Vol 26, No 2 (2019)
Original articles — Clinical cardiology
Published online: 2019-02-20

open access

Page views 6598
Article views/downloads 4523
Get Citation

Connect on Social Media

Connect on Social Media

Effect of coenzyme Q10 in Europeans with chronic heart failure: A sub-group analysis of the Q-SYMBIO randomized double-blind trial

Anne Louise Mortensen, Franklin Rosenfeldt12, Krzysztof J. Filipiak3,
Pubmed: 30835327
Cardiol J 2019;26(2):147-156.

Abstract

Background: Geographical differences in patient characteristics, management and outcomes in heart failure (HF) trials are well recognized. The aim of this study was to assess the consistency of the treat- ment effect of coenzyme Q10 (CoQ10) in the European sub-population of Q-SYMBIO, a randomized double-blind multinational trial of treatment with CoQ10, in addition to standard therapy in chronic HF. 

Methods: Patients with moderate to severe HF were randomized to CoQ10 300 mg daily or placebo in addition to standard therapy. At 3 months the primary short-term endpoints were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro–B type natriuretic peptide. At 2 years the primary long-term endpoint was major adverse cardiovascular events (MACE).

Results: There were no significant changes in short-term endpoints. The primary long-term endpoint of MACE was reached by significantly fewer patients in the CoQ10 group (n = 10, 9%) compared to the placebo group (n = 33, 27%, p = 0.001). The following secondary endpoints were significantly improved in the CoQ10 group compared with the placebo group: all-cause and cardiovascular mortality, NYHA classification and left ventricular ejection fraction (LVEF). In the European sub-population, when compared to the whole group, there was greater adherence to guideline directed therapy and similar results for short- and long-term endpoints. A new finding revealed a significant improvement in LVEF.

Conclusions: The therapeutic efficacy of CoQ10 demonstrated in the Q-SYMBIO study was confirmed in the European sub-population in terms of safely reducing MACE, all-cause mortality, cardiovascular mortality, hospitalization and improvement of symptoms.

Article available in PDF format

View PDF Download PDF file

References

  1. 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.
  2. Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta. 2004; 1660(1-2): 171–199.
  3. Littarru GP, Tiano L. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol. 2007; 37(1): 31–37.
  4. Bhagavan HN, Chopra RK. Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006; 40(5): 445–453.
  5. Kalén A, Appelkvist EL, Dallner G. Age-related changes in the lipid compositions of rat and human tissues. Lipids. 1989; 24(7): 579–584.
  6. Bentinger M, Tekle M, Dallner G. Coenzyme Q--biosynthesis and functions. Biochem Biophys Res Commun. 2010; 396(1): 74–79.
  7. Littarru GP, Tiano L. Clinical aspects of coenzyme Q10: an update. Nutrition. 2010; 26(3): 250–254.
  8. Folkers K, Littarru GP, Ho L, et al. Evidence for a deficiency of coenzyme Q10 in human heart disease. Int Z Vitaminforsch. 1970; 40(3): 380–390.
  9. Folkers K, Vadhanavikit S, Mortensen SA. Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc Natl Acad Sci U S A. 1985; 82(3): 901–904.
  10. Vadhanavikit S, Morishita M, Duff GA, et al. Micro-analysis for coenzyme Q10 in endomyocardial biopsies of cardiac patients and data on bovine and canine hearts. Biochem Biophys Res Commun. 1984; 123(3): 1165–1169.
  11. Sharov VG, Todor AV, Silverman N, et al. Abnormal mitochondrial respiration in failed human myocardium. J Mol Cell Cardiol. 2000; 32(12): 2361–2367.
  12. Mortensen SA, Rosenfeldt F, Kumar A, et al. The effect of coenzyme Q10 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.
  13. Poole-Wilson PA. Global differences in the outcome of heart failure: implications for clinical practice. J Am Coll Cardiol. 2008; 52(20): 1649–1651.
  14. Egwim C, Dixon B, Ambrosy AP, et al. Global variations in patient populations and outcomes in heart failure clinical trials. Curr Heart Fail Rep. 2017; 14(1): 30–39.
  15. Ferreira JP, Girerd N, Rossignol P, et al. Geographic differences in heart failure trials. Eur J Heart Fail. 2015; 17(9): 893–905.
  16. Kristensen SL, Martinez F, Jhund PS, et al. Geographic variations in the PARADIGM-HF heart failure trial. Eur Heart J. 2016; 37(41): 3167–3174.
  17. Littarru GP, Mosca F, Fattorini D, et al. Assay of coenzyme Q10 in plasma by a single dilution step. Methods Enzymol. 2004; 378: 170–176.
  18. Sokoll LJ, Baum H, Collinson PO, et al. Multicenter analytical performance evaluation of the Elecsys proBNP assay. Clin Chem Lab Med. 2004; 42(8): 965–972.
  19. O'Connor CM, Fiuzat M, Swedberg K, et al. Influence of global region on outcomes in heart failure β-blocker trials. J Am Coll Cardiol. 2011; 58(9): 915–922.
  20. Greene SJ, Fonarow GC, Solomon SD, et al. Global variation in clinical profile, management, and post-discharge outcomes among patients hospitalized for worsening chronic heart failure: findings from the ASTRONAUT trial. Eur J Heart Fail. 2015; 17(6): 591–600.
  21. Mentz RJ, Roessig L, Greenberg BH, et al. Heart failure clinical trials in east and southeast asia: understanding the importance and defining the next steps. JACC Heart Fail. 2016; 4(6): 419–427.
  22. Sharma KK, Gupta R, Agrawal A, et al. Low use of statins and other coronary secondary prevention therapies in primary and secondary care in India. Vasc Health Risk Manag. 2009; 5: 1007–1014.
  23. Ingwall JS. Energy metabolism in heart failure and remodelling. Cardiovascular Research. 2009; 81(3): 412–419.
  24. Mortensen SA. Perspectives on therapy of cardiovascular diseases with oenzyme Q10 (Ubiquinone). Clinical Investigator. 1993; 71(S8): S116–S123.
  25. Ferrari R, Guardigli G, Mele D, et al. Oxidative stress during myocardial ischaemia and heart failure. Curr Pharm Des. 2004; 10(14): 1699–1711.
  26. Opie LH. The metabolic vicious cycle in heart failure. Lancet. 2004; 364(9447): 1733–1734.
  27. Papucci L, Schiavone N, Witort E, et al. Coenzyme q10 prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scavenging property. J Biol Chem. 2003; 278(30): 28220–28228.
  28. Belardinelli R, Muçaj A, Lacalaprice F, et al. Coenzyme Q10 and exercise training in chronic heart failure. Eur Heart J. 2006; 27(22): 2675–2681.
  29. Littarru GP, Tiano L, Belardinelli R, et al. Coenzyme Q(10) , endothelial function, and cardiovascular disease. Biofactors. 2011; 37(5): 366–373.
  30. 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.
  31. Belardinelli R, Muçaj A, Lacalaprice F, et al. Coenzyme Q10 improves contractility of dysfunctional myocardium in chronic heart failure. Biofactors. 2005; 25(1-4): 137–145.
  32. Wilcox JE, Fonarow GC, Ardehali H, et al. "Targeting the Heart" in Heart Failure: Myocardial Recovery in Heart Failure With Reduced Ejection Fraction. JACC Heart Fail. 2015; 3(9): 661–669.