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Lipid Management

    • Important instructions and notes - please click to read.

      Instructions: Click the links (blue text), icons () and drop-downs (▶) for further information. Select the appropriate clinical scenario to adjust the pathway.

      This is an adapted version of the source material referenced/linked below. Please see the original source for full details.

      Please read our medical disclaimer - this pathway may not be suitable for your particular patient or healthcare setting/system.
      If you would like to commission a more appropriate localised pathway please get in touch.

      This pathway is adapted from NHSE: Summary of National Guidance for Lipid Management for Primary and Secondary Prevention of CVD and Statin Intolerance Pathway


      INITIAL CONSIDERATIONS AND BASELINE MEASUREMENTS: ← click to view
      • Measure non-fasting full lipid profile (Total cholesterol, HDL-C, non-HDL-C, LDL-C, triglycerides), BMI and consider secondary causes of hyperlipidaemia and manage as needed.
        • In addition to full lipid profile, measure renal, thyroid and liver profiles (including albumin) and HbA1c to exclude secondary causes and co-morbidities.
        • Measure baseline liver transaminase (ALT or AST) before starting a statin.
        • Measure CK if unexplained muscle pain before starting a statin - CK should not be measured routinely especially if a patient is asymptomatic.
      • Identify and exclude people with contraindications/drug interactions.
      • Manage non-fasting triglyceride above 4.5mmol/L <div class="navybox"> <p><b><u>TRIGLYCERIDES</u> <br>Triglyceride concentration:</b></p> <ul> <li><b>4.5 - 9.9mmol/L</b> <ul> <li>If non-fasting triglycerides are greater than 4.5mmol/L, repeat with a fasting TG measurement. Be aware that the CVD risk may be underestimated by risk assessment tools, optimise the management of other CVD risk factors present and seek specialist advice if nonHDL-C concentration is > 7.5 mmol/litre.</li> </ul> </li> <li><b>10 - 20mmol/L</b> <ul> <li>Repeat the TG measurement with a fasting test (after an interval of 5 days, but within 2 weeks) and review for potential secondary causes of hyperlipidaemia. Seek specialist advice if the TG concentration remains &gt; 10mmol/litre. At risk of acute pancreatitis.</li> </ul> </li> <li><b>Greater than 20mmol/L</b> <ul> <li><b>Refer to lipid clinic for urgent specialist review</b> if not a result of excess alcohol or poor glycaemic control. At risk of acute pancreatitis.</li> </ul> </li> </ul> </div> .

    • ↓

    • Using the QRISK®3 risk calculator where appropriate, consider statin therapy for adults who do not have established CVD but fall into the following categories:

      • Age ≤ 84 & QRISK ≥ 10% over next 10 years
      • Type 2 diabetes & QRISK ≥ 10% over next 10 years
      • <div class="navybox"> While NICE recommends offering statins to patients with Type 1 diabetes as detailed below, it also states to consider statins in all adults with type 1 diabetes. </div> , if they have one or more of the following:
        • Over 40 years
        • Had diabetes for > 10 years
        • Have established nephropathy
        • Have other CVD risk factors
      • CKD eGFR < 60 mL/min/1.73m2 and/or albuminuria
      • Age ≥ 85 years if appropriate consider comorbidities, frailty & life expectancy

      ↓

      Identify and address all modifiable risk factors
      smoking, diet, obesity, alcohol intake, physical activity, blood pressure and HbA1c

      ↓

      Consider <div class="navybox"> <p><b><u>Additional Risk Factors</u></b></p> <p>Note, standard CVD risk scores including QRISK may underestimate risk in people who have additional risk because of underlying medical conditions or treatments. These groups include the following groups of people:</p> <ul> <li>severe obesity (BMI &gt; 40kg/m<sup>2</sup>) increases CVD risk</li> <li>treated for HIV</li> <li>serious mental health problems</li> <li>taking medicines that can cause dyslipidaemia such as antipsychotic medication, corticosteroids or immunosuppressant drugs</li> <li>autoimmune disorders such as systemic lupus erythematosus, and other systemic inflammatory disorders</li> <li>impaired fasting glycaemia</li> <li>significant hypertriglyceridaemia (fasting triglycerides 4.5-9.9mmol/L)</li> <li>recent risk factor changes e.g. quit smoking, BP or lipid treatment </li> </ul> <p>Consider socio-economic status as an additional factor contributing to CVD risk.</p> <div class="greybox" style="text-align:center;"> <p><b>If QRISK &lt; 10% over the next 10 years - Give lifestyle advice and ensure regular review of CVD risk in line with guidance.</b></p> </div> </div> , if present, together with QRISK score

