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)