2.12 Lipid regulating drugs

Statins

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

Medium intensity = 31-40%

  • Atorvastatin 10mg (37%)
  • Simvastatin 20mg (32%), 40mg (37%)
  • Rosuvastatin (non-formulary) 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%)

*Based on: Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003; 326: 1423.

Atorvastatin
  • Tablets 20mg, 40mg, 80mg (£1.04 = 20mg daily)

Indications

  • Primary hypercholesterolaemia, heterozygous familial hypercholesterolaemia, homozygous familial hypercholesterolaemia or combined (mixed) hyperlipidaemia in patients who have not responded adequately to diet and other appropriate measures.
  • Prevention of cardiovascular events in patients at high risk of a first cardiovascular event.

Dose

  • Primary prevention of cardiovascular events: 20mg once daily See Management of blood lipids for more details.
  • Secondary prevention of cardiovascular events: 80mg once daily (max. 20mg daily in CKD) See Management of blood lipids for more details
  • Primary hypercholesterolaemia and combined hyperlipidaemia: 10mg once daily, increased at intervals of at least 4 weeks to maximum 80mg once daily
  • Familial hypercholesterolaemia: 10mg daily, increased at intervals of at least 4 weeks to 40mg once daily or 80mg once daily
  • Combined with anion-exchange resin in heterozygous familial hypercholesterolaemia: 40mg once daily.

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.
Simvastatin
  • Tablets 10mg, 20mg, 40mg (£0.84 = 40mg daily)

Indications

  • Primary hypercholesterolaemia
  • Homozygous familial hypercholesterolaemia or combined (mixed) hyperlipidaemia where diet and other appropriate measures have proved inadequate.
  • Prevention of cardiovascular events in patients with atherosclerotic cardiovascular disease or diabetes mellitus

Dose

  • Prevention of cardiovascular events: 40mg once daily at night as alternative to high intensity statin if not tolerated.
  • Primary hypercholesterolaemia, combined hyperlipidaemia: 10–20mg daily at night, adjusted at intervals of at least 4 weeks; maximum 80mg once daily at night
  • Homozygous familial hypercholesterolaemia: 40mg daily at night, adjusted at intervals of at least 4 weeks; maximum 80mg once daily at night

Notes

  1. Simvastatin 80mg is not routinely recommended, given the association of myopathy with simvastatin 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. The risk of simvastatin-induced myopathy and rhabdomyolysis is increased when it is taken with some other drugs. MHRA issued guidance (August 2012):
    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 potency statin at their next review.
Rosuvastatin

In line with in NICE CG 181, rosuvastatin is not recommended for the prevention of cardiovascular disease. Equivalent lipid-lowering capability statins are available for all strengths of rosuvastatin. There are no outcome data for rosuvastatin in patients with hypercholesterolaemia. The acquisition costs of rosuvastatin are significantly greater than any other statin. It should be noted however, that specialists may recommend its use for individual patients where proven intolerance to other statins, unacceptable side effects (where dose reduction does not alleviate symptoms), co-morbidities or interactions preclude the use of any other statin.

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 (£26.31 = 10mg daily)

Indications

  • Ezetimibe is indicated for the treatment of primary (heterozygous-familial and non-familial) hypercholesterolaemia

Dose

  • 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.

Bezafibrate
  • Tablets 200mg (£3.53)
  • Modified Release tablets 400mg (£7.12)

Indications

  • Adjunct to diet and other appropriate measures in mixed hyperlipidaemia if statin contra-indicated or not tolerated, or in severe hypertriglyceridaemia

Dose

  • Standard release: 200mg, 3 times daily
  • Modified release: 400mg once daily
Fenofibrate
  • Capsules 67mg (£21.10)
  • Capsules 200mg - 267mg (£5.08 = 267mg daily)
  • Tablets 160mg (£6.69)

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. Do not offer fibrates, for the prevention of CVD, to patients being treated for primary or secondary prevention or people with CKD, type 1 diabetes or type 2 diabetes (NICE CG 181)
  2. 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 recommended for treating primary hypercholesterolaemia and mixed dyslipidaemia (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 for treating primary hypercholesterolaemia and mixed dyslipidaemia (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)

 

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