Important new medicine information

PCSK9 inhibitors (sometimes also shown as PCSK9i) are a new type of medicine for lowering cholesterol in the blood.

PCSK9 is a protein that’s made in the liver. Research has shown that people with high levels of PCSK9 tend to have high cholesterol throughout their lives and develop heart disease early. But people with low levels tend to have low cholesterol and a lower risk of heart disease. This discovery has led to the development of medicines called PCSK9 inhibitors to lower cholesterol.

There are two PCSK9 inhibitors, Repatha (Evolocumab) and Praluent (Alirocumab), and others are being developed at the moment.

In clinical studies, these medicines have lowered people’s cholesterol levels by more than half. Early research shows they could prevent strokes and heart attacks too.

These have AMBER status

Bempedoic acid is an adenosine triphosphate citrate lyase (ACL) inhibitor which inhibits cholesterol synthesis in the liver, thereby lowering LDL-cholesterol.

Used for primary hypercholesterolaemia or mixed dyslipidaemia in patients who have not responded adequately to other appropriate measures [in combination with a statin, or with a statin and other lipid-lowering therapies, or with other lipid-lowering therapies or alone if a statin contra-indicated or not tolerated] 

NICE TA694 Bempedoic acid with ezetimibe for treating primary hypercholesterolaemia or mixed dyslipidaemia (April 2021)

NHS Somerset has commissioned bempedoic acid with ezetimibe and has AMBER status

Inclisiran (Leqvio) is NHS Somerset commissioned GREEN status. For treating primary hypercholesterolaemia or mixed dyslipidaemia. as per NICE TA733 – requested to support statin potency optimisation and addition of ezetimibe before Inclisiran initiation (agreed SPF Nov-21).

NICE TA733 Inclisiran for treating primary hypercholesterolaemia or mixed dyslipidaemia

Icosapent ethyl is NHS Somerset commissioned GREEN status with statin therapy for reducing the risk of cardiovascular events in people with raised triglycerides.

NICE TA805 Icosapent ethyl with statin therapy for reducing the risk of cardiovascular events in people with raised triglycerides

Therapeutic AreaFormulary ChoicesCost for 28
(unless otherwise stated)
Rationale for decision / comments
2.12 Lipid-regulating drugsRelated guidance:
Improving outcomes for patients with cardiovascular disease (CVD) is a clinical priority in the NHS Long-Term Plan. To support delivery of this part of the NHS Long-Term Plan, the Accelerated Access Collaborative (AAC) Lipid Management Rapid Uptake Product (RUP) Working Group have developed a NICE-endorsed clinical pathway along with a companion document for statin intolerance:
Summary of national guidance for lipid management for primary and secondary prevention of cardiovascular disease (CVD); and
Statin intolerance pathway.

Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease
Peripheral arterial disease: diagnosis and management
[TA694] Bempedoic acid with ezetimibe for treating primary hypercholesterolaemia or mixed dyslipidaemia
Refer to the above summary to identify patients for whom a statin may be beneficial. NICE recommends using a high intensity statin i.e that which can reduce LDL by 40% from baseline. This comprises atorvastatin above 20mg and rosuvastatin above 10mg daily. First line is atorvastatin 20mg for primary prevention and atorvastatin 80mg for secondary prevention where contra- indications and tolerances allow.
Monitoring of statin treatment for primary and secondary prevention:
• People on a statin should be advised to seek medical advice if they develop muscle symptoms (pain, tenderness or weakness). If this occurs, creatine kinase should be measured.
•Creatine kinase should not be routinely monitored in asymptomatic people who are being treated with a statin.
• Baseline liver enzymes should be measured before starting a statin. Liver function (transaminases) should be measured within 3 months of starting treatment and at 12 months, but not again unless clinically indicated.
• People who have liver enzymes (transaminases) that are raised but are less than 3 times the upper limit of normal should not be routinely excluded from statin therapy.
• If a person develops an unexplained peripheral neuropathy, statins should be discontinued and specialist advice sought.

It is recommended that attempts should always be made to get patients to national cholesterol levels with statin monotherapy, using all formulary statins, before consideration is given to adding in or changing to another agent.

A summary of drug–statins interactions is included in this chapter.
Statins
First line:Atorvastatin


10mg tablets: £0.83
20mg tablets: £0.97
40mg tablets: £1.23
80mg tablets: £1.88
Atorvastatin is first line statin for all new patients unless contra-indicated. It is included in the formulary for:
• Hypercholesterolaemia
• Primary prevention of cardiovascular events (where 10 year CVD risk ≥ 10%-give 20mg
• Secondary prevention of CV events (give 80mg if tolerated or not contra-indicated)
First line:Rosuvastatin5mg tablets: £1.56
10mg tablets: £1.51
20mg tablets: £2.07
40mg tablets: £2.70

5mg capsules: £8.52
10mg capsules: £9.54
20mg capsules: £12.72
40mg capsules: £15.12
Rosuvastatin is contra-indicated in patients with severe renal impairment (creatinine clearance <30 ml/min. The 40mg dose is contra-indicated in moderate renal impairment (creatinine clearance < 60 ml/min).

