lipid lowering therapy in primary prevention of cardiovascular disease (CVD)

Last edited 06/2023 and last reviewed 06/2023

Before starting statin treatment perform baseline blood tests and clinical assessment, and treat comorbidities and secondary causes of dyslipidaemia. Include all of the following in the assessment:

• smoking status
• alcohol consumption
• blood pressure
• body mass index or other measure of obesity
• total cholesterol, non-HDL cholesterol, HDL cholesterol and triglycerides
• HbA1c
• renal function and eGFR
• transaminase level (alanine aminotransferase or aspartate aminotransferase)
• thyroid-stimulating hormone

Full formal risk assessment

• Click here for an online Qrisk calculator (QRISK3)

  • Hippisley-Cox et al developed first QRISK model to estimate 10 year risk of cardiovascular disease was published in 2007
    • was followed by an updated model (QRISK2) in 2008, which included ethnic origin and additional risk factors (type 2 diabetes, rheumatoid arthritis, atrial fibrillation, and chronic renal disease)
    • updated algorithms (QRISK3) quantify the absolute risks of CVD in people aged 25-84, which include established and new risk factors
    • new factors are an expanded definition of chronic kidney disease (stage 3, 4, or 5), migraine, corticosteroid use, systemic lupus erythematosus, atypical antipsychotic use, severe mental illness, erectile dysfunction, and a measure of blood pressure variability (standard deviation of repeated measures)
    • study authors concluded:
      • developed updated algorithms (QRISK3) to quantify absolute risks of cardiovascular disease in people aged 25-84 years, which include established risk factors and new risk factors:
        • expanded definition of chronic kidney disease (stage 3, 4, or 5),
        • migraine,
        • corticosteroid use,
        • SLE,
        • atypical antipsychotic use,
        • severe mental illness,
        • erectile dysfunction, and
        • a measure of blood pressure variability (standard deviation of repeated measures
      • updated risk algorithms provide valid measures of absolute risk in the general population of patients, as shown by the performance in a separate validation cohort
        
        
  • NICE suggest the use of QRISK3 in assessment risk of cardiovascular disease in the primary prevention setting (2)
    • use the QRISK3 tool to calculate the estimated CVD risk within the next 10 years for people aged between 25 and 84 without CVD
    • use
    • do not use a risk assessment tool for people who are at high risk of CVD, including people with:
      • type 1 diabetes (see the section on primary prevention of CVD for people with type 1 diabetes)
      • an estimated glomerular filtration rate less than 60 ml/min/1.73 m2 and/or albuminuria the QRISK3 tool for people with type 2 diabetes aged between 25 and 84
      • familial hypercholesterolaemia or other inherited disorders of lipid metabolism
    • recognise that CVD risk tools may underestimate risk in certain groups of people, including but not limited to:
      • people treated for HIV
      • people already taking medicines to treat CVD risk factors
      • people who have recently stopped smoking
      • people taking medicines that can cause dyslipidaemia such as immunosuppressant drugs
      • people with severe mental illness
      • people with autoimmune disorders, and other systemic inflammatory disorders
    • consider people aged 85 or older to be at increased risk of CVD because of age alone, particularly people who smoke or have raised blood pressure
    • consider using a lifetime risk tool such as QRISK3-lifetime to inform discussions on CVD risk and to motivate lifestyle changes, particularly for people with a 10-year QRISK3 score less than 10%, and people under 40 who have CVD risk factors
      
      
  • lipid modification therapy for the primary and secondary prevention of CVD
    • before starting lipid modification therapy for the primary prevention of CVD, take at least 1 lipid sample to measure a full lipid profile
      • should include measurement of total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, and triglyceride concentrations (fasting sample is not required)
    • atorvastatin 20 mg should be offered for the primary prevention of CVD to people who have a 10% or greater 10-year risk of developing CVD. Estimate the level of risk using the QRISK3 assessment tool
      • do not rule out treatment with atorvastatin 20 mg for the primary prevention of CVD just because the person's 10-year QRISK3 score is less than 10% if they have an informed preference for taking a statin or there is concern that risk may be underestimated
      • for people aged 85 and older consider treatment with atorvastatin 20 mg. Be aware of factors that may make treatment inappropriate
        • take into account additional factors such as potential benefits from lifestyle changes, informed patient preference, comorbidities, polypharmacy, general frailty and life expectancy
    • if a person has CVD then start statin treatment in people with CVD with atorvastatin 80 mg . A lower dose of atorvastatin if any of the following apply:
      • potential drug interactions
      • high risk of adverse effects
      • patient preference
        
