statin myopathy

Etiology

• most common adverse effect of statins
  • dose-dependent, statin specific dependency
  • hydrophilic statins (fluvastatin, pravastatin, & rosuvastatin) less likely than lipophilic statins (atorvastatin, simvastatin, lovastatin)
• a statin-associated autoimmune-necrotizing myopathy with autoantibody directed against HMG-CoA reductase, the pharmacologic target of statins
  • occurs in a minority of patients with statin-induced myopathy
  • continues to progress even after discontinuing statin
  • diet may be a trigger in the absence of statin prescription
• risk factors
  • older age
  • female gender
  • renal insufficiency
  • coadministration of fibrates, niacin, & CYP3A4 inhibitors (macrolides, cyclosporine, itraconazole)
  • hypothyroidism
  • alcoholism
• genetic predisposition

Epidemiology

• adverse effects occur in 17% of patients, mostly myopathy
• myopathy in 31% of persons initiating statin, resulting in discontinuation of statin in 13%
• 2-3 cases of statin-associated autoimmune-necrotizing myopathy per 100,000
  • may be more common 3/1000 in some Native American populations

Pathology

• statin use attenuates substrate use during maximal exercise, induces muscle fatigue during repeated muscle contractions, & decreases muscle mitochondrial oxidative capacity
• evidence presented that statin-associated autoimmune-necrotizing myopathy may be associated with a specific HLA subtype

Genetics

• genetic variants in SLCO1B1 gene may predispose to statin myopathy
• LILRB5 variant rs12975366: T > C Asp247Gly may predispose to statin myopathy

Clinical manifestations

• myalgias, muscle tenderness, muscle cramping, proximal muscle weakness
• hyporeflexia may be noted
• low back pain has been reported
• no rach

Laboratory

• increase in serum creatine kinase (mild to rhabdomyolysis)
  • may occur with normal serum creatine kinase
• serum C-reactive protein generally normal
• SLCO1B1 genotyping (simvastatin)
• LILRB5 genotyping (no corresponding Loinc)

Diagnostic procedures

• normal electromyography, generally not indicated

Complications

• acute renal failure to due rhabdomyolysis
  • increased risk of hospitalization for acute renal failure with high-dose or potent statin

Differential diagnosis

• muscle tenderness distinguishes from inflammatory myopathy
  • polymyositis, dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy
    • inclusion body myositis with slow onset typically preexisting weakness for 5 years at presentation
    • polymyositis:
      • muscle pain & tenderness, if present, are mild
      • serum creatine kinase elevated
• diabetic amyotrophy with no involvement of upper extremities
• myasthenia gravis presents with fluctuating weakness of extraocular, bulbar, & proximal limb muscles & is painless.

Management

• stop statin if
  • serum creatine kinase > 10-fold upper reference value, or severe myalgias
  • elevated serum creatine kinase (mild-moderate), known CVD, on atorvastatin, stop atorvastatin & start rosuvastatin 20-40 mg when myalgias have resolved
• adverse effects occur in 13% of patients after rechallange with a different statin
• symptoms usually subside within a month or two after stopping the statin, but they sometimes persist longer
• fluvastatin, pravastatin, & rosuvastatin associated with less risk of myopathy than other statins
  • simvastatin & pravastatin score best in overall safety profile
• CoQ10 may or may not help myalgias
  • CoQ10 of no benefit
• no benefit of vitamin D
• immunosuppression may be required in patients with autoimmune- necrotizing statin myopathy

More general terms

• toxic myopathy; drug-induced myopathy

More specific terms

• immune-mediated necrotizing myopathy (IMNM)

Additional terms

• HMG CoA reductase inhibitor (statin)