Statins Neuromuscular Adverse Effects

Abstract

Statins are drugs widely prescribed in high-risk patients for cerebrovascular or cardiovascular diseases and are, usually, safe and well tolerated. However, these drugs sometimes may cause neuromuscular side effects that represent about two-third of all adverse events. Muscle-related adverse events include cramps, myalgia, weakness, immune-mediated necrotizing myopathy and, more rarely, rhabdomyolysis. Moreover, they may lead to peripheral neuropathy and induce or unmask a preexisting neuromuscular junction dysfunction. A clinical follow up of patients assuming statins could reveal early side effects that may cause neuromuscular damage and suggest how to better modulate their use. In fact, statin dechallenge or cessation, or the alternative use of other lipid-lowering agents, can avoid adverse events. This review summarizes the current knowledge on statin-associated neuromuscular adverse effects, diagnosis, and management. It is conceivable that the incidence of neuromuscular complications will increase because, nowadays, use of statins is even more diffused than in the past. On this purpose, it is expected that pharmacogenomic and environmental studies will help to timely predict neuromuscular complications due to statin exposure, leading to a more personalized therapeutic approach.

Keywords: muscle adverse effects; myasthenia; neuromuscular complications; peripheral neuropathy; statins and myopathy.

Figure 1

Muscle biopsy: hematoxylin and eosin staining demonstrating the loss of normal muscle architecture, and extensive myofiber necrosis (right arrow). (from Madgula, A. S. et al., 2020 Cureus) [66].

Figure 2

Muscle histology (magnification ×200, scale bar 50 μm). (a) Gomori trichrome stain showing increased fiber diameter variability, pale degenerating fibers (arrows). (b) Acid phosphatase stain showing phagocytes invading degenerating fibers (asterisks) and endomysial inflammatory cells (arrowheads). (c) ATPase pH 4.6 stain showing the normal checkerboard pattern of type 1 (dark) and type 2 (2a pale; 2b brownish) fibers. (d) MHC-1 immunofluorescence showing cytoplasmic and sarcolemmal positivity in some necrotic fibers (asterisks) and membrane staining of inflammatory cells (arrow) (from Barp A. et al., 2021 Neurol Sci) [67].

Figure 3

Strategy for statin-associated muscle symptoms.