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Lipid modification - primary and secondary CVD prevention - Management
When should I consider intensifying lipid modification therapy for secondary prevention of cardiovascular disease?

  • Consider higher intensity lipid modification therapy if total cholesterol of less than 4 mmol/L or low-density lipoprotein (LDL) cholesterol of less than 2 mmol/L has not been achieved.
  • Any decision to offer a higher intensity statin should take into account patient preference and tolerability, comorbidities, multiple drug therapy, and the benefits and risks of treatment.
  • A target total cholesterol level of less than 5 mmol/L should be used as the minimum standard of care for all people with cardiovascular disease. Wherever possible, the optimal treatment targets should be achieved.
Basis for recommendation
  • These recommendations are based on guidance issued by the National Institute for Health and Clinical Excellence [NICE, 2008a].
  • Advantages and disadvantages of targets:
    • These were considered by the NICE Guidance Development Group (GDG) [National Collaborating Centre for Primary Care, 2008a]. For further information, see evidence on lipid targets for secondary prevention.
    • The NICE GDG concluded that, for most people, a target can be helpful in guiding increases of lipid-modifying drugs as long as it is clear that this target is intended to guide treatment rather than be a level that all people are expected to achieve.
    • For audit purposes, a target total cholesterol of less than 5 mmol/L is recommended to assess progress in populations or groups of people with cardiovascular disease, in recognition that more than a half of people will not achieve a total cholesterol of less than 4 mmol/L or low-density lipoprotein cholesterol of less than 2 mmol/L. This audit standard is the minimum standard of care for all high-risk people. Wherever possible, the optimal treatment targets should be achieved.
  • Clinical evidence and safety of higher intensity statin therapy:
    • This was reviewed by the NICE GDG [National Collaborating Centre for Primary Care, 2008a].
    • A meta-analysis of four randomized controlled trials in people with coronary heart disease (CHD) found that, compared with lower intensity statin therapy, higher intensity statin therapy was associated with a reduction in the composite outcome of coronary death or myocardial infarction (MI), and with a reduction in the composite outcome of coronary death or any cardiovascular event (MI, stroke, hospitalization for unstable angina, or any revascularization).
      • Higher intensity statin therapy was not associated with a reduction in all-cause mortality but there was a trend for significance in cardiovascular mortality compared with lower intensity statin therapy.
    • Evidence from four large trials and one retrospective study found that higher intensity statin therapy was associated with an increased risk of elevated liver enzymes than lower intensity therapy, but not with a significant increase in clinical liver diseases.
      • Higher intensity statin therapy with atorvastatin 80 mg daily (3 RCTs and one retrospective study) was not associated with an increase in rhabdomyolysis compared with lower intensity therapy.
      • Higher intensity statin therapy with simvastatin 80 mg daily (1 RCT) was associated with a small increase in rhabdomyolysis (0.13%) compared with simvastatin 20 mg daily (0%) [de Lemos et al, 2004].
      • The results of a subsequent RCT using simvastatin 80 mg daily, the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) trial [Clinical Trial Service Unit, 2008] also found a small increased risk of myopathy with simvastatin 80 mg (0.9%) compared with simvastatin 20 mg (0.02%). The Medicines and Healthcare products Regulatory Agency (MHRA) has recently reviewed these data and advised that simvastatin 80 mg 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 [MHRA, 2010].

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