2.12 Lipid regulating drugs

Statins

MHRA Drug Safety Update (May 2014): Statins: benefits and risks

Classification of Statins

NICE CG181 groups statins according to their lipid lowering capability (see below). The guideline recommends the use of a high intensity statin (greater than 40% LDL-c lowering) of low acquisition cost in primary and secondary prevention of cardiovascular disease (CVD). If a person cannot tolerate a high intensity statin, prescribers should aim to treat with the maximum tolerated dose.

High intensity = Greater than 40%

  • Atorvastatin 20mg (43%), 40mg (49%), 80mg (55%)
  • Rosuvastatin 10mg (43%), 20mg (48%), 40mg (53%)
  • Simvastatin 80mg (42%) (non-formulary)

Medium intensity = 31-40%

  • Atorvastatin 10mg (37%)
  • Simvastatin 20mg (32%), 40mg (37%)
  • Rosuvastatin 5mg (38%)
  • Fluvastatin (non-formulary) 80mg (33%)

Low intensity = 20-30%

  • Simvastatin 10mg (27%)
  • Pravastatin (non-formulary) 10mg (20%), 20mg (24%), 40mg (29%)
  • Fluvastatin (non-formulary) 20mg (21%), 40mg (27%)
Atorvastatin
  • Tablets 10mg, 20mg, 40mg, 80mg (£1.40 = 20mg daily)

Indications and dose

  • Primary hypercholesterolaemia or combined (mixed) hyperlipidaemia (in patients who have not responded adequately to diet and other appropriate measures):
    • 10mg once daily, increased at intervals of at least 4 weeks to maximum 80mg once daily
  • Homozygous familial hypercholesterolaemia (in patients who have not responded adequately to diet and other appropriate measures):
    • 10mg daily, increased at intervals of at least 4 weeks to 40mg once daily or 80mg once daily
  • Heterozygous familial hypercholesterolaemia (in patients who have not responded adequately to diet and other appropriate measures):
    • 10mg daily, increased at intervals of at least 4 weeks to 40mg once daily or 80mg once daily
    • When combined with anion-exchange resin in heterozygous familial hypercholesterolaemia: 40mg once daily
  • Primary prevention of cardiovascular events in patients at high risk of a first cardiovascular event:
  • Secondary prevention of cardiovascular events (off-label use):

    Notes

    1. Atorvastatin chewable tablets are only for use where there is a clear indication of swallowing difficulty. They are significantly more expensive than standard formulations.
    2. The prescribing of atorvastatin for secondary prevention of cardiovascular disease is an off-label use.
    3. The BNF states that the starting dose of 20mg once daily is not licensed for the primary prevention of cardiovascular events.
    4. The maximum recommended dose for atorvastatin in conjunction with ciclosporin is 20mg daily.
    Rosuvastatin
    • Tablets 5mg, 10mg, 20mg, 40mg (£2.12 = 20mg daily)

    Indications

    • Prevention of cardiovascular events in patients at high risk of a first cardiovascular event
    • Secondary prevention of cardiovascular events (off-label use)

    Dose

    • 20mg once daily
    • Renal impairment:
      • eGFR 30–60 mL/minute/1.73 m2: Initially 5 mg once daily (do not exceed 20mg daily)
      • Contraindicated in patients with eGFR less than 30 mL/minute/1.73 m2
    • Adult patients of Asian origin: Initially 5mg once daily, then increased if necessary up to 20mg once daily, dose to be increased gradually at intervals of at least 4 weeks.
    • Adults aged 70 years and over: Initially 5mg once daily, then increased if necessary up to 40mg once daily, dose to be increased gradually at intervals of at least 4 weeks

