Español Evidence for the management of myopathies associated with statin with coenzyme Q10
DOI:
https://doi.org/10.30827/ars.v63i1.21930Keywords:
statin associated muscle symptoms; HMG-CoA reductase inhibitors; coenzyme Q10Abstract
Introduction: The incidence of fatal cardiovascular events is very high and statin treatment is vital to reduce this risk in many patients, however, its adverse effects on skeletal muscle make it difficult to adhere or continue it. Coenzyme Q10 supplementation has been proposed to reverse myalgia associated with the use of statins. The clinical trials carried out in the last 10 years obtained conflicting results.
The aim of the present work is to review the evidence on the efficacy of the use of coenzyme Q10 supplements in mitigating myopathies caused by statins.
Methodology: A systematic review of the published literature until July 2020 was undertaken. The searched databases were MEDLINE and SCOPUS. Institutions such as the Agencia Española del Medicamento y productos Sanitarios (AEMPS), European Medicines Agency (EMA) and Food and Drug Administration were also consulted.
Results: The etiology of statin-associated myalgias remains unknown, and the evidence found in clinical trials and meta-analysis drew disparate conclusions. The European Medicine Agency (EMA) only considers the use of supplements in primary coenzyme Q10 deficiency syndrome, while in the United Kingdom the National Institute for Health and Care Excellence (NICE) and the National Institute of Health (NIH) do not recommend the use of these supplements to treat myalgias associated with the use of statins.
Conclusions: The set of studies analyzed did not obtain unanimous evidence to be able to reliably recommend this use of coenzyme Q10 supplements. Better designed studies that provide reproducibility and robustness to future clinical trials are needed.
Downloads
References
Instituto Nacional de Estadística. Defunciones por causas (lista reducida) por sexo y grupos de edad (7947) [Internet] 2021 Jun. [cited 2020 Jul 7]. Available from: https://www.ine.es/jaxiT3/Tabla.htm?t=7947
Apostolopoulou M, Corsini A, Roden M. The role of mitochondria in statin-induced myopathy. Eur J Clin Invest. 2015 Jul;45(7):745–54. DOI: 10.1111/eci.12461
Zlatohlavek L, Vrablik M, Grauova B, Motykova E, Ceska R. The effect of coenzyme Q10 in statin myopathy. Neuro Endocrinol Lett. 2012;33 Suppl 2:98–101.
Zaleski AL, Taylor BA, Thompson PD. Coenzyme Q10 as Treatment for Statin-Associated Muscle Symptoms-A Good Idea, but…. Adv Nutr Bethesda Md. 2018 01;9(4):519S-523S. DOI: 10.1093/advances/nmy010
Thompson PD, Panza G, Zaleski A, Taylor B. Statin-Associated Side Effects. J Am Coll Cardiol. 2016 24;67(20):2395–410. DOI: 10.1016/j.jacc.2016.02.071
Taylor BA. Does Coenzyme Q10 Supplementation Mitigate Statin-Associated Muscle Symptoms? Pharmacological and Methodological Considerations. Am J Cardiovasc Drugs Drugs Devices Interv. 2018 Apr;18(2):75–82. DOI: 10.1007/s40256-017-0251-2
Qu H, Guo M, Chai H, Wang W-T, Gao Z-Y, Shi D-Z. Effects of Coenzyme Q10 on Statin-Induced Myopathy: An Updated Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2018 02;7(19):e009835. DOI: 10.1161/JAHA.118.009835
Liu A, Wu Q, Guo J, Ares I, Rodríguez J-L, Martínez-Larrañaga M-R, et al. Statins: Adverse reactions, oxidative stress and metabolic interactions. Pharmacol Ther. 2019;195:54–84. DOI: 10.1016/j.pharmthera.2018.10.004
Parker BA, Gregory SM, Lorson L, Polk D, White CM, Thompson PD. A randomized trial of coenzyme Q10 in patients with statin myopathy: rationale and study design. J Clin Lipidol. 2013 Jun;7(3):187–93. DOI: 10.1016/j.jacl.2013.02.002
Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, et al. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015 May 1;36(17):1012–22. DOI: 10.1093/eurheartj/ehv043
