调血脂药治疗代谢综合征的系统评价_《中国循证医学杂志》

作者：

勾忠平 ¹ ,  李秀钧 ² , 吴泰相 ³

1. 四川大学华西医院GCP中心（成都 610041）2. 四川大学华西医院内分泌科（成都 610041）3. 四川大学华西医院中国循证医学中心（成都 610041）;

关键词：

代谢综合征调血脂药他汀类贝特类系统评价随机对照试验

DOI：

10.7507/1672-2531.20090067

视频：

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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RevMan 4.2 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1 420 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、HbA1C 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、HbA1C 无影响。有2个研究为非诺贝特（200 mg）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（130 mg，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 lt;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=1.03，95%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+ 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+ 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 lt;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。

引用本文： 勾忠平,李秀钧,吴泰相. 调血脂药治疗代谢综合征的系统评价. 中国循证医学杂志, 2009, 09(3): 355-364. doi: 10.7507/1672-2531.20090067 复制

1.	systemic inflammation: reversal with bezafibrate therapy in a randomized controlled trial. Am J Med, 2002, 112(4): 275-280.
2.	Rizos E, Kostoula A, Elisaf M, et al. Effect of ciprofibrate on C-reactive protein and fibrinogen levels. Angiology, 2002, 53(3): 273-277.
3.	Avogaro A, Miola M, Favaro A, et al. Gemfibrozil improves insulin sensitivity and flow- mediated vasodilatation in type 2 diabetic patients. Eur J Clin Invest, 2001, 31(7): 603-609.
4.	Jonkers IJ, Mohrschladt MF, Weterndorp RG, et al. Severe hypertriglyceridemia with insulin resistance is associated with.
5.	Tenenbaum A, Motro M, Fisman EZ, et al. Peroxisome proliferatoractivated receptors ligand bezafibrate for prevention type 2 diabetes mellitus in patients with coronary artery disease. Circulation, 2004, 109(18): 2197-2202.
6.	Fruchart JC, Staels B, Duriez P. The role of fibric acids in atherosclerosis. Curr Atherosler Rep, 2001, (3): 83-92.
7.	Wang TD, Chen WJ, Lin JW, et al. Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles. Atheroslerosis, 2003, 170(2): 315-323.
8.	Rubins HB, Rubins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Trail Study Group. N Engl J Med, 1999, 341(6): 410-418.
9.	Anonymous. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate infarction Prevention( BIP) study. Circulation, 2000, 102(1): 21-27.
10.	Diabetes Atherosclerosis Intervention Study Group. Lancet, 2001, 357: 90-96.
11.	The FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet, 2005, 366(9500): 1849-1861.
12.	Heart Protection Study Collaborative Group. MRC／BHF Heart Protection Study of cholesterol lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet, 2003, 361(9374): 2005-2016.
13.	Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertension patients who have average or lower-than-average cholesterol concentration, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet, 2003, 361(9364): l149-1158.
14.	Canner PL, Furberg CD, Terrin ML, et al. Benefits of niacin by glycemic status in patients with healed myocardial infarction (from the Coronary Drug Project). Am J Cardiol, 2005, 95(2): 254-257.
15.	Alberti KGMM, Zimmet PZ, WHO Consultation. Definition, diagnosis and classification of diabetes mellitus and itscomplications.Part 1:diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med, 1998, (15): 539-553.