    Notes

    1. Rosuvastatin is a high intensity statin at doses of 10mg and above. There is no evidence to suggest that cardiovascular events are less common when patients are treated with rosuvastatin compared to other statins and it has a considerably higher cost. It should be used solely in patients where all other appropriate statins have been considered and have either been demonstrated to be insufficiently effective, poorly tolerated or contraindicated.
    2. Rosuvastatin 5mg is a medium intensity statin. There is no evidence medium intensity rosuvastatin results in fewer cardiovascular events than other medium intensity statins and it has a considerably higher cost.
    3. The prescribing of rosuvastatin for secondary prevention of cardiovascular disease is an off-label use.
    4. The routine commissioning of rosuvastatin is accepted in Devon for the prevention of cardiovascular disease in patients who are intolerant of other appropriate statins (See Commissioning Policy for more information)
      Simvastatin
      • Tablets 10mg, 20mg, 40mg (£1.22 = 40mg daily)

      Indications and dose

      • Primary hypercholesterolaemia or combined (mixed) hyperlipidaemia (in patients who have not responded adequately to diet and other appropriate measures):
        • 10–20mg daily at night, adjusted at intervals of at least 4 weeks; maximum 80mg once daily at night (non-formulary, see note 1)
      • Homozygous familial hypercholesterolaemia (in patients who have not responded adequately to diet and other appropriate measures):
        • 40mg daily at night, adjusted at intervals of at least 4 weeks; maximum 80mg once daily at night (non-formulary, see note 1)
      • Prevention of cardiovascular events in patients with atherosclerotic cardiovascular disease or diabetes mellitus:
        • 40mg once daily at night as alternative to high intensity statin if not tolerated

        Notes

        1. Simvastatin 80mg is not routinely recommended, given the association of myopathy with simvastatin 80mg (See MHRA Drug Safety Update (May 2010): Simvastatin: increased risk of myopathy at high dose [80mg]) and the availability of alternative high intensity, lower acquisition cost statins. Prescribers should discuss the potential benefits and risks of changing to another statin with people currently treated with simvastatin 80mg.
        2. MHRA Drug Safety Update (August 2012) and MHRA Drug Safety Update (October 2012): The risk of simvastatin-induced myopathy and rhabdomyolysis is increased when it is taken with some other drugs:
          1. Simvastatin is contraindicated with ciclosporin, danazol and gemfibrozil.
          2. The maximum recommended dose for simvastatin in conjunction with amlodipine or diltiazem is 20mg daily.
        3. Moderate intensity simvastatin (20mg, 40mg) or low intensity (10mg) should be considered for primary prevention of CVD where intolerance to high intensity treatment, interactions, or contraindications occur.
        4. Discuss with people stable on moderate intensity statins (e.g. simvastatin 40mg) the potential risks and benefits of changing to a high intensity alternative statin at their next review.

        Bile acid sequestrants

        Colestyramine
        • Sachets 4g (sugar-free) (£60.95 = 16g daily)

        Indications

        • Hyperlipidaemias, particularly type IIa, in people who have not responded adequately to diet and other appropriate measures.
        • Primary prevention of coronary heart disease in men aged 35–59 years with primary hypercholesterolaemia who have not responded to diet and other appropriate measures

        Dose

        • 4g daily increasing by 4g at weekly intervals to 12–24g daily in 1–4 divided doses, then adjusted as required; maximum 36g daily

        Notes

        1. Do not offer bile acid sequestrants, for the prevention of CVD, to patients being treated for primary or secondary prevention, people with CKD, type 1 diabetes or type 2 diabetes.
        2. Colestyramine is indicated for reduction of plasma cholesterol in hypercholesterolaemia, such as in Fredrickson's Type II (high plasma cholesterol with normal or slightly elevated triglycerides).
        3. Colestyramine is a potent cholesterol lowering agent. It is recommended only for people who cannot tolerate other agents.

        Ezetimibe

        Ezetimibe
        • Tablets 10mg (£2.51 = 10mg daily)

        Indications and dose

        • Treatment of primary (heterozygous-familial and non-familial) hypercholesterolaemia:
          • 10mg once daily.

        Notes

        1. NICE TA385: Ezetimibe for the treatment of primary (heterozygous-familial and non-familial) Hypercholesterolaemia (February 2016)

        Fibrates

        The combination of a fibrate with a statin increases the risk of serious muscle toxicity, especially rhabdomyolysis, and should be used with caution.