Pravastatin and Rosuvastatin have a different metabolic pathway so may be tolerated when Simvastatin or Atorvastatin are not.
Second line:Simvastatin




as Simvador®

10mg tablets: £0.76
20mg tablets: £0.90
40mg tablets: £1.04
80mg tablets: £1.62

10mg tablets: £0.60
20mg tablets: £0.69
40mg tablets: £0.77
80mg tablets: £1.82
Please note:
• Simvastatin should be prescribed at night to optimise effect.
• Simvastatin 10mg should only be prescribed for patients who cannot tolerate a higher evidence-based dose of statin therapy
Simvastatin doses should not exceed 20mg for patients on Amiodarone, Verapamil, Amlodipine or Diltiazem
• See BNF or SPC for further information on interactions
• There is an increased risk of myopathy associated with high-dose (80mg) simvastatin. The 80mg dose should be considered only in patients with severe hypercholesterolaemia and high risk of cardiovascular complications who have not achieved their treatment goals on lower doses, when the benefits are expected to outweigh the potential risks. (see MHRA Drug Safety Update May 2010; 3 (10))
Second line:Pravastatin10mg tablets: £0.91
20mg tablets: £1.10
40mg tablets: £1.36
It should be noted that the maximum reduction in total cholesterol which can be expected from Pravastatin is 24%. However, pravastatin is not liver metabolised like the others, which may explain why it is generally better tolerated.
Other lipid lowering drugsIn general, the evidence for an effect on outcomes is less robust than for statin therapy. Additional monitoring may be required, particularly when Fibrates or Nicotinic Acid are used in combination with statins, due to increased risk of myopathy.
Ezetimibe10mg tablets: £2.08[TA385] Ezetimibe for treating primary heterozygous-familial and non-familial hypercholesterolaemia
This guidance should be used with NICE's guidelines on cardiovascular disease: risk assessment and reduction, including lipid modification and familial hypercholesterolaemia: identification and management.

Ezetimibe monotherapy is recommended as an option for treating primary (heterozygous‑familial or non‑familial) hypercholesterolaemia in adults in whom initial statin therapy is contraindicated.

Ezetimibe monotherapy is recommended as an option for treating primary (heterozygous‑familial or non‑familial) hypercholesterolaemia in adults who cannot tolerate statin therapy, defined as the presence of clinically significant adverse effects that represent an unacceptable risk to the patient or that may reduce compliance with therapy.

Ezetimibe, co‑administered with initial statin therapy, is recommended as an option for treating primary (heterozygous‑familial or non‑familial) hypercholesterolaemia in adults who have started statin therapy when:

1. serum total or low‑density lipoprotein (LDL) cholesterol concentration is not appropriately controlled (defined as based on individual risk assessment according to national guidance on managing CV disease in the relevant populations) either after appropriate dose titration of initial statin therapy or because dose titration is limited by intolerance to the initial statin therapy and

2. a change from initial statin therapy to an alternative statin is being considered.

When prescribing ezetimibe co‑administered with a statin, ezetimibe should be prescribed on the basis of lowest acquisition cost.

Healthcare professionals should offer adults with FH a referral to a specialist with expertise in FH if treatment with the maximum tolerated dose of a high-intensity statin and ezetimibe does not achieve a recommended reduction in LDL-C concentration of greater than 50% from baseline (that is, LDL-C concentration before treatment).
Local specialist advice is to also consider checking triglyceride levels & consider fibrate.

See NICE CG71 Nov 2017 for further information
FibratesFenofibrate micronized
160mg tablets: £3.56Consider use only in severe hypertriglyceridaemia. Do not routinely offer fibrates for the prevention of CVD to any of the following:
• people who are being treated for primary prevention
• people who are being treated for secondary prevention
• people with CKD
• people with type 1 diabetes
• people with type 2 diabetes.
Nicotinic acidSpecialist recommendation ONLYThese lipid lowering drugs are usually initiated in secondary care by clinical biochemists for patients with complex dyslipidaemias.
Nicotinic acid and bile acid sequestrants : do not use as for fibrates above
Bile acid sequestrants (Anionic exchange resins)Colestyramine (Questran®)
Colesevelam Colestipol
Tredaptive (Nicotinic acid + laropiprant) withdrawn from market Jan 2013. HPS2-THRIVE trial failed to show reduced risk of CV events & incidence of serious adverse events in the treatment group was higher.
Omega-3-acid ethyl esters (Omacor®) now non-formulary. NICE MI:secondary prevention (CG172) Nov 2013 says not to offer people omega 3 fatty acid capsules or supplemented foods to prevent another MI. Similarly NICE CG181 Lipid modification Sept 2016 does not recommend using omega-3 fatty acids to help prevent CVD

Summary of National Guidance for Lipid Management for Primary and Secondary Prevention of CVD

https://www.england.nhs.uk/aac/publication/summary-of-national-guidance-for-lipid-management/

Statin interactions