Efficacy of Coenzyme Q10 as Adjuvant Therapy in Heart Failure: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 BAYi-jie ¹ , YANGMiao ¹ , SUNYi ² , LIZe ³ , CHENGGang ⁴ , ZHANGShuo ¹ ,  ZOUMei-juan ⁴

1. School of Life Science and Biological Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;
2. Department of Cardiology, General Hospital of Shenyang Military Region, Shenyang 110016, China;
3. Department of Pharmacy, General Hospital of Shenyang Military Region, Shenyang 110016, China;
4. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;

Corresponding author：

ZOUMei-juan, Email: zoumeijuan@163.com

Keywords：

Coenzyme Q10; Heart failure; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.20160049

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To systematically review the efficacy of coenzyme Q10 as adjuvant therapy for patients with heart failure. Methods Databases including PubMed, The Cochrane Library (Issue 7, 2015), EMbase, CBM, CNKI, WanFang Data and VIP were searched to collect randomized controlled trials (RCTs) about coenzyme Q10 in the treatment of heart failure from inception to June 2015. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software. Results A total of 24 RCTs involving 2883 patients were included. The results of meta-analysis showed that:compared with the control group, the coenzyme Q10 group had the lower mortality (RR=0.62, 95%CI 0.47 to 0.83, P=0.001), higher eject fraction (EF) level (MD=3.81, 95%CI 1.22 to 6.40, P=0.004), lower NYHA cardiac function classification (MD=-0.31, 95%CI -0.35 to -0.26), P<0.00001), and higher exercise tolerance (SMD=0.70, 95%CI 0.31 to 1.09, P=0.0005). Conclusion Current evidence shows that, coenzyme Q10 can reduce mortality, NYHA cardiac function classification and improve EF and exercise tolerance in patients with heart failure. Due to the limited quality of included studies, the above conclusion still needs to be verified by more high quality studies.

Citation： BAYi-jie, YANGMiao, SUNYi, LIZe, CHENGGang, ZHANGShuo, ZOUMei-juan. Efficacy of Coenzyme Q10 as Adjuvant Therapy in Heart Failure: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2016, 16(3): 311-318. doi: 10.7507/1672-2531.20160049 Copy