        MHRA Drug Safety Update (December 2010): Fibrates: first-line treatment not recommended.

        Do not routinely offer fibrates for the prevention of CVD to people being treated for primary or secondary prevention, people with CKD or type 1 diabetes or type 2 diabetes (NICE CG181)

        Bezafibrate
        • Tablets 200mg (£7.25)
        • Modified Release tablets 400mg (£7.12)

        Indications and dose

        • Adjunct to diet and other appropriate measures in mixed hyperlipidaemia if statin contra-indicated or not tolerated, or in severe hypertriglyceridaemia:
          • Standard release: 200mg three times daily
          • Modified release: 400mg once daily
          Fenofibrate
          • Capsules 67mg (£21.68)
          • Capsules 200mg - 267mg (£4.37 = 267mg daily)
          • Tablets 160mg (£4.36)

          Indications

          • Adjunct to diet and other appropriate measures in mixed hyperlipidaemia if statin contra-indicated or not tolerated, or in severe hypertriglyceridaemia
          • Adjunct to statin in mixed hyperlipidaemia if triglycerides and HDL-cholesterol inadequately controlled in patients at high cardiovascular risk

          Dose

          • 67mg: initially 3 capsules daily, increased if necessary to 4 capsules daily (max 3 daily if used with statin)
          • 200mg, 267mg: one capsule daily
          • 160mg: one tablet daily

          Notes

          1. Fenofibrate has similar efficacy to bezafibrate in the reduction of triglycerides and is more potent than in terms of LDL reduction and HDL elevation.

          Nicotinic acid group

          Nicotinic acid
          • Niaspan® modified release tablets 500mg, 1g (unlicensed preparation)

          Indications

          • Nicotinic acid is included in the formulary only for treatment of patients with resistant dyslipidaemia and should only be initiated by a Consultant Endocrinologist or Cardiologist.

          Omega-3 fatty acid compounds

          Omacor®

          (Omega-3-acid ethyl esters)

          • Capsules 1g (£28.48 = 2 capsules daily)

          Indications

          • Adjunct to diet and statin in IIb or III hypertriglyceridaemia; adjunct to diet in type IV hypertriglyceridaemia

          Notes

          1. Do not offer omega-3 fatty acids for the prevention of CVD to patients being treated for primary or secondary prevention, people with CKD, type 1 diabetes or type 2 diabetes (NICE CG181)
          2. A European Medicines Agency (EMA) review confirms omega-3 fatty acid medicines are not effective in preventing further heart problems after a heart attack, for more information see here
          3. Omacor is recommended only for people with severe hypertriglyceridaemia (>10mmol/L) who are cannot tolerate a fibrate.
          4. Each capsule contains eicosapentaenoic acid (EPA) 460mg and decosahexaenoic acid (DHA) 380mg
          5. Omacor increases bleeding time; patients receiving anticoagulant therapy must be monitored and the dosage of anticoagulant adjusted if necessary

          Lipid modifying drugs

          Alirocumab
          • Solution for injection, pre-filled pen 75mg/1ml, 150mg/1ml

          Notes

          1. NICE TA393: Alirocumab (Praluent) is recommended as an option for treating primary hypercholesterolaemia or mixed dyslipidaemia, only when the criteria of the NICE TA is met (June 2016).
          Evolocumab
          • Solution for injection, pre-filled pen 140mg/1ml
          • Solution for injection, pre-filled syringe 140mg/1ml

          Notes

          1. NICE TA394: Evolocumab (Repatha) is recommended as an option for treating primary hypercholesterolaemia or mixed dyslipidaemia, only when the criteria of the NICE TA is met (June 2016).
          Volanesorsen
          • Solution for injection, pre-filled syringes 285mg in 1.5ml

          Notes

          1. NICE HST13: Volanesorsen (Waylivra) is recommended, within its marketing authorisation, as an option for treating familial chylomicronaemia syndrome in adults with genetically confirmed familial chylomicronaemia syndrome who are at high risk of pancreatitis, and when response to diet and triglyceride-lowering therapy has been inadequate (October 2020)
          Last updated: 01-02-2021

           

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