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Lipid modification - primary and secondary CVD prevention - Management
How should raised creatine kinase be managed in people taking a statin?

  • If creatine kinase (CK) is five or more times the upper limit of normal:
    • Stop statin treatment immediately.
    • Check renal function.
    • Monitor creatine kinase fortnightly.
    • Consider secondary causes of myopathy if the CK level remains elevated:
      • Underlying muscle disorders, renal impairment, hypothyroidism, or alcohol abuse.
      • Concomitant use of other lipid-modifying drugs (e.g. fibrates and nicotinic acid).
      • Concomitant use of cytochrome P450 inhibitors (e.g. ciclosporin, macrolide antibiotics [e.g. erythromycin and clarithromycin], azole antifungal [e.g. itraconazole and ketoconazole], grapefruit juice).
    • If symptoms resolve and CK levels return to normal, then re-introduction of the statin or introduction of an alternative statin may be considered at the lowest dose, and with close monitoring.
  • If the CK level is less than five times the upper limit of normal:
    • If there are no muscle symptoms:
      • Continue the statin.
      • Advise the individual to report immediately any unexplained muscular symptoms.
      • Consider further checks of CK to ensure that values are not increasing.
    • If there are muscle symptoms:
      • Continue the statin.
      • Monitor symptoms.
      • Check CK concentrations regularly (for example, fortnightly) if CK values continue to increase.
      • Stop the statin, or seek specialist advice if muscle symptoms are severe or CK values continue to increase.
Clarification / Additional information
  • Statins and other lipid-modifying drugs can rarely cause myopathy and rhabdomyolysis. The exact mechanism is uncertain, but risk factors include [CSM, 2004]:
    • Underlying muscle disorders.
    • Renal impairment.
    • Untreated hypothyroidism: this is known to increase the risk of statin-induced myopathy [Bar et al, 2007] and is a recognized cause of dyslipidaemia [BTA et al, 2006].
    • Alcohol abuse.
    • Older age (older than 70 years of age).
    • Concomitant use of other lipid-modifying drugs (i.e. fibrates, nicotinic acid).
    • A history of myopathy with any lipid-modification therapy.
    • Drug interactions (e.g. with drugs inhibiting cytochrome P450 enzymes).
Basis for recommendation

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