Statin therapy and plasma coenzyme Q10 concentrations—A systematic review and meta-analysis of placebo-controlled trials

Authors:

Maciej Banach | Corina Serban | Sorin Ursoniu | Jacek Rysz | Paul Muntner | Peter P. Toth | Steven R. Jones | Manfredi Rizzo | Stephen P. Glasser | Gerald F. Watts | Roger S. Blumenthal | Gregory Y.H. Lip | Dimitri P. Mikhailidis | Amirhossein Sahebkar | Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group
First published: 17 July 2015 | https://doi.org/10.1016/j.phrs.2015.07.008

Abstract:

Abstract
Statin therapy may lower plasma coenzyme Q10 (CoQ10) concentrations, but the evidence as to the significance of this effect is unclear. We assessed the impact of statin therapy on plasma CoQ10 concentrations through the meta-analysis of available RCTs. The literature search included selected databases up to April 30, 2015. The meta-analysis was performed using either a fixed-effects or random-effect model according to I2 statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The data from 8 placebo-controlled treatment arms suggested a significant reduction in plasma CoQ10 concentrations following treatment with statins (WMD: −0.44 μmol/L, 95%CI: −0.52, −0.37, p < 0.001). The pooled effect size was robust and remained significant in the leave-one-out sensitivity analysis. Subgroup analysis suggested that the impact of statins on plasma CoQ10 concentrations is significant for all 4 types of statins studied i.e. atorvastatin (WMD: −0.41 μmol/L, 95%CI: −0.53, −0.29, p < 0.001), simvastatin (WMD: −0.47 μmol/L, 95% CI: −0.61, −0.33, p < 0.001), rosuvastatin (WMD: −0.49 μmol/L, 95%CI: −0.67, −0.31, p < 0.001) and pravastatin (WMD: −0.43 μmol/L, 95%CI: −0.69, −0.16, p = 0.001). Likewise, there was no differential effect of lipophilic (WMD: −0.43 μmol/L, 95%CI: −0.53, −0.34, p < 0.001) and hydrophilic statins (WMD: −0.47 μmol/L, 95%CI: −0.62, −0.32, p < 0.001). With respect to treatment duration, a significant effect was observed in both subsets of trials lasting <12 weeks (WMD: −0.51 μmol/L, 95%CI: −0.64, −0.39, p < 0.001) and ≥12 weeks (WMD: −0.40 μmol/L, 95%CI: −0.50, −0.30, p < 0.001). The meta-analysis showed a significant reduction in plasma CoQ10 concentrations following treatment with statins. Further well-designed trials are required to confirm our findings and elucidate their clinical relevance.

  1. S. Pepe et al.
    Coenzyme Q 10 in cardiovascular disease
    Mitochondrion
    (2007)
  2. E. Fontaine et al.
    A ubiquinone-binding site regulates the mitochondrial permeability transition pore
    J. Biol. Chem.
    (1998)
  3. D.A. Groneberg et al.
    10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells
    Int. J. Biochem. Cell Biol.
    (2005)
  4. A. Mellors et al.
    The inhibition of mitochondrial peroxidation by ubiquinone and ubiquinol
    J. Biol. Chem.
    (1966)
  5. P. Sirvent et al.
    New insights into mechanisms of statin-associated myotoxicity
    Curr. Opin. Pharmacol.
    (2008)
  6. G.M. Camerino et al.
    Statin or fibrate chronic treatment modifies the proteomic profile of rat skeletal muscle
    Biochem. Pharmacol.
    (2011)
  7. M. Banach et al.
    Effects of coenzyme Q10 on statin-induced myopathy
    Mayo Clin. Proc.
    (2015)
  8. L. Marcoff et al.
    The role of coenzyme Q10 in statin-associated myopathy: a systematic review
    J. Am. Coll. Cardiol.
    (2007)
  9. I. Buhaescu et al.
    Mevalonate pathway: a review of clinical and therapeutical implications
    Clin. Biochem.
    (2007)
  10. G. Dallner et al.
    Regulation of ubiquinone metabolism
    Free Radic. Biol. Med.
    (2000)
  11. E. Ashton et al.
    Why did high-dose rosuvastatin not improve cardiac remodeling in chronic heart failure? Mechanistic insights from the UNIVERSE study
    Int. J. Cardiol.
    (2011)
  12. W.A. Oranje et al.
    Effect of atorvastatin on LDL oxidation and antioxidants in normocholesterolemic type 2 diabetic patients
    Clin. Chim. Acta
    (2001)
  13. C.H. Strey et al.
    Endothelium-ameliorating effects of statin therapy and coenzyme Q10 reductions in chronic heart failure
    Atherosclerosis
    (2005)
  14. M. Banach et al.
    Lipids, blood pressure and kidney update 2014
    Pharmacol. Res.
    (2015)
  15. M. Banach et al.
    Lipid, blood pressure meta-analysis collaboration G. In reply–coenzyme Q10 and statin-induced myopathy
    Mayo Clin. Proc.
    (2015)
  16. G.P. Littarru et al.
    10 and statins: biochemical and clinical implications
    Mitochondrion
    (2007)
  17. S. Larsen et al.
    Simvastatin effects on skeletal muscle: relation to decreased mitochondrial function and glucose intolerance
    J. Am. Coll. Cardiol.
    (2013)
  18. L. Bazzichi et al.
    ATP, calcium and magnesium levels in platelets of patients with primary fibromyalgia
    Clin. Biochem.
    (2008)
  19. Y.S. Chatzizisis et al.
    Coenzyme Q10 depletion: etiopathogenic or predisposing factor in statin associated myopathy
    Am. J. Cardiol.
    (2008)
  20. C. Vaklavas et al.
    Molecular basis of statin-associated myopathy
    Atherosclerosis
    (2009)
  21. M.A. Desbats et al.
    Genetic bases and clinical manifestations of coenzyme Q10 (CoQ 10) deficiency
    J. Inherit. Metab. Dis.
    (2015)
  22. A. Ayer et al.
    CoQ 10 in heart failure and ischemic heart disease
    Annu. Rev. Nutr.
    (2015)
  23. A. Bargossi et al.
    Exogenous CoQ10 preserves plasma ubiquinone levels in patients treated with 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors
    Int. J. Clin. Lab. Res.
    (1994)
  24. K. Kędziora-Kornatowska et al.
    Effects of coenzyme Q10 supplementation on activities of selected antioxidative enzymes and lipid peroxidation in hypertensive patients treated with indapamide. A pilot study
    Arch. Med. Sci.
    (2010)
  25. M. Banach et al.
    Statin intolerance—an attempt at a unified definition. Position paper from an International Lipid Expert Panel
    Arch. Med. Sci.
    (2015)