      ↓

      If lifestyle modification is ineffective or inappropriate offer statin treatment.
      Atorvastatin 20mg OD

      ↓

      Aim for a > 40% reduction in baseline <b>Non-HDL-C</b> = TC minus HDL-C

      Post-treatment blood tests and monitoring

      Repeat full lipid profile (non-fasting) at 3 months

      • Provide annual medication reviews for people taking statins to discuss effectiveness of therapy, medicines adherence, lifestyle modification and address CVD risk factors.
      • Consider an annual non-fasting full lipid profile to inform the discussion around effectiveness of lipid lowering therapy and any medicines non-adherence.

      Measure liver transaminase within 3 months of starting treatment and then within 3 months of every additional up titration and then again at 12 months, but not again unless clinically indicated.

      • If ALT or AST are greater than 3 times the upper limit of normal then do not initiate a statin or discontinue statin therapy already prescribed and repeat the LFTs in a month.
      • If ALT or AST are elevated but are less than 3 times the upper limit of normal then:
        • Continue the statin and repeat in a month.
        • If they remain elevated but are less than 3 times the upper limit of normal then continue statin and repeat again in 6 months.
      Notes and Action if treatment target not achieved or treatment side-effects

      <div class="navybox"> <img src="https://productivemedic.com/wp-content/uploads/2021/04/Statin-Intensity-Table.png" alt=""> <p style="text-align:right;"><a href="https://www.england.nhs.uk/aac/wp-content/uploads/sites/50/2020/04/lipid-management-pathway-guidance.pdf" target="_blank">Source PDF</a></p> </div> treatment should achieve reduction of non-HDL-C > 40% from baseline. If not achieved after 3 months;

      • discuss treatment adherence, timing of dose, diet and lifestyle
      • if at higher risk (based on comorbidities, risk score or clinical judgement) consider increasing the dose every 2-3 months up to a maximum dose of atorvastatin 80mg OD.
      • For patients with Chronic Kidney Disease (eGFR less than 60 mL/min/1.73m2 and/or albuminuria)
        • Increase the dose if a greater than 40% reduction in non-HDL-C is not achieved and eGFR is 30 mL/min/1.73m2 or more.
        • Agree the use of higher doses with a renal specialist if eGFR is less than 30 mL/min/1.73m2

      ↓

      • If patients on a high‑intensity statin have side effects, offer a lower dose or an <div class="navybox"> <img src="https://productivemedic.com/wp-content/uploads/2021/04/Statin-Intensity-Table.png" alt=""> <p style="text-align:right;"><a href="https://www.england.nhs.uk/aac/wp-content/uploads/sites/50/2020/04/lipid-management-pathway-guidance.pdf" target="_blank">Source PDF</a></p> </div>
      • If maximum tolerated dose of statin does not achieve non-HDL-C reduction > 40% of baseline value after 3 months consider adding Ezetimibe 10mg OD (NICE TA385)
      • If recommended statin therapy is contraindicated or not tolerated;
        • Ezetimibe monotherapy may be considered. Assess response after 3 months
        • See local statin intolerance guidance / pathway where available

      ↓

      If non-HDL-C reduction remains < 40% of baseline despite maximal tolerated lipid lowering therapy (including people with intolerances and contraindications) consider referral to specialist lipid management clinic according to local arrangements

    • Offer statin therapy to adults with CVD
      this includes angina, previous MI, revascularisation, stroke or TIA or symptomatic peripheral arterial disease.
      Do not delay statin treatment if a person has acute coronary syndrome. Take a lipid sample on admission (within 24 hours)

      ↓

      Identify and address all modifiable risk factors
      smoking, diet, obesity, alcohol intake, physical activity, blood pressure and HbA1c

      ↓

      Do not delay statin treatment in secondary prevention while managing modifiable risk factors.
      Prescibe a high intensity statin:
      Atorvastatin 80mg OD

      Use a lower dose of Atorvastatin if there is a potential drug interaction, high risk of or experiencing adverse effects, or patient preference.