16.	Expert Panel on Detection, Evaluation, and Treatment of High Blood cholesterol in Adults (Adult treatment Panel Ⅲ). Executive summary of the third report of the National Cholesteral Eduation Program (NECP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. J Am Med Assoc, 2001, 285(19): 2486-2497.
17.	Barclay L. Medscape Medical News. New definition of the metabolic syndrome: a newsmaker interview with Sir George Alberti, MA, DPhil, BMBCh. Available at: http://www.medscape.com/viewarticle/504382 Accessed July 8, 2005.
18.	吴泰相, 刘关键. 隐蔽分组（分配隐藏）和盲法的概念、实施与报告. 中国循证医学杂志, 2007, 7(3): 222-225.
19.	Filippatos TD, Kiortsis DN, Liberopoulos EN, et al. Effects of orlistat, micronised fenofibrate and their combination on metabolic parameters in overweinght and obese patients with the metabolic syndrome:the FenOrli study. Current Medical Research and Opinion, 2005, 21 (12): 1997-2006.
20.	Filippatos TD, Gazi IF, Liberopoulos EN, et al. The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic syndrome. Atherosclerosis, 2007, 193(2): 428-437.
21.	Athyros VG, Mikhailidis DP, Papage-orgiou AA, et al. Targeting vascular risk in patients with metabolic syndrome but without diabetes. Metabolism Clinical and Experimental, 2005, 54(8): 1065-1074.
22.	Athyros VG, Mikhailidis DP, Didan-gelos TP, et al. Effects of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome:a randomised study. Current Medical Research and Opinion, 2006, 22(5): 873-883.
23.	Vega GL, Ma PT, Cater NB, et al. Effects of Adding Fenofibrate (200 mg/day) to Simvastatin (10 mg/ day) in Patients With Combined Hyperlipidemia and Metabolic Syndrome. Am J Cardiol, 2003, 91(8): 956-960.
24.	Vega GL, Cater NB, Hadizadeh DR 3rd, et al. Free fatty acid metabolism during fenofibrate treatment of the metabolism syndrome. Clin Pharmacol Ther, 2003, 74(3): 236-244.
25.	Stalenhoef AF, Ballantyne CM, Sarti C, et al. A Comparative study with rosuvastatin in subjects with METabolic Syndrome: results of the COMETS study. European Heart Journal, 2005, 26(24): 2664-2672.
26.	Koh WK, Han SH, Ahn JY, et al. Beneficial Effects of Fenofibrate to Improve Endothelial Dysfunction and Raise Adiponectin Levels in Patients With Primary Hypertriglyceridemia. Diabetes Care, 2005, 28(6): 1419-1424.
27.	Ballantyne CM, Blazing MA, Hunninghake DB, et al. Effect on highdensity lipoprotein cholesterol of maximum dose simvastatin and atorvastatin in patients with hypercholesterolemia: Results of the comparative HDL efficacy and safety study (CHESS). Am Heart J, 2003, 146(5): 862-869.
28.	Davidson MH, Bays H, Rhyne J, et al. Efficacy and Safety Profile of Fenofibrate-Coated Microgranules 130mg, With and Without Food, in Patients with Hypertriglyceridemia and the Metabolic Syndrome: An 8-Week, Randomized, Double -Blind, Placebo-ControlledStudy. Clinical Therapeutics J, 2005, 27(6): 715-727.
29.	Trøseid M, Lappegård KT, Mollnes TE, et al. Changes in serum levels of E-selectin correlate to improved glycaemic control and reduced obesity in subjects with the metabolic syndrome. Scand J Clin Lab Invest, 2005, 65(4): 283-290.
30.	Hanley AJ, Williams K, Gonzalez C, et al. The San Antonio Heart Study, the Mexico City Diabetes Study, the Insulin Resistance Atherosclerosis Study: Prediction of type 2 diabetes using simple measures of insulin resistance: combined results from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study. Diabetes, 2003, 52(2): 463-469.

