Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations

Abstract

Introduction Musculoskeletal manifestations are well-recognized side effects of treatment with statins. New advances in this field have appeared in recent years. This review focuses on the diagnosis of these conditions and their underlying pathogenesis, in particular immune-mediated necrotizing myopathy. Areas covered Clinical phenotypes including rhabdomyolysis, myalgia and/or mild hyperCKemia, self-limited toxin statin myopathy, and immune-mediated necrotizing myopathy are herein described. Therapeutic recommendations and a diagnostic algorithm in statin-associated myopathy are also proposed. The etiology and pathogenesis of statin-induced myopathy has mainly focused on the anti-HMGCR antibodies and the responsibility of the immune-mediated necrotizing myopathy is discussed. The fact that patients who have not been exposed to statins may develop statin-associated autoimmune myopathy with anti-HMGCR antibodies is also addressed. The literature search strategy included terms identified by searches of PubMed between 1969 and December 2017. The search terms ‘myositis’, ‘statin-induced autoimmune myopathy’, ‘immunemediate necrotizing myopathy’, ‘statins’, ‘muscular manifestations’, and ‘anti-HMGCR antibodies’ were used. Expert commentary Full characterization of the known phenotypes of statin toxicity and the specific role of the anti-HMGCR in those exposed and not exposed (i.e. juvenile forms) to statins and in some types of neoplasms is of paramount relevance.

Polypharmacy induced myositis

“…Statins inhibit hydroxymethylglutaryl coenzyme reductase, which is important for mevalonate production, a precursor to cholesterol synthesis . Mevalonate is used to anchor guanosine triphosphatases, and if disrupted can affect cytoskeleton formation resulting in rhabdomyolysis.…”

Polymyositis, Dermatomyositis, and Statins: A Review

“…These fully human monoclonal antibodies (e.g. evolucumab, alirocumab), which act against the proprotein convertase subtilisin/kexyn type 9, could be an alternative to statin therapy in severe cases of drug toxicity, such as rhabdomyolysis [1]. Clinical studies comparing statins versus statins + anti-PCSK9 found no differences in muscle and CPK side effects between the two groups [69,70].…”

“…Due to the wide diffusion of statins, which have the undoubted merit of increasing the survival rate in patients affected by cardiovascular disease, particular attention should be paid to their side effects. The most common ones are toxic myopathies, affecting 2-20% of patients [1], that generally resolve after drug discontinuation. The risk of statin myopathy and creatine phosphokinase (CPK) increase is dose-dependent.…”

Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges

“…Statins are essential drugs in the treatment of dyslipidaemia, and thus in the prevention of cardiovascular diseases. Despite statins are generally safe, a variety of myopathies have been reported following treatment (Selva-O'Callaghan et al, 2018). In fact, 10.5% of patients on statin therapy may experience myalgia, which is the most common side effect (Bruckert, Hayem, Dejager, Yau, & Bégaud, 2005).…”