The Role of Mitochondria in Statin-Induced Myopathy

Bell, Gavin, Thoma, Anastasia, Hargreaves, Iain P ORCID: https://orcid.org/0000-0002-2760-5603 and Lightfoot, Adam P ORCID: https://orcid.org/0000-0003-1501-7879 (2024) The Role of Mitochondria in Statin-Induced Myopathy. Drug Safety. ISSN 0114-5916

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Abstract

Statins represent the primary therapy for combatting hypercholesterolemia and reducing mortality from cardiovascular events. Despite their pleiotropic effects in lowering cholesterol synthesis, circulating cholesterol, as well as reducing the risk of other systemic diseases, statins have adverse events in a small, but significant, population of treated patients. The most prominent of these adverse effects is statin-induced myopathy, which lacks precise definition but is characterised by elevations in the muscle enzyme creatine kinase alongside musculoskeletal complaints, including pain, weakness and fatigue. The exact aetiology of statin-induced myopathy remains to be elucidated, although impaired mitochondrial function is thought to be an important underlying cause. This may result from or be the consequence of several factors including statin-induced inhibition of coenzyme Q10 (CoQ10) biosynthesis, impaired Ca2+ signalling and modified reactive oxygen species (ROS) generation. The purpose of this review article is to provide an update on the information available linking statin therapy with mitochondrial dysfunction and to outline any mechanistic insights, which may be beneficial in the future treatment of myopathic adverse events.