see also:

• hyperlipidaemia

• HMGCoA reductase inhibitors, 'statins', are the first line drugs to use for most patients with hyperlipidaemia or mod-high risk of atherosclerotic cardiovascular disease.
• they are extremely efficacious and more than 90% of patients can tolerate them with negligible or no adverse effects.
• statins differ in efficacy, with the earlier statins lowering LDL to a similar extent to bile resins such as cholestyramine and nicotinic acid. The newer statins, atorvastatin and rosuvastatin, are considerably more efficacious in lowering LDL cholesterol, but there is little evidence as yet that this further improves long-term clinical outcomes.
• most of the effect of the statins occurs at less than the maximum dose. If the patient's target cholesterol is not reached, adding another drug may therefore have more effect than increasing the statin dose.
• a large UK study reported in 2017 suggests the lipophilic statins (eg. simvastatin and atorvastatin) decrease 4yr mortality by ~40% in patients with breast cancer but this was not seen with the hydrophilic statins (eg. fluvastatin)
• statins also inhibit macrophage activity and possibly could reduce gingivitis which is thought to have a causal association with atherosclerosis

• if adverse effects occur, more than 90% appear within the first three months.
• adverse effects tend to be dose related and are similar between statins.
• if a patient has adverse effects from one statin, the dose can be lowered, given in divided doses or every second day. Alternatively, the patient can be switched to another statin or a controlled-release formulation.
• myopathy / myositis / muscle aches and pains
  • if CK > 300IU/ml then consider with-holding for 1wk and rpt testing
• a rise in the liver transaminases can occur
  • liver function tests are recommended before and during treatment.
  • measure liver function every six months and if the transaminases are greater than twice the upper limit, stop the statin and repeat the liver function test in 3–4 weeks.
  • true hepatitis is rare

• as per Aust. Prescriber Feb 2014

• clear high risk of cardiovascular disease (CVD) such as:
  • established CVD
  • diabetic aged > 60yrs
  • diabetic with microalbuminaemia
  • moderate or severe chronic renal disease with persistent proteinuria or eGFR < 45 mL/min/1.73m2
  • familial hypercholesterolaemia
  • systolic BP >= 180mmHg
  • diastolic BP >= 110mmHg
  • serum total cholesterol > 7.5 mmol/L (assuming LDL > 6.5 mmol/L or non-HDL > 5.5 mmol/L)
• for other patients
  • those at high 5-year CVD risk (>= 15% risk) according to the Framington Risk Equation see http://www.cvdcheck.org.au
  • those at moderate 5-year CVD risk according to Framington Risk Equation but who either:
    • are in a specific population for which the Risk Equation underestimates their risk such as:
      • ethnicity (eg. Aboriginal and Torres Strait Islanders)
      • diabetics aged 45-60yrs
      • obesity
      • low socioeconomic status
    • after 3-6 months of lifestyle risk modification does not reduce their absolute risk
    • BP is persistently > 160/100 mmHg
    • FH of premature CVD

• any Aboriginal and Torres Strait Islander
• any indication as per age < 75 yrs BUT clinical judgment of risk-benefits taking into account:
  • likely benefits and risks of Rx
  • life expectancy
  • comorbidities and quality of life
  • the patient's personal values
  • if using http://www.cvdcheck.org.au, use age 74 years to avoid artificially inflating calculated absolute risk

• 1st HMG CoA reductase inhibitor, mevastatin (Compactin), was discovered in 1976 when it was isolated from cultures of the fungus Penicillium citrinum
• all have similar effects in inhibiting HMG Co-A reductase, the main differences between them being the nature of the enzymes by which they are metabolized, giving different potential drug–drug interactions and whether they are lipophilic or hydrophilic which may have significant differences in mortality benefits
• lovastatin 1976 discovered in Aspergilus terreus - CYP metabolism: 3A and 2C8
• simvastatin 1986 - lipophilic; CYP metabolism: 3A4
• pravastatin 1986 - CYP metabolism:
• atorvastatin 1990 - lipophilic; CYP metabolism: 3A4
• fluvastatin 1990 - hydrophilic; CYP metabolism: mostly 2C9 (also 3A4 and 2C8)
• cerivastatin 1996 - CYP metabolism: 2C8 and 3A4 ⇒ significant interactions hence withdrawn from market
• pitavastatin 1997 - CYP metabolism: 2C9
• rosuvastatin 2001 - CYP metabolism: 2C9