Lipid Management

This guideline is intended for primary care clinicians working within NHS South West London (SWL) to support the assessment, initiation and optimisation of lipid lowering therapy in adults for the primary and secondary prevention of cardiovascular disease (CVD).

CVD remains a leading cause of morbidity and mortality. Effective lipid management significantly reduces the risk of major cardiovascular events. This guideline provides a practical, stepwise approach to lipid optimisation in line with NICE guidance, NICE CKS and local medicines optimisation pathways, supporting consistent, evidence-based care across NHS SWL.

Importance of Lipid Management

  • People with high cholesterol who also have other risk factors (e.g. high blood pressure, diabetes, smoking) are at significantly greater risk of CVD and have most to gainfrom a reduction in cholesterol.​ Every 1mmol/l reduction in low-density lipoproteins cholesterol (LDL-C) reduces risk of a cardiovascular event by 25%.
  • Lifestyle change is important to reduce cardiovascular risk. Where this is ineffective or in people at highest risk (e.g. pre-existing CVD or familial hypercholesterolaemia (FH), drug therapy with statins and other medications is very effective.​
  • FH is high-risk but very treatable. Half of men with FH will have a heart attack or stroke before age 50 and a third of women before age 60. Statins are highly effective at reducing this risk.
  • One in six patients with CVD are not receiving lipid lowering therapy, large numbers of people are not taking the recommended dose or intensity statins. Optimising treatment in these patients will prevent any more heart attacks and strokes.
  • The importance of improving lipid management to reduce cardiovascular events is shown in the UCL Partners ‘size of the prize’.

Lipid modification

NICE guidance and NICE CKS on CVD prevention and lipid modification include key information on the following:

  • lifestyle measures to prevent CVD.
  • initial lipid measurement and monitoring.
  • advice on shared decision making.
  • lipid-lowering treatment for both primary and secondary prevention.
  • optimising statins and alternative options.
  • assessing treatment response.

Pharmacological Management

Primary Prevention

  • Refer to NICE CKS – Primary prevention of CVD.
  • Refer to SWL Netformulary for RAG ratings.
  • Be aware that in certain groups, CVD risk may be underestimated. Refer to CKS information above for detail of patients who may be offered statin treatment for the primary prevention of CVD without the need for a formal risk assessment.
  • First line therapy:
    • High intensity statin (HIS) (e.g. atorvastatin 20 mg daily or rosuvastatin 10mg daily) can be initiated in primary care.
  • Treatment target:
    • Aim for greater than 40% reduction in non-high density lipoprotein cholesterol (non-HDL-C) from baseline.
  • Review lipid profile after 3 months
    • Assess adherence and tolerability.
    • Titrate statin dose up to maximum tolerated dose e.g. atorvastatin 80mg daily if target not achieved. Note: refer to Summary of Product Characteristics for any dose adjustment required e.g. drug interactions
    • Add ezetimibe 10 mg daily if required which can be initiated in primary care.
  • Different statin intensities and corresponding LDL-C improvement are included in the BNF and NICE CKS.

Refer to Patients with High Cardiovascular Risk – Primary Prevention and Lipid Management Options and LDL-C Reduction table for visual summaries.

Secondary Prevention

  •  Refer to NICE CKS – Secondary prevention of CVD.
  • Initial Management:
    • Offer high dose, high intensity statin e.g. atorvastatin 80 mg daily or rosuvastatin 20mg daily.
  • Treatment Targets:
    • LDL-C less than 2.0 mmol/L or non-HDL-C less than 2.6 mmol/L.
  • Review lipid profile after 2 to 3 months, if target not met:
    • Address any adherence issues and reinforce lifestyle measures.
    • Consider adding ezetimibe (can be initiated in primary care) to maximum tolerated statin.
    • Consider for referral for:
      • Monotherapy Bempedoic acid (Amber 2 – initiation by specialist and stabilisation for 3 months before transfer to primary care). Note: across SWL bempedoic acid can be used as an alternative in statin-intolerant patients with ezetimibe (Amber 1- can be initiated in primary care on recommendation of a specialist) or without ezetimibe as monotherapy (Amber 2- specialist initiation and stabilisation for 3 months before continuing in primary care).
    • At any point consider referral for icosapent ethyl (Amber 2 – specialist initiation and stabilisation for 3 months before continuing in primary care) in addition to statins and/or other lipid lowering therapies if fasting triglycerides (TGs) greater than or equal to 1.7 mmol/L (or non-fasting TGs greater than 2.1mmol/L) and LDL-C greater than 1.04 mmol/L and less than or equal to 2.6mmol/L.
  • Prescribing information for each lipid-lowering therapy is provided in NICE CKS.

Refer to visual summary of patients with Established Cardiovascular Disease – Secondary Prevention.

Statin Intolerance

  • Statin intolerance is defined as the presence of clinically significant adverse effects that represent an unacceptable risk to the patient or that may reduce adherence to therapy. This typically means trying two different statins at different doses.
  • The national statin intolerance pathway and NICE CKS – Statins can be used when presented with a patient showing clinically significant adverse effects that limit adherence or pose unacceptable risk to the patient.