      Offer Atorvastatin 20mg if CKD (people with GFR < 60 mL/min/1.73m2).

      ↓

      Aim for a > 40% reduction in <div class="navybox"> <p>If baseline cholesterol is unknown in the setting of secondary prevention use the Joint British Societies’ JBS3 consensus recommendation:</p> <ul> <li><b>non-HDL-C &lt; 2.5mmol/L (LDL-C &lt; 1.8mmol/L)</b> <ul> <li>Non-HDL-C = TC minus HDL-C</li> <li>LDL-C = non-HDL-C minus (Fasting triglycerides/2.2) - valid only when fasting triglycerides are less than 4.5 mmol/L </li> </ul> </li> </ul> </div>

      Post-treatment blood tests and monitoring

      Repeat full lipid profile (non-fasting) at 3 months

      • Provide annual medication reviews for people taking statins to discuss effectiveness of therapy, medicines adherence, lifestyle modification and address CVD risk factors.
      • Consider an annual non-fasting full lipid profile to inform the discussion around effectiveness of lipid lowering therapy and any medicines non-adherence.

      Measure liver transaminase within 3 months of starting treatment and then within 3 months of every additional up titration and then again at 12 months, but not again unless clinically indicated.

      • If ALT or AST are greater than 3 times the upper limit of normal then do not initiate a statin or discontinue statin therapy already prescribed and repeat the LFTs in a month.
      • If ALT or AST are elevated but are less than 3 times the upper limit of normal then:
        • Continue the statin and repeat in a month.
        • If they remain elevated but are less than 3 times the upper limit of normal then continue statin and repeat again in 6 months.
      Notes and Action if treatment target not achieved or treatment side-effects

      <div class="navybox"> <img src="https://productivemedic.com/wp-content/uploads/2021/04/Statin-Intensity-Table.png" alt=""> <p style="text-align:right;"><a href="https://www.england.nhs.uk/aac/wp-content/uploads/sites/50/2020/04/lipid-management-pathway-guidance.pdf" target="_blank">Source PDF</a></p> </div> treatment should achieve reduction of non-HDL-C > 40% from baseline. If not achieved after 3 months:

      • discuss treatment adherence, timing of dose, diet and lifestyle measures
      • if started on less than atorvastatin 80mg and the person is judged to be at higher risk (based on comorbidities, risk score or clinical judgement) consider increasing to a maximum dose of atorvastatin 80mg OD.
      • For patients with Chronic Kidney Disease (eGFR less than 60 mL/min/1.73m2 and/or albuminuria)
        • Increase the dose if a greater than 40% reduction in non-HDL-C is not achieved and eGFR is 30 mL/min/1.73m2 or more.
        • Agree the use of higher doses with a renal specialist if eGFR is less than 30 mL/min/1.73m2
      • If non-HDL-C baseline value is not available, use target non-HDL-C < 2.5mmol/L (approximately equivalent to LDL-C < 1.8mmol/L) as recommended by JBS3 consensus statement - a ‘lower is better approach’

      ↓

      • If patients on a high‑intensity statin have side effects, offer a lower dose or an <div class="navybox"> <img src="https://productivemedic.com/wp-content/uploads/2021/04/Statin-Intensity-Table.png" alt=""> <p style="text-align:right;"><a href="https://www.england.nhs.uk/aac/wp-content/uploads/sites/50/2020/04/lipid-management-pathway-guidance.pdf" target="_blank">Source PDF</a></p> </div>
      • If maximum tolerated dose of statin does not achieve non-HDL-C reduction > 40% of baseline value and/or non-HDL-C < 2.5mmol/L after 3 months consider adding Ezetimibe 10mg OD (NICE TA385)
      • If recommended statin therapy is contraindicated or not tolerated;
        • Ezetimibe monotherapy may be considered. Assess response after 3 months
        • See local statin intolerance guidance / pathway where available

