Background Coenzyme Q10 (CoQ10) supplementation is the most popular therapy for statin myalgia among both physicians and patients despite limited and conflicting evidence of its efficacy. Objective This study examined the effect of coenzyme Q10 (CoQ10) supplementation on simvastatin-associated muscle pain, muscle strength and aerobic performance in patients with confirmed statin myalgia. Methods Statin myalgia was confirmed in 120 patients with prior symptoms of statin myalgia using an 8-week randomized, double-blind crossover trial of simvastatin 20 mg/d and placebo. Forty-one subjects developed muscle pain with simvastatin but not with placebo and were randomized to simvastatin 20 mg/d combined with CoQ10 (600 mg/d ubiquinol) or placebo for 8 weeks. Muscle pain (Brief Pain Inventory [BPI]), time to pain onset, arm and leg muscle strength, and maximal oxygen uptake (VO2max) were measured before and after each treatment. Results Serum CoQ10 increased from 1.3±0.4 to 5.2±2.3 mcg/mL with simvastatin and CoQ10, but did not increase with simvastatin and placebo (1.3±0.3 to 0.8±0.2) (p<0.05). BPI pain severity and interference scores increased with simvastatin therapy (both p<0.01), irrespective of CoQ10 assignment (p=0.53 and 0.56). There were no changes in muscle strength or VO2max with simvastatin with or without CoQ10 (all p>0.10). Marginally more subjects reported pain with CoQ10 (14 of 20 vs 7 of 18; p=0.05). There was no difference in time to pain onset in the CoQ10 (3.0±2.0 weeks) vs. placebo (2.4±2.1 wks) groups (p=0.55). A similar lack of CoQ10 effect was observed in 24 subjects who were then crossed over to the alternative treatment. Conclusions Only 36% of patients complaining of statin myalgia develop symptoms during a randomized, double-blind crossover of statin vs placebo. CoQ10 supplementation does not reduce muscle pain in patients with statin myalgia. Trial Registration NCT01140308; www.clinicaltrials.gov

Background Statins are the most commonly prescribed and effective medications for reducing low-density lipoprotein levels. Some patients experience myopathic symptoms during statin treatment. The etiology is not known, but depletion of mevalonate pathway metabolites, including coenzyme Q10 (CoQ10), has been suggested. CoQ10 supplementation has been recommended to patients who experience myalgic symptoms despite a lack of conclusive evidence supporting its utility. Objective The Co-Enzyme Q10 in Statin Myopathy study is designed to examine the effect of CoQ10 supplementation on the extent and intensity of muscle pain during treatment with simvastatin. Methods We will recruit patients with a documented history of myalgia during statin treatment. The presence of statin-related myalgia will be confirmed in a crossover run-in trial during which presence and absence of symptoms will be documented during statin and placebo treatment, respectively. Individuals with myalgic symptoms while on statin but not placebo will be randomized to receive simvastatin 20 mg daily plus either 600 mg daily of CoQ10 or placebo. Muscle pain intensity will be documented during weekly phone calls using the Brief Pain Inventory (Short Form) (BPI-SF). Treatment will continue for 8 weeks or until muscle symptoms are reported continuously for one week or become intolerable, and then subjects will crossover to the alternative treatment (CoQ10 or placebo). Results This study is an ongoing clinical trial. Conclusions This study will determine the utility of CoQ10 for reducing pain intensity in myalgic patients and will provide guidance for clinicians treating patients with hypercholesterolemia who are intolerant to statins.

Statins reduce arterial stiffness but are also associated with mild muscle complaints. It is unclear whether individuals with muscle symptoms experience the same vascular benefit or whether statins affect striated and smooth muscle cells differently. We examined the effect of simvastatin treatment on arterial stiffness in patients who did versus those who did not exhibit muscle symptoms. Patients with a history of statin-related muscle complaints (n = 115) completed an 8 wk randomized, double-blind, cross-over trial of daily simvastatin 20 mg and placebo. Serum lipids and pulse wave velocity (PWV) were assessed before and after each treatment. Muscle symptoms with daily simvastatin treatment were reported by 38 patients (33%). Compared to baseline, central PWV decreased (P = 0.01) following simvastatin treatment but not placebo (drug ∗ time interaction: P = 0.047). Changes in central PWV with simvastatin treatment were not influenced by myalgia status or time on simvastatin (P ≥ 0.15). Change in central PWV after simvastatin treatment was inversely correlated with age (r = −0.207, P = 0.030), suggesting that advancing age is associated with enhanced statin-mediated arterial destiffening. In patients with a history of statin-related muscle complaints, the development of myalgia with short-term simvastatin treatment did not attenuate the improvement in arterial stiffness.

Background and aims Low vitamin D (VITD) may contribute to statin-associated muscle symptoms (SAMS). We examined the influence of baseline and change in VITD in patients with verified SAMS. Methods SAMS was verified in 120 patients with prior statin muscle complaints using 8-week randomized, double-blind crossover trials of simvastatin (SIMVA) 20 mg/d and placebo. 25 (OH)vitamin D was measured at each phase of the trial. Results Forty-three patients (35.8%) experienced muscle pain on SIMVA but not placebo, exhibiting confirmed SAMS. VITD (mean ± standard deviation) prior to SIMVA treatment were not different between patients who did (31.7 ± 12.1 ng/mL, n=43) or did not (31.6 ± 10.3 ng/mL, n=77) develop SAMS and did not predict SAMS (p=0.96). The change in VITD with SIMVA treatment was not different between patients with and without SAMS (0.3 ± 5.9 vs. 0.2±8.3 ng/mL, respectively) and did not predict SAMS (p=0.96). The proportion of patients classified as VITD deficient (<20 ng/mL) did not differ between patients with (n=16) and without (n=10) SAMS (χ2=1.45; p=0.23), nor did the proportion of patients classified as VITD insufficient (<30 ng/mL) (n=42 vs. 48; χ2<0.01 and p=0.94). Both baseline and on-statin VITD were inversely related to the change in creatine kinase (CK) with statin therapy (p=0.01 and 0.02, respectively), independent of SAMS (p=0.36 and 0.35). Conclusions Baseline VITD, VITD deficiency/insufficiency and changes in VITD with statin therapy do not predict SAMS in patients with rigorously verified SAMS. However, low VITD may exacerbate statin-induced muscle injury and could contribute to SAMS development with a longer duration of statin treatment.

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