Coenzyme Q10 for statin-related myopathy (short)

Banach M, et al. Effects of coenzyme Q10 on statin-induced myopathy: A meta-analysis of randomized controlled trials. Mayo Clinic Proc 2015;90:24-34.

Bottom line: Coenzyme Q10 has no effect on statin-related myopathy. Clinicians should investigate and manage other causes and risk factors for myalgias. In those with likely statin-related myalgias, strategies include alternate-day statin dosing, decreasing the dose, or switching to a different statin.

 

Context

• ~5-10% of patients report myalgias while taking statins
  • Described as a heaviness/stiffness/cramping or weakness/loss of strength, more often in the lower limbs, that's worse with exertion, with a median onset 4 weeks after starting the statin
  • Risk factors for statin-related myalgia:
    • Higher statin dose
    • Demographics: Older age, female sex, asian
    • Other conditions: CKD, electrolyte disorders, hypothyroidism, existing myalgias
• One of the hypothesized mechanisms of statin-related myopathy is the interference of Coenzyme Q10 (CoQ10) production

Methods

• Systematic review of MEDLINE, Embase, the Cochrane Library, and Scopus up to May 2014
  • No attempts to uncover unpublished or gray literature
• Included 6 RCTs of CoQ10 versus placebo in 302 patients with statin-induced myopathy that reported on outcomes of changes in creatine kinase (CK) or myalgia
• Evaluated study quality using the flawed Jadad score
  • Although reviewers rated all trials as "high quality", trials often had questionable allocation concealment and blinding, biasing results in favor of the CoQ10 group
• Meta-analyzed using a random-effects model to account for heterogeneity in study design

Interventions

• I: CoQ10 100-400 mg/day x30 days (1 trial) to 12 weeks (5 trials)
• C: Placebo (in at least 1 trial, "placebo" not inert (vitamin E) and looked different from CoQ10 capsule)

Results

• No statistically significant difference in muscle pain in 5 trials with high heterogeneity (I^2 = 89%)
  • 2/5 trials reported statistically significant differences (at least 1 of which wasn't truly placebo-controlled or properly blinded), whereas 3/5 reported no difference or trend towards increased myalgia
  • Standard mean difference -0.53 (95% confidence interval -1.33 to 0.28,)
    • No single validated statin myalgia scale, so various scales used in different studies
• No statistically or clinically significant difference in CK in 5 trials
  • Mean difference +11.69 units (95% confidence interval -14.25 to +37.63, p=0.38)
• Sensitivity analysis suggested no greater chance of benefit with higher doses
• Did not report other important outcomes, such as % of patients able to tolerate statins, or able to increase dose

Additional evidence

• An RCT of 38 patients with confirmed statin-induced myalgia found no reduction in myalgia or CK, or improvement in muscle strength and endurance with CoQ10 600 mg/d versus placebo.
  • Of note, the investigators of this trial went to great lengths to confirm that myalgia was related to statins with a double-blind cross-over trial of simvastatin and placebo. Only ~33% of 120 patients initially enrolled for history of muscle complaints while on a statin had confirmed statin-related myalgia (& not with the placebo) during the cross-over phase. This is a good reminder that many cases "statin intolerance due to muscle pain" that we see in practice are in fact unrelated to statins. If they have an appropriate indication for a statin, these patients should be re-challenged on a statin, with consideration of an alternate statin at a lower dose that can later be titrated as tolerated.