1.	中国医学会心血管病学分会. 中国心力衰竭诊断和治疗指南2014. 中国心血管病杂志, 2014, 42(2):98-122.
2.	Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol, 2013, 62(16):e147-239.
3.	Callender T, Woodward M, Roth G, et al. Heart failure care in low-and middle-income countries:a systematic review and meta-analysis. PLoS Med, 2014, 11(8):e1001699.
4.	Roger VL, Weston SA, Redfield MM, et al. Trends in heart failure incidence and survival in a community-based population. JAMA, 2004, 292(3):344-350.
5.	Levy D, Kenchaiah S, Larson MG, et al. Long-term trends in the incidence of and survival with heart failure. N Engl J Med, 2002, 347(18):1397-1402.
6.	吴胜楠. 顽固性心力衰竭的治疗. 中国实用内科杂志, 2000, 20(5):268-270.
7.	Folkers K, Vadhanavikit S, Mortensen SA, et al. Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc Natl Acad Sci USA, 1985, 82(3):901-904.
8.	Molyneux SL, Florkowski CM, George PM, et al. Coenzyme Q10:an independent predictor of mortality in chronic heart failure. J Am Coll Cardiol, 2008, 52(18):1435-1441.
9.	邓可刚. 循证医学证据的检索步骤与检索系统的选择. 中国循证医学杂志, 2004, 4(9):634-637.
10.	Higgins J, Altman D, Sterne J, et al. Chapter 8:Assessing risk of bias in included studies. In:Higgins JPT, Green S In:Sterne J, editor. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). Available at:http://www.cochranehandbook.org:TheCochraneCollaboration;2011.
11.	Adarsh K, Kaur H, Mohan V, et al. Coenzyme Q10 (CoQ10) in isolated diastolic heart failure in hypertrophic cardiomyopathy (HCM). Biofactors, 2008, 32(1-4):145-149.
12.	Belardinelli R, Mucaj A, Lacalaprice F, et al. Coenzyme Q(10) and exercise training in chronic heart failure. Eur Heart J, 2006, 27(22):2675-2681.
13.	Hofman-Bang C, Rehnqvist N, Swedberg K, et al. Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. The Q10 Study Group. J Card Fail, 1995, 1(2):101-107.
14.	Keogh A, Fenton S, Leslie C, et al. Randomised double-blind, placebo-controlled trial of coenzyme Q(10) therapy in class Ⅱ and Ⅲ systolic heart failure. Heart Lung Circ, 2003, 12(3):135-141.
15.	Khatta M, Alexander BS, Krichten CM, et al. The effect of coenzyme Q(10) in patients with congestive heart failure. Ann Intern Med, 2000, 132(8):636-640.
16.	Morisco C, Trimarco B, Condorelli M, et al. Effect of coenzyme Q10 therapy in patients with congestive heart failure:a long-term multicenter randomized study. Clin Investig, 1993, 71(8 Suppl):S134-136.
17.	Morisco C, Nappi A, Argenziano L, et al. Noninvasive evaluation of cardiac hemodynamics during exercise in patients with chronic heart failure:Effects of short-term coenzyme Q10 treatment. Mol Aspects Med, 1994, 15(Suppl):S155-S163.
18.	Mortensen SA, Rosenfeldt F, Kumar A, et al. The effect of coenzyme Q(10) on morbidity and mortality in chronic heart failure:Results from Q-SYMBIO:A randomized double-blind trial. JACC Heart Fail, 2014, 2(6):641-649.
19.	Munkholm H, Hansen HHT, Rasmussen K, et al. Coenzyme Q(10) treatment in serious heart failure. Biofactors, 1999, 9(24):285-289.
20.	Permanetter B, Rossy W, Klein G, et al. Ubiquinone (coenzyme Q10) in the long-term treatment of idiopathic dilated cardiomyopathy. Eur Heart J, 1992, 13(11):1528-1533.
21.	Pourmoghaddas M, Rabbani M, Shahabi J, et al. Combination of atorvastatin/coenzyme Q10 as adjunctive treatment in congestive heart failure:A double-blind randomized placebo-controlled clinical trial. ARYA Atherosclerosis, 2014,10(1):1-5.
22.	Zhao Q, Kebbati AH, Zhang Y, et al. Effect of coenzyme Q10 on the incidence of atrial fibrillation in patients with heart failure. J Investig Med, 2015, 63(5):735-739.
23.	Watson PS, Scalia GM, Galbraith A, et al. Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure. J Am Coll Cardiol, 1999, 33(6):1549-1552.
