacetrapib ； Evacetrapib ； CETP inhibitor ； 療效 ； 安全性

並列摘要

Background：Dyslipidemia is a major risk factor for atherosclerosis, which successively produces coronary heart disease (CHD).Increasing HDL cholesterol also can reduce your risk of heartdisease.Cholesteryl ester transfer protein (CETP) inhibitors are gaining substantial research interest for raising high density lipoprotein cholesterol levels. Method：The aim of the research was to estimate the efficacy and safety of cholesteryl ester transfer protein inhibitors as novel lipid modifying drugs. Systematic searches of all language’s literature for randomized controlled trials (RCT) were collected from MEDLINE, EBASE, PUBMED and references listed in eligible studies with the key words”Anacetrapib OR Evacetrapib OR CETP inhibitor”. The research assessed the search results and only included the double-blind RCTs by using cholesteryl ester transfer protein inhibitors as exclusively or co-administrated with statin therapy irrespective of gender in enrolled adult subjects. Our reaserch extracted the data by using predefined data fields. Of 343 studies identified, and 5 studies were included into the final meta-analysis. The meta-analysis was performed by Review Manager(REVMAN) software and a random effectmodel was selected preferentially . Visual inspection of thefunnel plot was used to detect the presence of publication bias. Result：The meta-analysis by forest plots revealed that CETP inhibitors increased the HDL-c levels (n = 3710, p,0.00001, mean difference (MD) = 0.78, 95% CI [0.64, 0.92]) and LDL-c (n = 3810, p,0.00001, MD=-0.82, 95% CI [-0.95, -0.68]) irrespective of mono-therapy or co-administration with statins. CETP inhibitor therapy did not increase the adverse events (n = 2081, p=0.43,Odds Ratio= 1.11, 95% CI [0.86, 1.43]) when compared with control. Conclusion：CETP inhibitors therapy is associated with significant increase in HDL-c and decrease in triglyceride and LDL-c with satisfactory safety and tolerability in patients with dyslipidemia. Evacetrapib has a more potent effect on HDL-C levels, whereas data on cardiovascular event rate reduction are limited. Compared with placebo or statin monotherapy, CETP inhibitors as monotherapy or in combination with statins increased HDL-C levels and decreased LDL-C levels. The effects on cardiovascular outcomes require further investigation.

並列關鍵字

CETP inhibitors ； Anacetrapib ； Evacetrapib ； Dyslipidemia ； safety ； efficacy

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