      ↓

      If non-HDL-C > 4.0mmol/L despite maximal tolerated lipid lowering therapy (including people with intolerances and contraindications), arrange a fasting blood test for LDL-C measurement and if <div class="navybox"> <img src="https://productivemedic.com/wp-content/uploads/2021/04/Lipid-Specialist-services.png" alt=""> <p style="text-align:right;"><a href="https://www.england.nhs.uk/aac/wp-content/uploads/sites/50/2020/04/lipid-management-pathway-guidance.pdf" target="_blank">Source PDF</a></p> </div> are met, refer for confirmation and initiation of PCSK9i (NICE TA 393, 394) according to local arrangements

    • SEVERE HYPERLIPIDAEMIA

      If TC > 7.5mmol/L and/or LDL-C > 4.9mmol/L and/or non-HDL-C > 5.9mmol/L, a personal and/or family history of confirmed CHD ( < 60 years) and with no secondary causes:

      • suspect Familial Hypercholesterolaemia (Possible Heterozygous Familial Hypercholesterolaemia)

      Do not use QRISK risk assessment tool.

      ↓

      DIAGNOSIS AND REFERRAL

      Take fasting blood for repeat lipid profile to measure LDL-C.

      Use the Simon Broome or Dutch Lipid Clinic Network (DLCN) criteria to make a clinical diagnosis of Familial Hypercholesterolaemia.

      Refer to Lipid Clinic for further assessment if:

      • clinical diagnosis of Familial Hypercholesterolaemia or
      • if TC > 9.0mmol/L and/or LDL-C > 6.5mmol/L and/or non-HDL-C > 7.5mmol/L or
      • Fasting triglycerides > 10mmol/L <div class="navybox"> <p><b><u>TRIGLYCERIDES</u> <br>Triglyceride concentration:</b></p> <ul> <li><b>4.5 - 9.9mmol/L</b> <ul> <li>If non-fasting triglycerides are greater than 4.5mmol/L, repeat with a fasting TG measurement. Be aware that the CVD risk may be underestimated by risk assessment tools, optimise the management of other CVD risk factors present and seek specialist advice if nonHDL-C concentration is > 7.5 mmol/litre.</li> </ul> </li> <li><b>10 - 20mmol/L</b> <ul> <li>Repeat the TG measurement with a fasting test (after an interval of 5 days, but within 2 weeks) and review for potential secondary causes of hyperlipidaemia. Seek specialist advice if the TG concentration remains &gt; 10mmol/litre. At risk of acute pancreatitis.</li> </ul> </li> <li><b>Greater than 20mmol/L</b> <ul> <li><b>Refer to lipid clinic for urgent specialist review</b> if not a result of excess alcohol or poor glycaemic control. At risk of acute pancreatitis.</li> </ul> </li> </ul> </div> (regardless of family history)

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      TREATMENT TARGETS IN Familial Hypercholesterolaemia

      If clinical diagnosis of Familial Hypercholesterolaemia and/or other risk factors present follow the recommended treatment management pathway for primary or secondary prevention as for non-Familial Hypercholesterolaemia, BUT Aim to achieve at least a 50% reduction of LDL-C (or non-fasting non-HDL-C) from baseline.

      Consider specialist referral for further treatment and/or <div class="navybox"> <img src="https://productivemedic.com/wp-content/uploads/2021/04/Lipid-Specialist-services.png" alt=""> <p style="text-align:right;"><a href="https://www.england.nhs.uk/aac/wp-content/uploads/sites/50/2020/04/lipid-management-pathway-guidance.pdf" target="_blank">Source PDF</a></p> </div> IF

      • they are assessed to be at very high risk of a coronary event - defined as any of the following:
        • Established coronary heart disease.
        • Two or more other CVD risk factors.
      • OR therapy is not tolerated
      • OR LDL-C remains > 5mmol/L (primary prevention)
      • OR LDL-C remains > 3.5mmol/L (secondary prevention)

      despite maximal tolerated statin and Ezetimibe therapy.