Discuss with the patient if signs and symptoms are statin intolerance or due to a statin reluctance/non-adherence. Consider that a statin at any dose reduces CV risk – if a patient cannot tolerate a high intensity statin, aim to treat with a maximum tolerated dose of a statin, but if symptoms persist consider alternative options/lipid clinic referral.  

  • Refer to Recommended Criteria for Referral to Lipid Clinic if intolerance persists (SWL Hospitals).
  • Further information:
    • For Statin Related Muscle (SRM) symptoms Pathway such as symmetrical pain/weakness in large proximal muscle groups, worsened by exercise- measure creatine kinase (CK). If CK normalises and symptoms have resolved for at least 2 weeks, rechallenge and offer a low or moderate dose of HIS e.g. atorvastatin 10 to 20mg daily or rosuvastatin 5 to10mg daily.
    • Non-standard dosing may be recommended by specialist clinics e.g. rosuvastatin 5mg weekly or three times a week (off label use but accepted practice).​
    • If tolerating ezetimibe but not achieving lipid lowering targets: consider inclisiran (Red – hospital or specialist only prescribing) via lipid clinics if for secondary prevention or consider initiating bempedoic acid. Note: across SWL bempedoic acid can be used as an alternative in statin-intolerant patients with ezetimibe (Amber 1- can be initiated in primary care on recommendation of a specialist) or without ezetimibe as monotherapy (Amber 2- specialist initiation and stabilisation for 3 months before continuing in primary care).

Familial Hypercholesterolaemia (FH) pathway

FH review in primary care: Identification of FH by age and lipid profile

  • Review medical records and invite appropriate patients for a face-to-face screening appointment. Refer to NICE Guideline FH: identification and management, NICE CKS – hypercholesterolaemia for case finding and diagnosis of patients as well as drug management and visual summary of FH pathway.
  • Refer to visual summary- FH Review in Primary Care: Supporting Identification, diagnosis, Management and Coding.
  • Consider lifestyle and medication interventions and schedule follow up. Signpost to patient information for FH and lifestyle interventions.
  • Ensure coding is correct for each patient adjust as required- suggested SNOMED Coding:
    • Single gene FH: Familial hypercholesterolemia (disorder) SCTID: 398036000 Family history of familial hypercholesterolemia (situation) SCTID: 443454007.
    • Other high cholesterol coding: Hypercholesterolemia (disorder) SCTID: 13644009 Family history: Hypercholesterolemia (situation) SCTID: 160314003.
  • Eligibility criteria for a FH (R134) genomic test state that patients need to have a Dutch or Welsh lipid clinic score of 6 or more or meet the Simon Broome criteria, which are;
    • Definite FH: defined as total cholesterol greater than 6.7mmol/L or LDL-C greater than 4.0mmol/L in a child aged younger than 16 years or total cholesterol greater than 7.5mmol/L or LDL-C greater than 4.9mmol/L in an adult (levels either pre-treatment or highest on treatment).
      • Plus: Tendon xanthomas in patient or in 1st degree relative (parent, sibling, child) or in 2nd degree relative (grandparent, uncle, aunt).
      • Or: DNA-based evidence of an LDL receptor mutation or familial defective apo B 100 or a PCSK9 mutation.
    • Possible FH: defined as total cholesterol greater than 6.7mmol/L or LDL-C greater than 4.0mmol/L in a child aged younger than 16 years or total cholesterol greater than 7.5mmol/L or LDL-C greater than 4.9mmol/L in an adult (levels either pre-treatment or highest on treatment) and at least one of the following:
      • Family history of myocardial infarction: younger than 50 years of age in a 2nd degree relative or younger than 60 in a 1st degree relative or
      • Family history of raised cholesterol greater than 7.5mmol/L in adult 1st or 2nd degree relative or greater than 6.7mmol/L in child or sibling aged younger than 16 years.

Hypertriglyceridaemia

  • In all cases address possible secondary causes and appropriate lifestyle interventionsbefore referral to lipid clinic.
    • Secondary causes include excessive alcohol intake (e.g. greater than 40 units/week), poorly controlled/new diabetes (e.g. HbA1c greater than 53 mmol/mol, TG – raising medication (e.g. steroids), hypothyroidism (e.g. TSH greater than 15), Metabolic Dysfunction-Associated Steatotic Liver Disease, acute/chronic liver disease, renal disease (e.g. CKD 3), obesity, smoking.
  • Fibrate therapy:
    • Such as fenofibrate 160mg daily (can be initiated in primary care). If fibrate is contra-indicated or not tolerated seek specialist advice, although this therapy is not associated with cardiovascular outcome benefits.
    • Discontinue: if creatinine increases to less than 50% (adjust dose as per SPC) and if ALT/AST is greater than three times the Upper Limit Normal (ULN).
    • Check creatine kinase (CK) if muscular symptoms: The combination of fibrate with statin increases risk of myopathy.
  • Icosapent ethyl therapy▼ (Amber 2 – specialist initiation and stabilisation for 3 months before continuing in primary care):
    • Recommended by NICE for patients with CVD (secondary prevention) in combination with statin therapy where fasting TG is greater than or equal to 1.7mmol/L and LDL-C greater than 1.04 mmol/L and less than or equal to 2.6mmol/L.
    • Adherence: this medication must be taken as prescribed to be effective and so adherence and tolerability should be monitored at each review.
    • If patients cannot take 2 (998 mg capsules) capsules twice a day, then stop therapy.
    • Pulse checks are also recommended at each review to identify potential AF, refer for ECG if indicated and manage associated stroke risk if AF is diagnosed.
  • Omega-3-Acid Ethyl Esters– Amber 2 in selected patients, omega 3 fatty acids may be initiated by lipid specialists for control of triglycerides for prevention and treatment of acute pancreatitis only (not for CVD- see MHRA 2024).
    • Specialist to initiate and prescribe one month treatment before transfer of prescribing to primary care. For short-term use.
    • In line with NHSE guidance, omega-3 fatty acids are non-formulary for all other indications and should not be initiated in primary or secondary care.
  • Refer to visual summary for the management of hypertriglyceridaemia.

