Statin intolerance

This has been defined in the NICE guidance regarding use of ezetimibe (1):

• "...intolerance to initial statin therapy should be defined 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
  • adverse effects include evidence of 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.."
• in some circumstances a statin may still be able to be used - however often this situation will require expert advice
  • depends on the degree and type of statin associated side effect
  • if mild side effect e.g. myalgia without a significantly raised CK, then a change of statin might allow satisfactory control of lipid levels without a recurrence of intolerance
    • if a patient has muscle related side effects then a water-soluble (hydrophilic) statin might be substituted e.g. pravastatin
    • conversely raised in transaminases may be more problematic when hydrophilic statins are used aggressively in comparison to using a lipid-soluble (lipophilic) statin e.g. simvastatin
• ezetimibe (cholesterol uptake inhibitor) monotherapy is recommended as an option for the treatment of adults with primary (heterozygous-familial or non-familial) hypercholesterolaemia who would otherwise be initiated on statin therapy
• other treatment options are dependent on other factors e.g. significantly raised triglycerides and a low HDL might be treated with a fibrate
• intermittent statin therapy may be effective at lowering cholesterol but with no or lesser risk of side effects
  
  
• NICE state (3):
  • if a person is not able to tolerate a high-intensity statin aim to treat with the maximum tolerated dose
  • inform the person that any statin at any dose reduces CVD risk. If someone reports adverse effects when taking high-intensity statins discuss the following possible strategies with them:
    • stopping the statin and trying again when the symptoms have resolved to check if the symptoms are related to the statin
    • reducing the dose within the same intensity group
    • changing the statin to a lower intensity group
  • seek specialist advice about options for treating people at high risk of CVD such as those with CKD, type 1 diabetes, type 2 diabetes or genetic dyslipidaemias, and those with CVD, who are intolerant to 3 different statins. Advice can be sought for example, by telephone, virtual clinic or referral
• a review of 176 studies (112 RCTs and 64 cohort studies, n=4,143,517) found a prevalence of statin intolerance of 9.1% (4)
  • statin lipid solutbility did not affect prevalence, but age, female gender, diabetes, hypothyroidism and Asian or Black race were associated with statin intolerance

See linked management algorithm.

Reference:

• 1. NICE (November 2007). Ezetimibe for the treatment of primary (heterozygous-familial and non-familial) hypercholesterolaemia.
• 2. Dale KM et al. Impact of statin dosing intensity on transaminase and creatine kinase. Am J Med. 2007 Aug;120(8):706-12
• 3. NICE (July 2014). Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease
• 4. Bytyçi I et al, on behalf of the Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group and the International Lipid Expert Panel (ILEP), Prevalence of statin intolerance: a meta-analysis, European Heart Journal, 2022;, ehac015, https://doi.org/10.1093/eurheartj/ehac015