This application is in response to RFA-OD-09-003 and addresses broad Challenge Area (05): Comparative Effectiveness Research and specific Challenge Topic AT 102: Complementary and Alternative Medicine. Statins markedly reduce the incidence of cardiac events. These drugs are generally well-tolerated but can produce a dose-related myopathy with symptoms ranging from """"""""mild"""""""" myalgia, muscle cramps and weakness to life-threatening rhabdomyolysis. Rhabdomyolysis is rare, but mild myopathic symptoms occur in approximately 10% of patients treated with high-dose statins. The cause of statin myopathy is not known, but statins inhibit cholesterol synthesis early in the mevalonate pathway thereby reducing other end products including ubiquinone or Coenzyme Q10 (CoQ10). A variety of evidence supports CoQ10 as a possible etiologic agent: statins reduce serum CoQ10 levels;several studies have reported reduced muscle CoQ10 levels in myopathic patients;some investigators have reported evidence of mitochondrial dysfunction during statin treatment;and CoQ10 has been used successfully to treat inherited mitochondrial disorders. Anecdotal reports from physicians and patients also suggest that CoQ10 supplementation is effective, but such reports cannot exclude a placebo effect. Despite this suggestive evidence, only two small studies have examined CoQ10 in statin myalgic patients and these have yielded contrasting results. Consequently, we will recruit 135 patients with prior statin-associated muscle complaints. Subjects will be treated with simvastatin 20 mg daily or placebo in a double-blind, cross-over design to determine if their myalgic symptoms reoccur. Subjects with recurrent symptoms during simvastatin treatment, but not during placebo, will be withdrawn from statin therapy for one month, restarted on simvastatin and randomly assigned to placebo or CoQ10. Subjects will be called weekly to inquire about muscle complaints. The intensity of skeletal muscle pain at 8 weeks will be the primary endpoint. We will also record time to onset of recurrent muscle symptoms as well as serum CoQ10 levels, skeletal muscle strength and endurance and maximal aerobic exercise capacity to examine some more objective measures of muscle performance and exercise capacity. In 2008, $400 million was spent on CoQ10 for a variety of therapies, including the treatment of statin myopathy. We have studied statin myopathy since 1990 and consider CoQ10 an intriguing treatment approach, but its effectiveness must be determined to justify patients'expenditures, especially in these difficult economic times. Statins markedly reduce the incidence of cardiac events. These drugs are generally well-tolerated but can produce muscle side effects such as muscle cramps and weakness, which can ultimately require withdrawal of medications for statin-intolerant subjects. The current study investigates the utility of Coenzyme Q10 supplementation in patients with statin-associated muscle side effects to determine if Coenzyme Q10 supplementation is a novel therapeutic approach to improving statin tolerance.
Statins markedly reduce the incidence of cardiac events. These drugs are generally well-tolerated but can produce muscle side effects such as muscle cramps and weakness, which can ultimately require withdrawal of medications for statin-intolerant subjects. The current study investigates the utility of Coenzyme Q10 supplementation in patients with statin-associated muscle side effects to determine if Coenzyme Q10 supplementation is a novel therapeutic approach to improving statin tolerance.
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