調血脂藥治療代謝綜合征的系統評價_《中國循證醫學雜志》

作者：

勾忠平 ¹ ,  李秀鈞 ² , 吳泰相 ³

1. 四川大學華西醫院GCP中心（成都 610041）2. 四川大學華西醫院內分泌科（成都 610041）3. 四川大學華西醫院中國循證醫學中心（成都 610041）;

關鍵詞：

代謝綜合征調血脂藥他汀類貝特類系統評價隨機對照試驗

DOI：

10.7507/1672-2531.20090067

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目的　系統評價調血脂藥治療代謝綜合征（MS）的有效性和安全性。
方法　計算機檢索Cochrane 圖書館（2007 年第4 期）、MEDLINE（1966 ～ 2007）、EMbase（1984 ～ 2007）、中國生物醫學文獻數據庫（1978 ～ 2007）、中國學術期刊全文數據庫（1979 ～ 2007）和中文科技期刊全文數據庫（1989 ～2007），手工檢索《中華內分泌代謝雜志》等相關雜志，納入調血脂藥治療MS 的隨機或半隨機對照試驗，按Cochrane 標準評價納入研究質量，對同質研究采用RevMan 4.2 軟件進行Meta 分析，反之則只進行描述性的定性分析。
結果　共納入9 個隨機對照試驗，合計1 420 例MS 患者。Meta 分析結果顯示：羅蘇伐他汀與阿托伐他汀比較，兩組對穩態模型胰島素抵抗指數（HOMA index）、FPG、HbA1C 無改善，羅蘇伐他汀組升高HDL-c 的療效優于阿托伐他汀組，對TG 的影響兩組差異無統計學意義；辛伐他汀與阿托伐他汀比較，辛伐他汀組升高HDL-c 的療效優于阿托伐他汀組，辛伐他汀組降低TG 的療效差于阿托伐他汀組；普伐他汀與對照組比較，兩組對腰圍（WC）、體重指數（BMI）、FPG、HbA1C 無影響。有2個研究為非諾貝特（200 mg）與安慰劑比較，1 個研究顯示對HOMA index 的影響兩組差異無統計學意義，另1 個研究顯示非諾貝特組對QUICKI 的改善優于安慰劑組；對BMI、FPG［WMD= 0.0，95%CI（– 0.15，0.15）］的影響，兩組差異無統計學意義；非諾貝特組對TG［WMD= – 1.77，95%CI（– 2.21，– 1.33）］、HDL-c［WMD= 6.62，95%CI（2.07，11.17）］的改善優于安慰劑組。1 個研究為非諾貝特（130 mg，與進食同服/ 不與進食同服）與安慰劑比較，對SBP、WC 的影響差異無統計學意義；非諾貝特組對HDL-c、TG 的改善優于安慰劑組（P lt;0.001）。阿托伐他汀、非諾貝特、阿托伐他汀+ 非諾貝特比較，對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 的影響3 組差異無統計學意義；阿托伐他汀組、阿托伐他汀+ 非諾貝特組降低SBP/ DBP 的療效優于非諾貝特組；非諾貝特+ 阿托伐他汀組對HDL-c、TG 的改善優于阿托伐他汀組。辛伐他汀、辛伐他汀+ 非諾貝特比較，對FPG 的影響兩組差異無統計學意義，辛伐他汀+ 非諾貝特組對HDL-c、TG 的改善優于辛伐他汀組。奧利司他+ 非諾貝特與奧利司他比較，對降低MS 患者比率、SBP/DBP、BMI、WC、FPG、HOMA index 的療效差異無統計學意義；奧利司他+ 非諾貝特組降低TG 的療效優于奧利司他組（P lt;0.05）；對HDL-c 的影響兩組差異無統計學意義。9 個納入研究均無對心血管事件和糖尿病發生率結局指標的報道。有6 個研究報道了不良反應，結果顯示調脂藥耐受性良好，多數不良反應為輕至中度。
結論　本次系統評價所納入的9 個研究均缺乏對遠期結局指標的觀測，近期觀察結果表明調脂藥（他汀類、貝特類）對MS 患者血脂（TG、HDL-c）改善有積極的效果，但對血壓、胰島素敏感性的療效不確定；目前未發現對血糖、肥胖指標有改善作用。由于上述結論基本來自單個研究，樣本量小，納入研究總體質量不高，因此對待結論需謹慎。目前尚無足夠的證據證明哪種藥物更有效，非常有必要開展更多高質量、大樣本、長期隨訪的RCT，以提供更可靠的證據。

引用本文： 勾忠平,李秀鈞,吳泰相. 調血脂藥治療代謝綜合征的系統評價. 中國循證醫學雜志, 2009, 09(3): 355-364. doi: 10.7507/1672-2531.20090067 復制

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.	吳泰相, 劉關鍵. 隱蔽分組（分配隱藏）和盲法的概念、實施與報告. 中國循證醫學雜志, 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.	Tr?seid M, Lappeg?rd 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. 吳泰相, 劉關鍵. 隱蔽分組（分配隱藏）和盲法的概念、實施與報告. 中國循證醫學雜志, 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. Tr?seid M, Lappeg?rd 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.

《中國循證醫學雜志》

調血脂藥治療代謝綜合征的系統評價

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