Statin Induced Muscle Toxicity - Summary



Clinical Presentation:

 • Elevations of serum creatine kinase with proximal myalgia and weakness without skin involvement



Epidemiology

 • 10% to 15% of individuals on statin therapy experience Statin-Associated Muscle Symptoms (SAMS)

 • 1 of 100,000 patients taking a statin, IMNM



Duration:

 • The onset of muscle symptoms: weeks to months after the initiation of statin therapy / may occur at any time during treatment



Statin-Induced Myalgia/Myopathy Symptoms:

 • Proximal symmetric muscle weakness

 • Soreness

 • Myalgia

 • Myositis

 • Rhabdomyolysis

 • Difficulty raising the arms above the head, arising from a seated position, or climbing stairs

 • Fatigue or tiredness

 • Myoglobinuria



DDX:

 • Inflammatory myopathy, rhabdomyolysis, toxic myopathy, hypothyroid-induced myopathy, Guillain-Barré syndrome (GBS), systemic lupus erythematosus (SLE), polymyositis, dermatomyositis, inclusion body myositis antisynthetase syndrome, immune-mediated necrotizing myopathy (IMNM), Lambert-Eaton myasthenic syndrome (LEMS), systemic sclerosis.



Statins → Inflammatory myopathies such as

 • Statin-induced myopathy (SAMS) → Direct muscle injury

 • Immune-mediated necrotizing myopathy (IMNM) → Antibodies to hydroxymethylglutaryl (HMG)-CoA reductase (HMGCR)

	- Necrotizing myopathy: Inflammatory statin myopathy is characterized by a macrophagocytic infiltrate engulfing necrotic muscle fibers



Risk of myopathy appears to be lowest with:

 • Fluvastatin

 • Pravastatin

 • Pitavastatin

Risk of muscle injury - Statins extensively metabolized by CYP3A4:

 • Lovastatin

 • Simvastatin

 • Atorvastatin



Diagnosis:

 • CK:

	- SAMS <20,000 IU/I

	- IMNM: 1,000–20,000 IU/I

 • SAMS clinical index (SAMS-CI)

 • EMG shows small-amplitude motor-unit potentials with increased spontaneous activity

 • If statin-associated muscle symptoms (SAMS) fail to resolve after DC statin — then need to consider: immune-mediated necrotizing myopathy (IMNM)

 • Muscle biopsy if symptoms do not resolve after DC Statin



Treatment:

 • Stop statin

 • Oral steroid, methotrexate, intravenous immunoglobulin (IVIG), and/or rituximab



#SAMS #Statin #muscle #toxicity #myopathy #diagnosis #management #treatment