Backes JM, Ruisinger JF, Gibson CA, Moriarty PM. Statin-associated muscle symptoms-Managing the highly intolerant. J Clin Lipidol. 2017 Feb;11(1):24–33. DOI: 10.1016/j.jacl.2017.01.006
Irwin JC, Khalesi S, Fenning AS, Vella RK. The effect of lipophilicity and dose on the frequency of statin-associated muscle symptoms: A systematic review and meta-analysis. Pharmacol Res. 2018 Feb;128:264–73. DOI: 10.1016/j.phrs.2017.09.013
Littlefield N, Beckstrand RL, Luthy KE. Statins’ effect on plasma levels of Coenzyme Q10 and improvement in myopathy with supplementation. J Am Assoc Nurse Pract. 2014 Feb;26(2):85–90. DOI: 10.1002/2327-6924.12046
Harper CR, Jacobson TA. Evidence-based management of statin myopathy. Curr Atheroscler Rep. 2010 Sep;12(5):322–30. DOI: 10.1007 / s11883-010-0120-9
Mas E, Mori TA. Coenzyme Q(10) and statin myalgia: what is the evidence? Curr Atheroscler Rep. 2010 Nov;12(6):407–13. DOI: 10.1007/s11883-010-0134-3
Keller DL. Coenzyme Q10 and statin-induced myopathy--I. Mayo Clin Proc. 2015 Mar;90(3):419–20. DOI: 10.1016/j.mayocp.2015.01.006
Coenzyme Q10 and statin-related myopathy. Drug Ther Bull. 2015 May;53(5):54–6. DOI: 10.1136/dtb.2015.5.0325
Derosa G, D’Angelo A, Maffioli P. Coenzyme q10 liquid supplementation in dyslipidemic subjects with statin-related clinical symptoms: a double-blind, randomized, placebo-controlled study. Drug Des Devel Ther. 2019;13:3647–55. DOI: 10.2147/DDDT.S223153
Dyadyk AI, Kugler TE, Zborowskyy SR, Suliman YV. [Statin-associated muscle symptoms: epidemiology, risk factors, mechanisms and treatment]. Kardiologiia. 2019 Jun 19;59(5S):4–12. DOI: 10.18087/cardio.2522
Agencia Española de Medicamentos y Productos Sanitarios. Ficha Técnica Simvastatina Normon 40 mg comprimidos recubiertos con película EFG [Internet]. [cited 2020 Jul 7]. Available from: https://cima.aemps.es/cima/dochtml/ft/65199/FT_65199.html
Broniarek I, Jarmuszkiewicz W. [Statins and mitochondria]. Postepy Biochem. 2016;62(2):77–84.
Banach M, Serban C, Sahebkar A, Ursoniu S, Rysz J, Muntner P, et al. Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials. Mayo Clin Proc. 2015 Jan;90(1):24–34. DOI: 10.1016/j.mayocp.2014.08.021
Garrido-Maraver J, Cordero MD, Oropesa-Avila M, Vega AF, de la Mata M, Pavon AD, et al. Clinical applications of coenzyme Q10. Front Biosci Landmark Ed. 2014 Jan 1;19:619–33. DOI: 10.2741/4231
Ayer A, Macdonald P, Stocker R. CoQ₁₀ Function and Role in Heart Failure and Ischemic Heart Disease. Annu Rev Nutr. 2015;35:175–213. DOI: 10.1146/annurev-nutr-071714-034258
Klose G. [Statin-associated muscle symptoms]. MMW Fortschr Med. 2018 Jan;160(1):40–3. DOI: 10.1007/s15006-018-0090-3
Braillon A. Coenzyme Q10 and statin-induced myopathy--II. Mayo Clin Proc. 2015 Mar;90(3):420. DOI: 10.1016/j.mayocp.2015.01.005
Bookstaver DA, Burkhalter NA, Hatzigeorgiou C. Effect of coenzyme Q10 supplementation on statin-induced myalgias. Am J Cardiol. 2012 Aug 15;110(4):526–9. DOI: 10.1016/j.amjcard.2012.04.026
Taylor BA, Lorson L, White CM, Thompson PD. A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy. Atherosclerosis. 2015 Feb;238(2):329–35. DOI: 10.1016/j.atherosclerosis.2014.12.016
Tan JT, Barry AR. Coenzyme Q10 for statin-associated myalgia. Am J Health-Syst Pharm AJHP Off J Am Soc Health-Syst Pharm. 2018 15;75(2):15. DOI: 10.2146/ajhp170680
Ahmadi Y, Ghorbanihaghjo A, Naghi-Zadeh M, Yagin NL. Oxidative stress as a possible mechanism of statin-induced myopathy. Inflammopharmacology. 2018 Jun;26(3):667–74. DOI: 10.1007/s10787-018-0469-x
Nielsen ML, Pareek M, Henriksen JE. [Reduced synthesis of coenzyme Q10 may cause statin related myopathy]. Ugeskr Laeger. 2011 Nov 14;173(46):2943–8.
