Risk assessment | Treatment guidelines | Options for statin intolerance

Risk assessment

  • CVD risk in FH patients is not adequately predicted by conventional risk assessment tools.
  • Risk factors are the same in FH as in the general population, however the cardiovascular risk factors are amplified in patients with FH therefore this patient group require detailed assessment and aggressive management.
  • Patients diagnosed with heterozygous FH should be managed according to the following algorithm recommended by the FH Australasia Network. FH patients are stratified into low, intermediate and high complexity cases.
  • This aims to make the most efficient use of limited primary and tertiary care resources and enables the rationalisation of management into:


    patients should be managed in primary care by their GP.

    • These patients have:
      • no CVD
      • no CVD risk factors and/or
      • attained their LDL cholesterol target on statin treatment.


    patients should receive shared care between the GP and the FH specialist centre.

    • These patients have:
      • stable CVD
      • stable CVD risk factors
      • nearly reached their LDL cholesterol target on statin treatment
      • minor statin intolerance
      • heterozygous FH and are under 18.


    patients should be managed by the FH specialist centre.

    • These patients have:
      • multiple uncontrolled risk factors
      • symptomatic CVD
      • recent myocardial infarction or revascularisation
      • not attained their LDL cholesterol target despite dual therapy
      • severe statin intolerance.

Treatment guidelines

  • Early treatment is highly beneficial. All FH patients require lifestyle management as well as lipid lowering therapy.
  • Long term drug therapy for FH patients can substantially reduce or remove the lifetime risk of CVD due to the genetic disorder and can lower event rates to be the same as those of the general population.
  • Statins are the cornerstone of cholesterol-modifying therapy and should be the initial treatment of all adult patients with FH.
  • LDL cholesterol should be reduced by >50% and/or a target of:
    • <2.5mmol/L should be achieved if there is no evidence of CVD
    • <1.8mmol/L if there is evidence of CVD.
  • FH patients may require combination drug therapy to achieve treatment targets. Ezetimibe and bile acid sequestrants are options for intensification of therapy.
  • Patients with FH should be counselled and prescribed lifestyle modifications such as
    • smoking cessation
    • reduced intake of saturated fats
    • physical activity and caloric intake to achieve and maintain a healthy body weight
    • limitation of alcohol consumption.
  • Dietary interventions and the use of nutraceuticals such as psyllium husk, plant sterols and red yeast rice extracts may be beneficial to enhance the lipid lowering being achieved with medication.

Options for statin intolerance

  • If the initial statin is not tolerated, consider discontinuing for 8 weeks then rechallenging with a lower dose or an alternate statin.
  • Avoid or decrease risk factors especially alcohol consumption.
  • Consider drug interactions with any other CYP3 mediated drugs. Liver enzymes (specifically, the cytochrome P-450 liver enzymes) are responsible for eliminating all statins from the body with the exception of Pravastatin and Rosuvastatin.
  • Therefore, drugs that block the action of these liver enzymes increase the levels of Simvastatin, Fluvastatin, and Atorvastatin (but not Pravastatin or Rosuvastatin) in the blood and can lead to the development of rhabdomyolysis.
  • Drugs or agents that block these enzymes include:
    • protease inhibitors
    • diltiazem
    • erythromycin, clarithromycin
    • cyclosporin
    • verapamil
    • St John’s Wort
    • grapefruit juice.
  • Intermittent dosing such as every other day, once or twice weekly.
  • Ezetimibe with or without low dose statin or intermittent dosing.
  • Co-enzyme Q at doses of 100 – 200mg daily.
  • Vitamin D supplementation in vitamin D deficiency.