24.	毕君富. 辅酶Q10治疗扩张型心肌病心力衰竭患者的疗效观察. 实用心脑肺血管病杂志, 2012, 20(11):1813-1814.
25.	冯泽勇, 白涛峰, 张留峰. 辅酶Q10联合常规治疗心衰206例临床观察. 河北医学, 2010, 16(10):1184-1187.
26.	龙云群. 阿托伐他汀联合辅酶Q10对慢性心衰患者心功能的影响. 中国医药导刊, 2011, 13(4):638-640.
27.	欧志福. 小剂量辛伐他汀联合辅酶Q10治疗慢性心衰的临床研究. 国际医药卫生导报. 2012,18(22):3278-3280.
28.	彭文近, 王怀祯, 刘迎午. 阿托伐他汀联合辅酶Q10治疗心力衰竭106例疗效观察. 2009年第五届海河之滨心脏病学会议. 天津:中华医学会/天津市医学会, 2009:243-245.
29.	吴炎. 辅酶Q10对高龄慢性心功能不全的疗效及安全性分析. 中国老年保健医学, 2014, 12(3):42-43.
30.	邢红云, 玛丽亚, 宋美红. 辅酶Q10治疗原发性扩张型心肌病48例临床疗效观察. 新疆医学, 1999,29(3):155-157.
31.	杨栋梁. 辅酶Q10降低慢性心力衰竭患者发生主要不良心血管事件的临床观察. 临床合理用药杂志, 2013, 6(30):19.
32.	姚秀萍, 李华, 高永艳. CoQ10治疗慢性心功能不全:一项随机双盲、对照研究. 中华老年多器官疾病杂志, 2012, 11(6):435-437.
33.	赵红梅, 徐明. 辛伐他汀及联用辅酶Q10对扩张型心肌病的疗效观察. 陕西医学杂志, 2008, 37(4):499-501.
34.	赵晖, 于建华. 慢性心衰患者阿托伐他汀联合辅酶Q10治疗后心功能及血清炎性指标的变化. 山东医药, 2010, 50(13):90-91.
35.	Cohn J, Rector T. Prognosis of congestive heart failure and predictors of mortality. Am J Cardiol, 1988, 62(2):25A-30A.
36.	Gradman A, Deedwania P, Cody R, et al. Predictors of total mortality and sudden death in mild to moderate heart failure, Captopril-Dixogin Study Group. J Am Coll Cardiol, 1989, 14(3):564-570.
37.	Crane F. Biochemical functions of coenzyme Q10. J Am Coll Nutr, 2001, 20(6):591-598.
38.	Littarru G. Location and function of coenzyme Q in the respiratory chain. Rome:Casa Editrice Scientifica Internazionale. 1994:14-22.
39.	Van den Heuvel A, Van Veldhuisen D, van der Wall E, et al. Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol, 2000, 35(1):19-28.
40.	聂晓莉, 曾祥鸿, 周世炳. 心血管疾病与超氧化物歧化酶和过氧化脂质关系的探讨. 临床心血管病杂志, 1995, 11(5):299-300.
41.	Ferrari R, Guardigli G, Mele D, et al. Oxidative stress during myocardial ischaemia and heart failure. Curr Pharm Des, 2004, 10(14):1699-1711.
42.	Hodgson J, Watts G. Can coenzyme Q10 improve vascular function and blood pressure? Potential or effective therapeutic in vascular oxidative stress. Biofactors, 2003, 18(1-4):129-136.
43.	McCarty M. Caoenzyme Q versus hypertension:does CoQ decrease endothelial superoxide generation? Med Hypoth, 1999, 53(4):300-304.
44.	Forsmark-Andrée P, Lee C, Dallner G, et al. Lipid peroxidation and changes in the ubiquinone content and the respiratory chain enzymes of submitochondrial particles. Free Radic Biol Med, 1997, 22(3):391-400.
45.	Pacher P, Schulz R, Liaudet L, et al. Nitrosative stress and pharmacological modulation of heart failure. Trends Pharmacol Sci, 2005, 26(6):302-310.
46.	Rosenfeldt F, Marasco S, Lyon W, et al. Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue. J Thorac Cardiovasc Surg, 2005, 129(1):25-32.
47.	Franklin R, Deborah H, Salvatore P, et al. Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure. BioFactors, 2003:91-100.
48.	Fotino AD, Thompson-Paul AM, Bazzano LA, et al. Effect of coenzyme Q(1)(0) supplementation on heart failure:a meta-analysis. Am J Clin Nutr, 2013, 97(2):268-275.
49.	Sojaa AM, Mortensenb SA. Treatment of Congestive Heart Failure with Coenzyme Q10 Illuminated by Meta-analyses of Clinical Trials. Molec Aspects Med, 1997, 18(Suppl):S159-168.
50.	Sander S, Coleman CI, Patel AA, et al. The impact of coenzyme Q10 on systolic function in patients with chronic heart failure. J Card Fail, 2006, 12(6):464-472.
51.	Madmani M, Yusuf Solaiman A, Tamr Agha K, et al. Coenzyme Q10 for heart failure (Review). The Cochrane Library. 2014.
52.	Crane F. Discovery of ubiquinone (coenzyme Q) and an overview of function. Mitochondrion, 2007, 7(Suppl):S2-7.
53.	Bentinger, M Brismar, K Dallner G, et al. The antioxidant role of coenzyme Q. Mitochondrion, 2007, 7(Suppl):41-50.
54.	Rustin P, Munnich A, Rötig A, et al. Mitochondrial respiratory chain dysfunction caused by coenzyme Q deficiency. Meth Enzymol, 2004, 382:81-88.

