调血脂药治疗代谢综合征的系统评价

目的系统评价调血脂药治疗代谢综合征（MS）的有效性和安全性。方法计算机检索Cochrane图书馆（2007年第4期）、MEDLINE（1966～2007）、EMbase（1984,2007）、中国生物医学文献数据库（1978～2007）、中国学术期刊全文数据库（1979～2007）和中文科技期刊全文数据库（1989—2007）,手工检索《中华内分泌代谢杂志》等相关杂志,纳入调血脂药治疗MS的随机或半随机对照试验,按Cochrane标准评价纳入研究质量。对同质研究采用RevMan4．2软件进行Meta分析,反之则只进行描述性的定性分析。结果共纳入9个随机对照试验,合计1420例MS患者。Meta分析结果显示：罗苏伐他汀与阿托伐他汀比较,两组对稳态模型胰岛素抵抗指数（HOMA index）、FPG、HbAlC无改善,罗苏伐他汀组升高HDL—c的疗效优于阿托伐他汀组,对TG的影响两组差异无统计学意义;辛伐他汀与阿托伐他汀比较,辛伐他汀组升高HDL—c的疗效优于阿托伐他汀组,辛伐他汀组降低TG的疗效差于阿托伐他汀组;普伐他汀与对照组比较,两组对腰围（WC）、体重指数（BMI）、FPG、HbAlC无影响。有2个研究为非诺贝特（200mg）与安慰剂比较,1个研究显示对HOMA index的影响两组差异无统计学意义,另1个研究显示非诺贝特组对QUICKI的改善优于安慰剂组;对BMI、FPG[WMD=0．0,95％CI（-0．15,0．15）]的影响,两组差异无统计学意义;非诺贝特组对TG[WMD=-1．77,95％CI（-2．21,-1．33）]、HDL—c[WMD=6．62,95％CI（2．07,11．17）]的改善优于安慰剂组。1个研究为非诺贝特（130mg,与进食同服／不与进食同服）与安慰剂比较,对SBP、WC的影响差异无统计学意义;非诺贝特组对HDL-c、TG的改善优于安慰剂组（P〈0．001）。阿托伐他汀、非诺贝特、阿托伐他汀＋非诺贝特比较,对MS患者比率[RR=0．99,95％CI（0．84,1．16）;RR=I．03,95％CI（0．88,1．20）;RR=1．01,95％CI（0．87,1．18）]、WC、FPG的影响3组差异无统计学意义;阿托伐他汀组、阿托伐他汀十非诺贝特组降低SBP／DBP的疗效优于非诺贝特组;非诺贝特＋阿托伐他汀组对HDL—c、TG的改善优于阿托伐他汀组。辛伐他汀、辛伐他汀＋非诺贝特比较,对FPG的影响两组差异无统计学意义,辛伐他汀＋非诺贝特组对HDL-c、TG的改善优于辛伐他汀组。奥利司他十非诺贝特与奥利司他比较,对降低MS患者比率、SBP／DBP、BMI、WC、FPG、HOMA index的疗效差异无统计学意义;奥利司他＋非诺贝特组降低TG的疗效优于奥利司他组（P〈0．05）;对HDL—c的影响两组差异无统计学意义。9个纳入研究均无对心血管事件和糖尿病发生率结局指标的报道。有6个研究报道了不良反应,结果显示调脂药耐受性良好,多数不良反应为轻至中度。结论本次系统评价所纳入的9个研究均缺乏对远期结局指标的观测,近期观察结果表明调脂药（他汀类、贝特类）对MS患者血脂（TG、HDL—c）改善有积极的效果,但对血压、胰岛素敏感性的疗效不确定;目前未发现对血糖、肥胖指标有改善作用。由于上述结论基本来自单个研究,样本量小,纳入研究总体质量不高,因此对待结论需谨慎。目前尚无足够的证据证明哪种药物更有效,非常有必要开展更多高质量、大样本、长期随访的RCT,以提供更可靠的证据。

Lipid-Modifying Therapy for Metabolic Syndrome: A Systematic Review

Objective To assess the efficacy and safety of lipid-modifying agents for metabolism syndrome. Methods We searched The Cochrane Library, MEDLINE, EMbase, the China Biological Medicine Database, VIP and CMAC to 2007. We also did some handsearching and additional searching. Randomized controlled trials of lipid- modifying therapy for metabolic syndrome were included. Two reviewers independently extracted data from the eligible studies and evaluated the quality of the included studies. Meta-analyses were performed for the results of homogeneous studies using The Cochrane Collaboration＇s RevMan 4.2.9 software. Results A total of 11 studies involving 1 422 patients with metabolic syndrome were included. The results indicated that there was no significant difference in TG between rosuvastatin and atorvastatin. However, rosuvastatin was more effective than atorvastatin on HDL-c improvement. Atorvastatin decreased TG levels greater than simvastatin, but simvastatin was superior to atorvastatin in HDL-c improvement. Two trials comparing fenofibrate with placebo were heterogeneous for some outcomes： one found no significant difference in improvements to HOMA-index, but the other trial indicated that fenofibrate was superior to placebo in improving QUICKI. However, the two trials revealed that fenofibrate favorably affected TG [WMD= -1.77, 95%CI （-2.21, -1.33）] and HDL-c [WMD= 6.62, 95%CI （2.07, 11.17）] compared with placebo. No significant differences among atorvastatin, fenofibrate, alone or in combination, were observed in the proportion of metabolic syndrome reduction [RR=0.99, 95%CI （0.84, 1.16）; RR=1.03, 95%CI （0.88, 1.20）; RR=1.01, 95%CI （0.87, 1.18）]. Atorvastatin plus fenofibrate was superior to atorvastatin alone in TG and HDL-c improvement. Simvastatin-fenofibrate combination produced greater effectiveness in improving of HDL-c and TG compared with simvastatin alone. The fenofibrateorlistat combination was similar to fenofibrate in reducing metabolic syndrome [RR=1.15, 95%CI （0.68, 1.95）] and TG improvement, but was more effective than fenofibrate in HOMA-index improvement. This review of the clinical trials shows that the majority of lipid-modulating drugs did not have favorable effects on FPG, BP, BMI and WC. Six studies reported side effects, showing that the side effects for lipid-regulating drugs were mild to moderate, and well tolerated. Conclusion Our results suggest that lipid-regulating drugs in general exhibit beneficial effects on TG and HDL-c, but not on blood glucose and central obesity. The therapeutic effects of lipid-regulating drugs on blood pressure and insulin sensitivity are uncertain and have no positive effects on FPG, BMI and WC. There is insufficient evidence in this review to recommend the use of lipid-modifying drugs for metabolic syndrome due to low methodological quality, small sample size and limited number of the trials. More high-quality and large-scale randomized controlled trials are required.