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Lipid modification - primary and secondary CVD prevention - Management
What are the adverse effects of statins?

  • Statin intolerance is common. It is thought to affect around 5 to 10% of people taking a statin [Ara et al, 2008; Nair et al, 2008].
    • Statin intolerance is defined by the National Institute for Health and Clinical Excellence as the presence of clinically significant adverse effects from statin therapy that are considered to represent an unacceptable risk to the patient or that may result in compliance with therapy being compromised [NICE, 2007].
    • These adverse effects include new-onset muscle pain (often associated with levels of muscle enzymes in the blood indicative of muscle damage), significant gastrointestinal disturbance or alterations of liver function tests.
    • For people intolerant of a particular statin, there is very limited evidence from a small retrospective study (n = 40) which indicates switching to a different statin may be helpful — particularly from a lipophilic statin (e.g. simvastatin, atorvastatin, or fluvastatin) to a more water soluble (hydrophilic) statin (e.g. pravastatin or rosuvastatin) [Nair et al, 2008].
  • Serious muscular adverse effects are rare.
  • Headache and gastrointestinal adverse effects are common.
    • Headache has been reported as an adverse effect of all statins in clinical trials.
    • Gastrointestinal adverse effects include abdominal pain, flatulence, constipation, diarrhoea, and nausea and vomiting. These usually settle with time.
  • Other less common adverse effects include:
    • Sleep disturbances, including insomnia and nightmares:
      • The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that sleep disturbances are likely to be a class effect of all statins [MHRA, 2009b].
      • Postmarketing data suggest that sleep disturbances have commonly been reported with atorvastatin and fluvastatin [MHRA, 2009c]. Post marketing reports have also been received with pravastatin, simvastatin, and rosuvastatin, but it is not possible to determine whether there is any statin with which sleep disturbances are least likely.
      • Experts have previously suggested that a hydrophilic statin (pravastatin, fluvastatin, or rosuvastatin) may be less likely to cause sleep disturbance because it would be less likely to cross the blood-brain barrier than a lipophilic statin (simvastatin or atorvastatin) [Chong, 2002].
    • Memory loss
      • The MHRA has advised that memory loss is likely to be a class effect of all statins [MHRA, 2009b].
      • When assessing someone with memory loss, consider whether a statin could be the cause or a contributing factor.
      • With the exception of rosuvastatin, which had a higher incidence rate (3.0 cases per 1000 patient-years with rosuvastatin compared with 0 cases with placebo), the incidence rates of memory loss with statin use compared to placebo were similar. However, because there was insufficient information regarding confounding factors, causality with all statins cannot be ruled out because all statins have post-marketing reports of memory loss reoccurring after re-challenge with statin [MHRA, 2009c].
    • Sexual dysfunction
      • The MHRA has advised that sexual dysfunction is likely to be a class effect of all statins [MHRA, 2009b].
      • A case-control study reported that 12.1% of patients receiving lipid-lowering therapy reported erectile dysfunction compared with 5.6% of controls [Bruckert et al, 1996; MHRA, 2009c].
      • People should be directly questioned about whether they are having sexual problems because this adverse effect is often not volunteered because of embarrassment.
    • Depression
      • The MHRA has advised that depression may be a class effect of all statins [MHRA, 2009b].
      • Consider whether a statin may be a contributing factor in someone presenting with depression.
      • Atorvastatin and rosuvastatin had a higher incidence rate of depression compared with placebo in clinical trials. Although a direct causal link between other statins and depression could not be established, the MHRA identified one study that suggested that depression may be related to low levels of cholesterol, which suggests that causality cannot be ruled out [MHRA, 2009c].
  • Other rare adverse effects of statins include:
    • Peripheral neuropathy
      • Peripheral neuropathy has rarely been reported.
      • It is usually reversible on stopping treatment. NICE recommends that statins should be discontinued and specialist advice sought if a person develops an unexplained peripheral neuropathy [National Collaborating Centre for Primary Care, 2008a].
    • Interstitial lung disease
      • It is difficult to establish whether there is a causal relationship between statins and interstitial lung disease because this is a very rare adverse event [MHRA, 2009c].
      • However, the MHRA has issued the following advice because interstitial lung disease is a potentially life-threatening adverse reaction: 'people on statins should be advised to seek medical advice if they develop presenting features of interstitial lung disease such as dyspnoea, non-productive cough, and deterioration in general health (e.g. fatigue, weight loss, and fever)' [MHRA, 2009b].
    • Skin rashes and hair loss

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