Lipid therapy in individuals with HIV

  • NICE CKS – Primary Prevention notes that the British HIV Association (BHIVA) recommends all people living with HIV aged 40 years or older should be offered statin treatment for primary prevention of CVD irrespective of lipid profile or estimated CVD risk, and that this should be initiated and monitored in primary care.
  • Some anti-retrovirals (ARV), such as boosted protease inhibitors (e.g. darunavir, ritonavir, cobicistat or atazanavir) and efavirenz can increase lipids, while others are more lipid-friendly. Consider referring patients with persistently elevated lipids to their HIV clinic for optimisation of their antiretroviral regimen.
  • NICE CKS – prescribing information includes interactions between statins and ARV. For further information and advice about interactions with ARV refer to HIV drug interactions checker, REPRIEVE Trial, or seek Advice & Guidance from HIV specialist team (see below). Refer to visual summary for common statin/ARV interactions and recommended doses.
  • HIV specialist contact details below:
    • St Helier Hospital Rosehill Clinic: 0208 296 4773.
    • Kingston Hospital Wolverton Centre: 0208 934 2844.
    • Croydon Hospital Heath Clinic: 0208 401 3007.

Referral to secondary care in SWL

  • The aim of hospital clinics is to focus on patients with primary hyperlipidaemia and on specialist medications.
  • Before referral to lipid clinic: Identify and address potential secondary causes of hyperlipidaemia, such as uncontrolled diabetes mellitus, obesity, excess alcohol consumption, untreated hypothyroidism, proteinuria and some medications, for example, thiazide diuretics, ciclosporin, steroids and antipsychotics.
  • For hypercholesterolaemia exclude hypothyroidism (check TSH), chronic renal disease or nephrotic syndrome, variant diets (zero carbohydrate, protein supplements).
  • For hypertriglyceridaemia exclude new/uncontrolled diabetes (check HbA1c), excess alcohol intake and fatty liver (may require referral to gastro if FIB-4 score indicates).
  • For suspected familial hypercholesterolaemia exclude secondary causes and refer to the hospital lipid clinic for genetic testing.
  • Refer to visual summary of Recommended Criteria For Referral to Lipid Clinic (SWL Hospitals).
  • SWL Lipid clinic contact details:
    • St George’s Hospital Vascular risk lipid clinics- via NHS e-referral (ERS) or via cardiology lipid management advice and guidance.
    • Croydon University Hospital- Advice and guidance via ERS.

Resources/supporting materials

References/resources

  1. NICE TA393; Alirocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia. 
  2. NICE TA394; Evolocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia.
  3. NICE TA385; Ezetimibe for treating primary heterozygous-familial and non-familial hypercholesterolaemia.
  4. NICE TA694; Bempedoic acid with ezetimibe for treating primary hypercholesterolaemia or mixed dyslipidaemia.
  5. NICE TA733: Inclisiran for treating primary hypercholesterolaemia or mixed dyslipidaemia.
  6. Lewington S, et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007;370:1829–1839
  7. Silverman MG, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA. 2016;316(12):1289–1297
  8. BHIVA rapid guidance on the use of statins for primary prevention of cardiovascular disease in people living with HIV v2.
  9. R Collins et al; Interpreting the evidence for the efficacy and safety of statin therapy. Lancet 2016; 388:2532-61.
  10. Cannon CP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387–2397
  11. Amarenco P, et al. A comparison of two LDL cholesterol targets after ischemic stroke. N Engl J Med. 2020;382:9–19.
  12. Turgeon RD, et al. Does ezetimibe modify clinical outcomes? Can Fam Physician. 2015;61(3):251.
  13. Kim BK, et al. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. Lancet. 2022;400(10349):380–390.
  14. Nissen SE, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. 2023;388:1353–1364.
  15. Bhatt DL, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11–22.
  16. Sabatine MS, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713–1722.
  17. Schwartz GG, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379:2097–2107.
  18. Kolber MR, et al. Do PCSK9 inhibitors reduce cardiovascular events? Can Fam Physician. 2018;64(9):669

 

Lipid management V1.1 approved by Integrated Medicines Optimisation Committee (IMOC) May 2026