1. 中国医学会心血管病学分会. 中国心力衰竭诊断和治疗指南2014. 中国心血管病杂志, 2014, 42(2):98-122.
2. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol, 2013, 62(16):e147-239.
3. Callender T, Woodward M, Roth G, et al. Heart failure care in low-and middle-income countries:a systematic review and meta-analysis. PLoS Med, 2014, 11(8):e1001699.
4. Roger VL, Weston SA, Redfield MM, et al. Trends in heart failure incidence and survival in a community-based population. JAMA, 2004, 292(3):344-350.
5. Levy D, Kenchaiah S, Larson MG, et al. Long-term trends in the incidence of and survival with heart failure. N Engl J Med, 2002, 347(18):1397-1402.
6. 吴胜楠. 顽固性心力衰竭的治疗. 中国实用内科杂志, 2000, 20(5):268-270.
7. Folkers K, Vadhanavikit S, Mortensen SA, et al. Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc Natl Acad Sci USA, 1985, 82(3):901-904.
8. Molyneux SL, Florkowski CM, George PM, et al. Coenzyme Q10:an independent predictor of mortality in chronic heart failure. J Am Coll Cardiol, 2008, 52(18):1435-1441.
9. 邓可刚. 循证医学证据的检索步骤与检索系统的选择. 中国循证医学杂志, 2004, 4(9):634-637.
10. Higgins J, Altman D, Sterne J, et al. Chapter 8:Assessing risk of bias in included studies. In:Higgins JPT, Green S In:Sterne J, editor. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). Available at:http://www.cochranehandbook.org:TheCochraneCollaboration;2011.
11. Adarsh K, Kaur H, Mohan V, et al. Coenzyme Q10 (CoQ10) in isolated diastolic heart failure in hypertrophic cardiomyopathy (HCM). Biofactors, 2008, 32(1-4):145-149.
12. Belardinelli R, Mucaj A, Lacalaprice F, et al. Coenzyme Q(10) and exercise training in chronic heart failure. Eur Heart J, 2006, 27(22):2675-2681.
13. Hofman-Bang C, Rehnqvist N, Swedberg K, et al. Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. The Q10 Study Group. J Card Fail, 1995, 1(2):101-107.
14. Keogh A, Fenton S, Leslie C, et al. Randomised double-blind, placebo-controlled trial of coenzyme Q(10) therapy in class Ⅱ and Ⅲ systolic heart failure. Heart Lung Circ, 2003, 12(3):135-141.
15. Khatta M, Alexander BS, Krichten CM, et al. The effect of coenzyme Q(10) in patients with congestive heart failure. Ann Intern Med, 2000, 132(8):636-640.
16. Morisco C, Trimarco B, Condorelli M, et al. Effect of coenzyme Q10 therapy in patients with congestive heart failure:a long-term multicenter randomized study. Clin Investig, 1993, 71(8 Suppl):S134-136.
17. Morisco C, Nappi A, Argenziano L, et al. Noninvasive evaluation of cardiac hemodynamics during exercise in patients with chronic heart failure:Effects of short-term coenzyme Q10 treatment. Mol Aspects Med, 1994, 15(Suppl):S155-S163.
18. Mortensen SA, Rosenfeldt F, Kumar A, et al. The effect of coenzyme Q(10) on morbidity and mortality in chronic heart failure:Results from Q-SYMBIO:A randomized double-blind trial. JACC Heart Fail, 2014, 2(6):641-649.
19. Munkholm H, Hansen HHT, Rasmussen K, et al. Coenzyme Q(10) treatment in serious heart failure. Biofactors, 1999, 9(24):285-289.
20. Permanetter B, Rossy W, Klein G, et al. Ubiquinone (coenzyme Q10) in the long-term treatment of idiopathic dilated cardiomyopathy. Eur Heart J, 1992, 13(11):1528-1533.
21. Pourmoghaddas M, Rabbani M, Shahabi J, et al. Combination of atorvastatin/coenzyme Q10 as adjunctive treatment in congestive heart failure:A double-blind randomized placebo-controlled clinical trial. ARYA Atherosclerosis, 2014,10(1):1-5.
22. Zhao Q, Kebbati AH, Zhang Y, et al. Effect of coenzyme Q10 on the incidence of atrial fibrillation in patients with heart failure. J Investig Med, 2015, 63(5):735-739.
23. Watson PS, Scalia GM, Galbraith A, et al. Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure. J Am Coll Cardiol, 1999, 33(6):1549-1552.
24. 毕君富. 辅酶Q10治疗扩张型心肌病心力衰竭患者的疗效观察. 实用心脑肺血管病杂志, 2012, 20(11):1813-1814.
