MECHANISM OF ACTION 

  • Inhibition of HMG CoA reductase, preventing the hepatic conversion of mevalonic acid to cholesterol.
  • Reduced cholesterol synthesis in the liver results in decreased plasma LDL.

INDICATIONS

  • Prevention of cardiovascular events in patients with atherosclerotic disease or diabetes mellitus.
  • Primary hyperlipidaemia

CAUTIONS AND CONTRA-INDICATIONS

  • Active liver disease (caution needed in patients with alcohol dependence). Pregnancy and breastfeeding.

SIDE-EFFECTS

  • Rhabdomyolysis (rare but may manifest as myalgia, myositis or myopathy).
  • Altered liver function tests.
  • GI disturbance.

METABOLISM AND HALF-LIFE 

  • Metabolised by Cytochrome P450 (except pravastatin and rosuvastatin); clinical effects largely due to active metabolites.
  • t½ is variable – 2h for simvastatin; 14h for atorvastatin.

MONITORING 

  • Patients should be warned about possible rhabdomyolysis; if suspected check creatine kinase level.
  • LFTs should be checked 3 months following initiation.

DRUG INTERACTIONS

  • Increased risk of myopathy with fibrates, amiodarone and calcium channel blockers. Plasma concentration increased by grapefruit juice and macrolides.
  • Plasma concentration reduced by rifampicin.

IMPORTANT POINTS

  • Statins are more effective than any other lipid-lowering agents.
  • The greatest reduction of LDL is achieved with atorvastatin and rosuvastatin (60–65% reduction at maximum dose)