    • Person at high CVD risk reports potential intolerance to recommended high intensity statin treatment

      ↓

      New onset or worsening of muscle symptoms since starting statins? (pain, tenderness or weakness)

    • ↓

      Consider other potential side effects for statins

      • Be aware of <div class="navybox"> <p><b>Nocebo effect</b> is negative expectations of the patient regarding a treatment leading to reporting more negative effects even if they are prescribed a placebo.</p> </div> <div class="navybox"> <p><b>Statin reluctance</b> s an attitudinal state of aversion to taking statins (often without prior exposure).</p> </div>
      • <div class="navybox"> <p><b><u>Person-centred approach to address statin intolerance</u></b></p> <p><b>Initial Consultation</b></p> <ul> <li>Be aware of “nocebo effect” and “statin reluctance” <ul> <li><b>Nocebo effect</b> is negative expectations of the patient regarding a treatment leading to reporting more negative effects even if they are prescribed a placebo.</li> <li><b>Statin reluctance</b> s an attitudinal state of aversion to taking statins (often without prior exposure).</li> </ul> </li> <li>Reinforce healthy lifestyle habits (e.g. exercise, reducing weight)</li> <li>Listen to the concerns of each patient.</li> <li>Explain LDL-C targets and strategies to lower LDL-C/non-HDL-C</li> <li>Discuss options to reduce LDL-C/non-HDL-C with pros and cons</li> <li>Explain the benefits of statins</li> <li>Evaluate & identify any risk factors and address (e.g. drug interactions)</li> <li>Work with patients to identify and agree best options and next steps</li> </ul> <p><b>Follow up</b></p> <ul> <li>Follow up on agreed plan and address any issues/concern.</li> <li>Advise patients to contact you if they experience muscle symptoms</li> <li>Ongoing patient education and regular review helps addressing concerns around medicine safety and underline the importance of adherence.</li> </ul> </div>
      Non-muscle related statin side effects

      May vary between different statins. In clinical trials some side effects often associated with statins are not statistically different from placebo.

      Most commonly reported: gastrointestinal disturbance and asymptomatic increases in hepatic transaminases (ALT or AST). May affect up to 1 in 10 statin users.

      Rarer side effects include: Hepatotoxicity, new onset Type 2 Diabetes (benefits outweigh risk, do not stop statin), Renal insufficiency, proteinuria, Neurocognitive and neurological impairments (no apparent link from RCTs), Intracranial haemorrhage (conflicting evidence, benefit outweigh possible harm), Interstitial lung disease, Pancreatitis, Skin disorders including alopecia, Lupus-like reaction, Sleep disturbance, headache, dizziness, fatigue, depression, sexual dysfunction.

      Management: If symptoms appear statin related, consider de-challenge and re-challenge or change to a different statin (e.g. hydrophilic instead of lipophilic).

      Liver enzyme abnormalities - minor increases in liver enzymes (< 2x ULN) may be seen within the first three months of statin therapy; temporary discontinuation and further assessment is warranted if levels exceed 3x ULN. Several studies have confirmed that the cardiovascular benefits of statin treatment in high-risk populations outweigh the rare adverse effects, such as rhabdomyolysis.

      Symmetrical pain and/or weakness in large proximal muscle groups, worsened by exercise

      Risk factors for SRM and statin intolerance

      Endogenous factors

      • Female gender
      • Advanced age (> 75 yrs)
      • Frailty (reduced lean body mass)
      • History of muscle disorder or high CK
      • Impaired renal or hepatic function
      • Personal or Family history of intolerance to lipid-lowering therapies.
      • Hypothyroidism

      Exogenous Factors

      • Excessive alcohol intake
      • High intensity exercise
      • Dehydration
      • Drug interactions with statins (including herbal medicines)
      • Vitamin D deficiency

      Classification of statin related muscle toxicity (SRM)

      Source PDF

    • ↓

      Muscular symptoms not related to statins

      ↓

      Non SRM: Consider other causes e.g. PMR, Vit D deficiency. Check bone profile, Vit D, CRP.

