lipid lowering treatment for secondary prevention

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NICE state with respect to secondary prevention (1):

  • secondary prevention, lipid modification therapy should be offered and should not be delayed by management of modifiable risk factors. Blood tests and clinical assessment should be performed, and comorbidities and secondary causes of dyslipidaemia should be treated. Assessment should include:
    • smoking status
    • alcohol consumption
    • blood pressure
    • body mass index or other measure of obesity
    • fasting total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides (if fasting levels are not already available)
    • fasting blood glucose
    • renal function
    • liver function (transaminases)
    • thyroid-stimulating hormone (TSH) if dyslipidaemia is present
  • if a person has acute coronary syndrome, statin treatment should not be delayed until lipid levels are available. A fasting lipid sample should be taken about 3 months after the start of treatment

The landmark trials regarding the use of statins in secondary prevention are the 4S (Scandinavian Simvastatin Survival Study), the CARE (Cholesterol And Recurrent Events) trial and the LIPID (Long-term Intervention with Pravastatin in Ischaemic Heart Disease).

  • these trials revealed that reduction of total serum cholesterol and low-density lipoprotein (LDL) cholesterol in the region of 25-35% using statin therapy led to a reduction in coronary heart disease (CHD) mortality by approximately the same degree
  • the trial evidence was that patients with unstable angina benefited to the same degree as to those post - myocardial infarction

NICE suggest (1):

  • start statin treatment in people with CVD with atorvastatin 80 mg. Use a lower dose of atorvastatin if any of the following apply:

    • potential drug interactions
    • high risk of adverse effects
    • patient preference

  • Target
    • 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
    • Note that European guidance provides actual targets for primary and secondary prevention rather than percentage reduction of non-HDL cholesterol (2)
      • Targets from European guidance (2):

        The European guideline considers patients in terms of different levels of risk and targets reflect the different level of risk. The guidance states that '..in general, total plasma cholesterol should be <5 mmol/L (<190 mg/dL), and LDL cholesterol should be <3 mmol/L (<115 mg/dL). In subjects with higher CVD risk, the treatment goals should be lower

        Level of Risk Factors putting in this risk category Lipid lowering target
        Very high risk

        Subjects with any of the following:

        • documented CVD by invasive or non-invasive testing (such as coronary angiography, nuclear imaging, stress echocardiography, carotid plaque on ultrasound), previous myocardial infarction, ACS, coronary revascularization (PCI, CABG), and other arterial revascularization procedures, ischaemic stroke, peripheral artery disease (PAD)
        • diabetes mellitus (type 1 or type 2) with one or more CV risk factors and/or target organ damage (such as microalbuminuria: 30-300 mg/24 h)
        • severe chronic kidney disease (CKD) (GFR <30 mL/min/ 1.73 m2).
        • a calculated SCORE >= 10% (of fatal CVD event in next 10 years)
        LDL cholesterol goal is <1.8 mmol/L (less than 70 mg/dL) or a >=50% LDL cholesterol reduction when the target level cannot be reached.
        High risk

        Subjects with any of the following:

        • markedly elevated single risk factors such as familial dyslipidaemias and severe hypertension
        • diabetes mellitus (type 1 or type 2) but without CV risk factors or target organ damage
        • moderate chronic kidney disease (GFR 30-59 mL/min/1.73 m2).
        • calculated SCORE of >= 5% and <10% for 10-year risk of fatal CVD.
        LDL cholesterol goal <2.5 mmol/L (less than 100 mg/dL) should be considered
        Moderate risk Subjects are considered to be at moderate risk when their SCORE is >1 and <5% at 10 years. Many middle-aged subjects belong to this category. Risk may also be higher than indicated in the charts* LDL cholesterol goal <3.0 mmol/L (less than 115 mg/dL) should be considered
        Low Risk The low-risk category applies to individuals with a SCORE <1% and free of qualifiers that would put them at moderate risk. no target

        SCORE risk chart used in this guideline are not equivalent to QRISK2 as SCORE risk is based on the risk of a FATAL CVD event in the next 10 years. For more information about the SCORE charts then click here

        *Risk may also be higher than indicated in the charts in:

        • sedentary subjects and those with central obesity; these characteristics determine many of the other aspects of risk listed below. The increased risk associated with overweight is greater in younger subjects than in older subjects
        • socially deprived individuals and those from ethnic minorities.
        • individuals with diabetes: SCORE charts should be used only in those with type 1 diabetes without target organ damage. Risk rises with increasing blood sugar concentration before overt diabetes occurs
        • individuals with low HDL cholesterol, increased triglycerides, fibrinogen, apolipoprotein B (apoB), and lipoprotein(a) [Lp(a)] levels, especially in combination with familial hypercholesterolaemia, and perhaps increased high-sensitivity CRP (hsCRP). In particular, a low HDL level will indicate a higher level of risk in both sexes, all age groups, and at all levels of ris
        • asymptomatic individuals with preclinical evidence of atherosclerosis, for example plaque on carotid ultrasonography
        • those with moderate to severe chronic kidney disease [glomerular filtration rate (GFR) <60 mL/min/1.73 m2]
        • positive family history of premature CVD.

        HDL and triglycerides (2)

        • although low HDL cholesterol is an independent risk factor for CVD, no specific treatment goals are as yet defined, but may be considered at concentrations >1.0 mmol/L (40 mg/dL) in men and >1.2 mmol/L (45 mg/dL) in women. Similarly, fasting triglycerides should be <.1.7 mmol/L (150 mg/dL).

Notes:

  • Dose of particular statin versus reduction in LDL cholesterol

    Dose (mg/day) 5 10 20 40 80
    fluvastatin - - 21% a 27% a 33% b
    pravastatin - 20% a 24% a 29% a -
    simvastatin - 27% a 32% b 37% b 42% c,d
    atorvastatin - 37% b 43% c 49% c 55% c
    rosuvastatin 38% b 43% c 48% c 53% c -
    • a 20%- 30%: low intensity

    • b 31%- 40%: medium intensity

    • c Above 40%: high intensity

    • d Advice from the MHRA: there is an increased risk of myopathy associated with high-dose (80 mg) simvastatin. The 80 mg 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.
  • do not offer nicotinic acid analogues, bile sequestrants or omega3 fatty acid preparations for secondary prevention of CVD

  • do not routinely use fibrates for secondary prevention of CVD

  • 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 for secondary prevention
      • people with primary hypercholesterolaemia should be considered for ezetimibe treatment in line with NICE guidance - seee linked item

Reference:

Last reviewed 01/2018

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