1. systemic inflammation: reversal with bezafibrate therapy in a randomized controlled trial. Am J Med, 2002, 112(4): 275-280.
2. Rizos E, Kostoula A, Elisaf M, et al. Effect of ciprofibrate on C-reactive protein and fibrinogen levels. Angiology, 2002, 53(3): 273-277.
3. Avogaro A, Miola M, Favaro A, et al. Gemfibrozil improves insulin sensitivity and flow- mediated vasodilatation in type 2 diabetic patients. Eur J Clin Invest, 2001, 31(7): 603-609.
4. Jonkers IJ, Mohrschladt MF, Weterndorp RG, et al. Severe hypertriglyceridemia with insulin resistance is associated with.
5. Tenenbaum A, Motro M, Fisman EZ, et al. Peroxisome proliferatoractivated receptors ligand bezafibrate for prevention type 2 diabetes mellitus in patients with coronary artery disease. Circulation, 2004, 109(18): 2197-2202.
6. Fruchart JC, Staels B, Duriez P. The role of fibric acids in atherosclerosis. Curr Atherosler Rep, 2001, (3): 83-92.
7. Wang TD, Chen WJ, Lin JW, et al. Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles. Atheroslerosis, 2003, 170(2): 315-323.
8. Rubins HB, Rubins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Trail Study Group. N Engl J Med, 1999, 341(6): 410-418.
9. Anonymous. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate infarction Prevention( BIP) study. Circulation, 2000, 102(1): 21-27.
10. Diabetes Atherosclerosis Intervention Study Group. Lancet, 2001, 357: 90-96.
11. The FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet, 2005, 366(9500): 1849-1861.
12. Heart Protection Study Collaborative Group. MRC／BHF Heart Protection Study of cholesterol lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet, 2003, 361(9374): 2005-2016.
13. Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertension patients who have average or lower-than-average cholesterol concentration, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet, 2003, 361(9364): l149-1158.
14. Canner PL, Furberg CD, Terrin ML, et al. Benefits of niacin by glycemic status in patients with healed myocardial infarction (from the Coronary Drug Project). Am J Cardiol, 2005, 95(2): 254-257.
15. Alberti KGMM, Zimmet PZ, WHO Consultation. Definition, diagnosis and classification of diabetes mellitus and itscomplications.Part 1:diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med, 1998, (15): 539-553.
16. Expert Panel on Detection, Evaluation, and Treatment of High Blood cholesterol in Adults (Adult treatment Panel Ⅲ). Executive summary of the third report of the National Cholesteral Eduation Program (NECP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. J Am Med Assoc, 2001, 285(19): 2486-2497.
17. Barclay L. Medscape Medical News. New definition of the metabolic syndrome: a newsmaker interview with Sir George Alberti, MA, DPhil, BMBCh. Available at: http://www.medscape.com/viewarticle/504382 Accessed July 8, 2005.
18. 吴泰相, 刘关键. 隐蔽分组（分配隐藏）和盲法的概念、实施与报告. 中国循证医学杂志, 2007, 7(3): 222-225.
19. Filippatos TD, Kiortsis DN, Liberopoulos EN, et al. Effects of orlistat, micronised fenofibrate and their combination on metabolic parameters in overweinght and obese patients with the metabolic syndrome:the FenOrli study. Current Medical Research and Opinion, 2005, 21 (12): 1997-2006.
20. Filippatos TD, Gazi IF, Liberopoulos EN, et al. The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic syndrome. Atherosclerosis, 2007, 193(2): 428-437.
21. Athyros VG, Mikhailidis DP, Papage-orgiou AA, et al. Targeting vascular risk in patients with metabolic syndrome but without diabetes. Metabolism Clinical and Experimental, 2005, 54(8): 1065-1074.
22. Athyros VG, Mikhailidis DP, Didan-gelos TP, et al. Effects of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome:a randomised study. Current Medical Research and Opinion, 2006, 22(5): 873-883.
23. Vega GL, Ma PT, Cater NB, et al. Effects of Adding Fenofibrate (200 mg/day) to Simvastatin (10 mg/ day) in Patients With Combined Hyperlipidemia and Metabolic Syndrome. Am J Cardiol, 2003, 91(8): 956-960.
24. Vega GL, Cater NB, Hadizadeh DR 3rd, et al. Free fatty acid metabolism during fenofibrate treatment of the metabolism syndrome. Clin Pharmacol Ther, 2003, 74(3): 236-244.
25. Stalenhoef AF, Ballantyne CM, Sarti C, et al. A Comparative study with rosuvastatin in subjects with METabolic Syndrome: results of the COMETS study. European Heart Journal, 2005, 26(24): 2664-2672.
26. Koh WK, Han SH, Ahn JY, et al. Beneficial Effects of Fenofibrate to Improve Endothelial Dysfunction and Raise Adiponectin Levels in Patients With Primary Hypertriglyceridemia. Diabetes Care, 2005, 28(6): 1419-1424.
27. Ballantyne CM, Blazing MA, Hunninghake DB, et al. Effect on highdensity lipoprotein cholesterol of maximum dose simvastatin and atorvastatin in patients with hypercholesterolemia: Results of the comparative HDL efficacy and safety study (CHESS). Am Heart J, 2003, 146(5): 862-869.
28. Davidson MH, Bays H, Rhyne J, et al. Efficacy and Safety Profile of Fenofibrate-Coated Microgranules 130mg, With and Without Food, in Patients with Hypertriglyceridemia and the Metabolic Syndrome: An 8-Week, Randomized, Double -Blind, Placebo-ControlledStudy. Clinical Therapeutics J, 2005, 27(6): 715-727.
29. Trøseid M, Lappegård KT, Mollnes TE, et al. Changes in serum levels of E-selectin correlate to improved glycaemic control and reduced obesity in subjects with the metabolic syndrome. Scand J Clin Lab Invest, 2005, 65(4): 283-290.
30. Hanley AJ, Williams K, Gonzalez C, et al. The San Antonio Heart Study, the Mexico City Diabetes Study, the Insulin Resistance Atherosclerosis Study: Prediction of type 2 diabetes using simple measures of insulin resistance: combined results from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study. Diabetes, 2003, 52(2): 463-469.

《中国循证医学杂志》

调血脂药治疗代谢综合征的系统评价

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《中国循证医学杂志》

调血脂药治疗代谢综合征的系统评价

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