    • Assess severity of symptoms +/- repeat baseline assessment*
      Consider other causes if new onset of muscle symptoms of > 2 weeks duration in a person previously tolerant of statin therapy for > 3 months

    • ↓

      Improvement within 2 weeks
      Resolved within 6 weeks
      Patient happy to continue

      ↓
      No

    • ↓

      Stop statin for 4-6 weeks
      Document time to symptom onset and time to resolution

    • ↓

      Stop statin and consider Rhabdomyolysis
      Urgently seek specialist advice and inpatient assessment

    • ↓

      Consider Statin induced necrotizing autoimmune myopathy (SINAM)
      Seek specialist advice and consider PCSK9i (NICE TA 393, 394)

    • ↓

      Non-SRM. Consider other causes

    • ↓

      Wait for 2 weeks before rechallenge

    • ↓

      Reassess and restart with lower dose / alternative statin - <div class="navybox"> <p><b><u>Statin-based approaches to manage muscle symptoms</u></b></p> <ul> <li>Adopt person-centred approach as described above.</li> <li>Therapy with a lower dose statin is preferred to no statin.</li> <li>Apply a repetitive “De-Challenge” - “Re-Challenge” approach to establish if symptoms are caused by a statin(s) and the best statin regimen for each patient.</li> <li>Switch to a different statin or re-challenge with the same statin using a lower dose or frequency (intermittent dosages).</li> <li>Patients who do not tolerate statins on a daily basis, alternate day or twice-weekly dosing is a good option.</li> <li>Rosuvastatin and atorvastatin have longer half-lives, permitting their use on a non-daily regime.</li> <li>Adding ezetimibe to a lower dose statin may be better tolerated with robust reduction of LDL-C / non-HDL-C.</li> <li>Once a new regime is tolerated, dose / frequency can be up-titrated slowly to achieve LDL-C / non-HDL-C goals with minimal or no muscle complaints.</li> </ul> <p style="text-align: center;"><em>It is important to note that cardiovascular benefits have not been proven for all the above approaches but any reduction of LDL-C / non-HDL-C is beneficial.</em></p> </div>
      Offer low or moderate dose of a higher intensity statin (Atorvastatin 10 or 20 mg OD, or Rosuvastatin 5 or 10mg OD)

    • ↓

      No recurrence of muscle symptoms
      Titrate at 8 weeks intervals to achieve appropriate targets

      ↓

      Symptoms tolerable
      Treatment goals achieved
      Patient happy to continue

      ↓
      No

    • ↓

      Recurrence of muscle symptoms
      Short time to onset
      Symptoms intolerable

    • ↓

      <div class="navybox"> <p><b><u>Statin-based approaches to manage muscle symptoms</u></b></p> <ul> <li>Adopt person-centred approach as described above.</li> <li>Therapy with a lower dose statin is preferred to no statin.</li> <li>Apply a repetitive “De-Challenge” - “Re-Challenge” approach to establish if symptoms are caused by a statin(s) and the best statin regimen for each patient.</li> <li>Switch to a different statin or re-challenge with the same statin using a lower dose or frequency (intermittent dosages).</li> <li>Patients who do not tolerate statins on a daily basis, alternate day or twice-weekly dosing is a good option.</li> <li>Rosuvastatin and atorvastatin have longer half-lives, permitting their use on a non-daily regime.</li> <li>Adding ezetimibe to a lower dose statin may be better tolerated with robust reduction of LDL-C / non-HDL-C.</li> <li>Once a new regime is tolerated, dose / frequency can be up-titrated slowly to achieve LDL-C / non-HDL-C goals with minimal or no muscle complaints.</li> </ul> <p style="text-align: center;"><em>It is important to note that cardiovascular benefits have not been proven for all the above approaches but any reduction of LDL-C / non-HDL-C is beneficial.</em></p> </div>
      (For example co-administering ezetimibe or as monotherapy)

      ↓
      If not effective

      Seek specialist advice and consider PCSK9i (NICE TA 393, 394)