25. 冯泽勇, 白涛峰, 张留峰. 辅酶Q10联合常规治疗心衰206例临床观察. 河北医学, 2010, 16(10):1184-1187.
26. 龙云群. 阿托伐他汀联合辅酶Q10对慢性心衰患者心功能的影响. 中国医药导刊, 2011, 13(4):638-640.
27. 欧志福. 小剂量辛伐他汀联合辅酶Q10治疗慢性心衰的临床研究. 国际医药卫生导报. 2012,18(22):3278-3280.
28. 彭文近, 王怀祯, 刘迎午. 阿托伐他汀联合辅酶Q10治疗心力衰竭106例疗效观察. 2009年第五届海河之滨心脏病学会议. 天津:中华医学会/天津市医学会, 2009:243-245.
29. 吴炎. 辅酶Q10对高龄慢性心功能不全的疗效及安全性分析. 中国老年保健医学, 2014, 12(3):42-43.
30. 邢红云, 玛丽亚, 宋美红. 辅酶Q10治疗原发性扩张型心肌病48例临床疗效观察. 新疆医学, 1999,29(3):155-157.
31. 杨栋梁. 辅酶Q10降低慢性心力衰竭患者发生主要不良心血管事件的临床观察. 临床合理用药杂志, 2013, 6(30):19.
32. 姚秀萍, 李华, 高永艳. CoQ10治疗慢性心功能不全:一项随机双盲、对照研究. 中华老年多器官疾病杂志, 2012, 11(6):435-437.
33. 赵红梅, 徐明. 辛伐他汀及联用辅酶Q10对扩张型心肌病的疗效观察. 陕西医学杂志, 2008, 37(4):499-501.
34. 赵晖, 于建华. 慢性心衰患者阿托伐他汀联合辅酶Q10治疗后心功能及血清炎性指标的变化. 山东医药, 2010, 50(13):90-91.
35. Cohn J, Rector T. Prognosis of congestive heart failure and predictors of mortality. Am J Cardiol, 1988, 62(2):25A-30A.
36. Gradman A, Deedwania P, Cody R, et al. Predictors of total mortality and sudden death in mild to moderate heart failure, Captopril-Dixogin Study Group. J Am Coll Cardiol, 1989, 14(3):564-570.
37. Crane F. Biochemical functions of coenzyme Q10. J Am Coll Nutr, 2001, 20(6):591-598.
38. Littarru G. Location and function of coenzyme Q in the respiratory chain. Rome:Casa Editrice Scientifica Internazionale. 1994:14-22.
39. Van den Heuvel A, Van Veldhuisen D, van der Wall E, et al. Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol, 2000, 35(1):19-28.
40. 聂晓莉, 曾祥鸿, 周世炳. 心血管疾病与超氧化物歧化酶和过氧化脂质关系的探讨. 临床心血管病杂志, 1995, 11(5):299-300.
41. Ferrari R, Guardigli G, Mele D, et al. Oxidative stress during myocardial ischaemia and heart failure. Curr Pharm Des, 2004, 10(14):1699-1711.
42. Hodgson J, Watts G. Can coenzyme Q10 improve vascular function and blood pressure? Potential or effective therapeutic in vascular oxidative stress. Biofactors, 2003, 18(1-4):129-136.
43. McCarty M. Caoenzyme Q versus hypertension:does CoQ decrease endothelial superoxide generation? Med Hypoth, 1999, 53(4):300-304.
44. Forsmark-Andrée P, Lee C, Dallner G, et al. Lipid peroxidation and changes in the ubiquinone content and the respiratory chain enzymes of submitochondrial particles. Free Radic Biol Med, 1997, 22(3):391-400.
45. Pacher P, Schulz R, Liaudet L, et al. Nitrosative stress and pharmacological modulation of heart failure. Trends Pharmacol Sci, 2005, 26(6):302-310.
46. Rosenfeldt F, Marasco S, Lyon W, et al. Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue. J Thorac Cardiovasc Surg, 2005, 129(1):25-32.
47. Franklin R, Deborah H, Salvatore P, et al. Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure. BioFactors, 2003:91-100.
48. Fotino AD, Thompson-Paul AM, Bazzano LA, et al. Effect of coenzyme Q(1)(0) supplementation on heart failure:a meta-analysis. Am J Clin Nutr, 2013, 97(2):268-275.
49. Sojaa AM, Mortensenb SA. Treatment of Congestive Heart Failure with Coenzyme Q10 Illuminated by Meta-analyses of Clinical Trials. Molec Aspects Med, 1997, 18(Suppl):S159-168.
50. Sander S, Coleman CI, Patel AA, et al. The impact of coenzyme Q10 on systolic function in patients with chronic heart failure. J Card Fail, 2006, 12(6):464-472.
51. Madmani M, Yusuf Solaiman A, Tamr Agha K, et al. Coenzyme Q10 for heart failure (Review). The Cochrane Library. 2014.
52. Crane F. Discovery of ubiquinone (coenzyme Q) and an overview of function. Mitochondrion, 2007, 7(Suppl):S2-7.
53. Bentinger, M Brismar, K Dallner G, et al. The antioxidant role of coenzyme Q. Mitochondrion, 2007, 7(Suppl):41-50.
54. Rustin P, Munnich A, Rötig A, et al. Mitochondrial respiratory chain dysfunction caused by coenzyme Q deficiency. Meth Enzymol, 2004, 382:81-88.

Chinese Journal of Evidence-Based Medicine

Efficacy of Coenzyme Q10 as Adjuvant Therapy in Heart Failure: A Meta-analysis

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