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Statin myopathy

Authors
Robert S Rosenson, MD
Steven K Baker, MSc, MD
Section Editor
Mason W Freeman, MD
Deputy Editor
Gordon M Saperia, MD, FACC

INTRODUCTION

Statins are the primary class of medication used to lower serum cholesterol concentration for both primary and secondary prevention of coronary disease. (See "Treatment of lipids (including hypercholesterolemia) in primary prevention" and "Treatment of lipids (including hypercholesterolemia) in secondary prevention" and "Intensity of lipid lowering therapy in secondary prevention of cardiovascular disease".)

Statins are both effective and generally safe. Although muscle toxicity remains a concern, severe myopathy is unusual, affecting perhaps 0.1 percent of patients [1,2]. Muscle syndromes associated with statins, including myalgias and muscle injury, are discussed here. Other statin side effects are discussed separately. (See "Statins: Actions, side effects, and administration".)

PATHOGENESIS

The mechanism by which statins cause muscle toxicity is not well understood. They inhibit the conversion of HMG-CoA to mevalonic acid, which is an important early step in cholesterol synthesis.

Individual statins may have distinct effects on the synthesis of coenzyme Q10 (CoQ10, ubiquinone), which plays an important role in muscle cell energy production. It has been speculated that a reduction in ubiquinone in skeletal muscle may contribute to statin-induced muscle injury. Some studies have found that statins decrease skeletal muscle and plasma concentrations of ubiquinone [3-5]; however, other studies have not [6], and studies have come to different conclusions about whether statin treatment decreases levels of ubiquinone in skeletal muscle [5,7,8]. Long-term treatment with simvastatin (10 to 40 mg daily for >12 months) reduced ubiquinone content in skeletal muscles and decreased maximal mitochondrial oxidative phosphorylation capacity [9].

One study found increased levels of plant sterols in skeletal muscle in patients treated with high-dose statins [5]. Specifically, sitosterol was increased by approximately 50 percent. The authors of the study proposed that these increased cellular levels could contribute to the muscle toxicity of statins. Beta-sitosterol is an activator of AMP-activated protein kinase, which inhibits acetyl-CoA carboxylase. This results in reduced fat synthesis and increased beta-oxidation. Preliminary evidence suggests that statin-intolerant patients demonstrate increased fatty acid oxidation (FAO) in response to lovastatin, implicating an intrinsic FAO abnormality [10]. Statins increase the expression of mitochondrial carnitine acylcarnitine translocase and this effect may contribute to the alteration in FAO [11].

                              

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Literature review current through: Nov 2016. | This topic last updated: Fri Mar 11 00:00:00 GMT+00:00 2016.
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