2.12 Lipid-regulating drugs

Drugs used for lipid modification not listed below:

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, or special liquid preparations, 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 maximum recommended dose for atorvastatin in conjunction with ciclosporin is 20mg daily.
  4. The BNF states that the starting dose of 20mg once daily is not licensed for the primary prevention of cardiovascular events.
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.

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 = three daily)
  • Capsules 200mg, 267mg (£4.37 = 267mg daily)
  • Tablets 160mg (£4.36 = one daily)

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.

Omega-3 fatty acid compounds

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)

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.

Omacor® (Omega-3-acid ethyl esters) is recommended for patients with severe hypertriglyceridaemia levels (greater than 10mmol/L) who cannot tolerate a fibrate.

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 is recommended as an option for treating primary hypercholesterolaemia and mixed dyslipidaemia only when the criteria of the NICE TA are met (June 2016) (CCG commissioned)
Evolocumab
  • Solution for injection, pre-filled pen 140mg/1ml
  • Solution for injection, pre-filled syringe 140mg/1ml

Notes

  1. NICE TA394: Evolocumab is recommended as an option for treating primary hypercholesterolaemia and mixed dyslipidaemia only when the criteria of the NICE TA are met (June 2016) (CCG commissioned)
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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