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Lipid modification - primary and secondary CVD prevention - Management
Which first-line lipid modification therapy is recommended for secondary prevention?

  • Prescribe a statin, unless this is contraindicated.
  • Simvastatin 40 mg daily is the first-line choice.
  • Consider a lower dose of simvastatin or an alternative statin (e.g. pravastatin 40 mg daily) if there are potential drug interactions or simvastatin 40 mg is contraindicated (e.g. renal impairment).
  • Higher intensity statin therapy (simvastatin 80 mg or atorvastatin 80 mg) should only be considered first-line for people with acute coronary syndrome. Treatment should be initiated in secondary care.
Clarification / Additional information
  • Higher intensity statins are those that produce greater cholesterol lowering than simvastatin 40 mg (e.g. simvastatin 80 mg).
  • For information on the use of omega-3 fatty acids in people who have had a myocardial infarction within 3 months, and who are not achieving an intake of 7 g of omega-3 fatty acids per week in their diet, see Cardioprotective diet in the CKS topic on CVD risk assessment and management.
Basis for recommendation
  • The recommendation by the National Institute of Health and Clinical Excellence (NICE) to offer statins for secondary prevention is based on an earlier NICE Technology Appraisal of statins for the prevention of cardiovascular events [NICE, 2006; NICE, 2008a].
  • Statins for secondary prevention:
    • When considering lipid modification therapy in secondary prevention, preference was given by NICE to drugs for which there is evidence in clinical trials of a beneficial effect on cardiovascular disease (CVD) morbidity and mortality.
    • Statins are recommended first-line for the secondary prevention of CVD because there is good evidence from a meta-analysis, undertaken by NICE, which found statin therapy was associated with a reduction in all-cause mortality, CVD mortality, coronary heart disease (CHD) mortality, fatal myocardial infarction (MI), and coronary revascularization, when compared with placebo, in people with coronary heart disease.
    • Model studies undertaken by NICE showed a high probability (greater than 85%) that statin therapy is cost effective for all people with a history of CHD.
  • Safety of statin therapy:
    • NICE found good safety data to support the use of statins [National Collaborating Centre for Primary Care, 2008a]:
      • Evidence from two large meta-analyses indicates that serious muscular (e.g. rhabdomyolysis, myopathy) and liver (e.g. abnormal liver function tests) adverse effects are infrequent with statin therapy.
      • Evidence from another meta-analysis (involving 86,936 participants) found statins to have a neutral effect on cancer and cancer death risks. No type of cancer was affected by statin use and no subtype of statin affected the risk of cancer.
  • Treatment initiation — low intensity versus high intensity statin therapy:
    • Low intensity statin therapy is recommended for people with stable coronary artery disease because it is more likely to be more cost effective than high intensity statin therapy:
      • Cost effectiveness analysis undertaken by the NICE Guidance Development Group indicated that, when compared with low intensity statins (simvastatin 40 mg), high intensity statins (atorvastatin 80 mg) were not cost effective in people with stable coronary artery disease. The probability that high intensity statins are cost effective is about 42% when compared with low intensity statins.
      • Results from another cost effectiveness study undertaken by NICE indicate that the majority of people (69%) will reach a target of 5 mmol/L on simvastatin 40 mg. With a target of 4 mmol/L, 31% of people will reach this target on simvastatin 40 mg.
    • However, higher intensive statin therapy is preferred for people with acute coronary syndrome (ACS) because it is more likely to be more cost effective than low intensity statin therapy:
      • Modelling studies undertaken by NICE find fewer cardiovascular events occur in the population treated with higher intensity statins than with low intensity statins. The studies indicate a high probability (about 94%) that high intensity statins (both simvastatin and atorvastatin 80 mg) are cost effective in people with ACS.
      • Effectiveness data of higher intensive statin therapy for ACS patients were drawn from two studies (one involving simvastatin [de Lemos et al, 2004] and the other with atorvastatin [Cannon et al, 2004]) which were meta-analysed.
  • Pravastatin:
    • Pravastatin is recommended as an alternative to simvastatin because, unlike simvastatin, it is not significantly metabolized by cytochrome P450 isoenzymes.
    • A dose of pravastatin 40 mg daily is recommended because, in all preventive morbidity and mortality trials, this was the only studied starting and maintenance dose [ABPI Medicines Compendium, 2005b].

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