        
  • target cholesterol level
    • measure total cholesterol, HDL cholesterol and non-HDL cholesterol in all people who have been started on high-intensity statin treatment at 3 months of treatment and aim for a greater than 40% reduction in non-HDL cholesterol. If a greater than 40% reduction in non-HDL cholesterol is not achieved:
      • discuss adherence and timing of dose
      • optimise adherence to diet and lifestyle measures
      • consider increasing dose if started on less than atorvastatin 80 mg and the person is judged to be at higher risk because of comorbidities, risk score or using clinical judgement

European guidance states (3):

• is recommended that a high-intensity statin is prescribed up to the highest tolerated dose to reach the LDL-C goals set for the specific risk group
• an ultimatec LDL-C goal of <1.4 mmol/L (55 mg/ dL) and LDL-C reduction of >50% from baseline should be considered in apparently healthy persons
  <70 years at very high risk
• an ultimate LDL-C goal of <1.8 mmol/L (70 mg/dL) and LDL-C reduction of >50% from baseline should be considered in apparently healthy persons <70 years at high risk
• in patients with established ASCVD, lipid-lowering treatment with an ultimatec LDL-C goal of <1.4 mmol/L (55 mg/dL) and a >50% reduction in LDLC vs. baseline is recommended
• if the goals are not achieved with the maximum tolerated dose of a statin, combination with ezetimibe is recommended
• for primary prevention patients at very high risk, but without FH, if the LDL-C goal is not achieved on a maximum tolerated dose of a statin and ezetimibe, combination therapy including a PCSK9 inhibitor may be considered
• for secondary prevention patients not achieving their goals on a maximum tolerated dose of a statin and ezetimibe, combination therapy including a PCSK9 inhibitor is recommended
• for very-high-risk FH patients (that is, with ASCVD or with another major risk factor) who do not achieve their goals on a maximum tolerated dose of a statin and ezetimibe, combination therapy including a PCSK9 inhibitor is recommended
• if a statin-based regimen is not tolerated at any dosage (even after rechallenge), ezetimibe should be considered
• if a statin-based regimen is not tolerated at any dosage (even after rechallenge), a PCSK9 inhibitor added to ezetimibe may be considered
• if the goal is not achieved, statin combination with a bile acid sequestrant may be considered
• statin therapy is not recommended in premenopausal female patients who are considering pregnancy or are not using adequate contraception
• Key:
  • ASCVD = atherosclerotic cardiovascular disease; FH = familial hypercholesterolaemia;
  • LDL-C = low-density lipoprotein cholesterol; PCSK9 = proprotein convertase subtilisin/kexin type 9

Fibrates for preventing CVD

• 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 acid for preventing CVD

• do not offer nicotinic acid (niacin) 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

Bile acid sequestrants (anion exchange resins) for preventing CVD

• doo not offer a bile acid sequestrant (anion exchange resin) 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

   

Omega-3 fatty acid preparations for preventing CVD

• doo not offer omega-3 fatty acid compounds 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

Combination therapy for preventing CVD

• do not offer the combination of a bile acid sequestrant (anion exchange resin), fibrate, nicotinic acid or omega-3 fatty acid compound with a statin for the primary or secondary prevention of CVD

ezetimibe

• prescribe in line with NICE guidance - see linked item

Reference:

• (1) Hippisley-Cox J, Coupland C, Brindle P. Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study. BMJ. 2017 May 23;357:j2099. doi: 10.1136/bmj.j2099. PMID: 28536104; PMCID: PMC5441081.
• (2) NICE (May 2023). Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease
• (3) Visseren FLJ et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. European Heart Journal (2021) 42, 32273337