Skarlovnik A, Janić M, Lunder M, Turk M, Šabovič M. Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study. Med Sci Monit Int Med J Exp Clin Res. 2014 Nov 6;20:2183–8. DOI: 10.12659/MSM.890777
Lowe K, Kubra KT, He ZY, Carey K. Vitamin D Supplementation to Treat Statin-Associated Muscle Symptoms: A Review. Sr Care Pharm. 2019 Apr 1;34(4):253–7. DOI: 10.4140/TCP.n.2019.253
Guan ZW, Wu KR, Li R, Yin Y, Li XL, Zhang SF, et al. Pharmacogenetics of statins treatment: Efficacy and safety. J Clin Pharm Ther. 2019 Dec;44(6):858–67. DOI: 10.1111/jcpt.13025
Ramsey LB, Johnson SG, Caudle KE, Haidar CE, Voora D, Wilke RA, et al. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther. 2014 Oct;96(4):423–8. DOI: 10.1038/clpt.2014.125
de Keyser CE, Peters BJM, Becker ML, Visser LE, Uitterlinden AG, Klungel OH, et al. The SLCO1B1 c.521T>C polymorphism is associated with dose decrease or switching during statin therapy in the Rotterdam Study. Pharmacogenet Genomics. 2014 Jan;24(1):43–51. DOI: 10.1097/FPC.0000000000000018
Xiang Q, Chen SQ, Ma LY, Hu K, Zhang Z, Mu GY, et al. Association between SLCO1B1 T521C polymorphism and risk of statin-induced myopathy: a meta-analysis. Pharmacogenomics J. 2018 Dec;18(6):721–9. DOI: 10.1038/s41397-018-0054-0
Liu JE, Liu XY, Chen S, Zhang Y, Cai LY, Yang M, et al. SLCO1B1 521T > C polymorphism associated with rosuvastatin-induced myotoxicity in Chinese coronary artery disease patients: a nested case-control study. Eur J Clin Pharmacol. 2017 Nov;73(11):1409–16. DOI: 10.1007/s00228-017-2318-z
Ramakumari N, Indumathi B, Katkam SK, Kutala VK. Impact of pharmacogenetics on statin-induced myopathy in South-Indian subjects. Indian Heart J. 2018 Dec;70 Suppl 3:S120–5. DOI: 10.1016/j.ihj.2018.07.009
Wilke RA, Moore JH, Burmester JK. Relative impact of CYP3A genotype and concomitant medication on the severity of atorvastatin-induced muscle damage. Pharmacogenet Genomics. 2005 Jun;15(6):415–21. DOI: 10.1097/01213011-200506000-00007
Oh J, Ban MR, Miskie BA, Pollex RL, Hegele RA. Genetic determinants of statin intolerance. Lipids Health Dis. 2007 Mar 21;6:7. DOI: 10.1186/1476-511X-6-7
Puccetti L, Ciani F, Auteri A. Genetic involvement in statins induced myopathy. Preliminary data from an observational case-control study. Atherosclerosis. 2010 Jul;211(1):28–9. DOI: 10.1016/j.atherosclerosis.2010.02.026
Bogsrud MP, Langslet G, Ose L, Arnesen K-E, Sm Stuen MC, Malt UF, et al. No effect of combined coenzyme Q10 and selenium supplementation on atorvastatin-induced myopathy. Scand Cardiovasc J SCJ. 2013 Apr;47(2):80–7. DOI: 10.3109/14017431.2012.756119
European Medicines Agency. Committee for Orphan Medicinal Products. Public summary of opinion on orphan designation: Ubiquinol for the treatment of primary coenzyme Q10 deficiency syndrome (EMA/620954/2016) [Internet]. 2016 Nov [cited 2021 Jul 8]. Available from: https://www.ema.europa.eu/en/documents/orphan-designation/eu/3/16/1765-public-summary-positive-opinion-orphan-designation-ubiquinol-treatment-primary-coenzyme-q10_en.pdf
US Food and Drug Administration. Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act. [Internet]. 2021Jun [cited 2020 Jul 7]. Available from: https://www.fda.gov/media/94164/download
Ruisinger JF, Moriarty PM, Backes JM. Coenzyme Q10 for statin-associated myalgia. Am J Health-Syst Pharm AJHP Off J Am Soc Health-Syst Pharm. 2018 15;75(2):14–5. DOI: 10.2146/ajhp170551
Downloads
Published
How to Cite
Issue
Section
License
The articles, which are published in this journal, are subject to the following terms in relation to the rights of patrimonial or exploitation:
- The authors will keep their copyright and guarantee to the journal the right of first publication of their work, which will be distributed with a Creative Commons BY-NC-SA 4.0 license that allows third parties to reuse the work whenever its author, quote the original source and do not make commercial use of it.
b. The authors may adopt other non-exclusive licensing agreements for the distribution of the published version of the work (e.g., deposit it in an institutional telematic file or publish it in a monographic volume) provided that the original source of its publication is indicated.
c. Authors are allowed and advised to disseminate their work through the Internet (e.g. in institutional repositories or on their website) before and during the submission process, which can produce interesting exchanges and increase citations of the published work. (See The effect of open access).
