NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient

J Clin Lipidol. 2022 Jul-Aug;16(4):361-375. doi: 10.1016/j.jacl.2022.05.068. Epub 2022 Jun 9.


Although statins are generally well tolerated, statin intolerance is reported in 5-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes. This Scientific Statement from the National Lipid Association was developed to provide an updated definition of statin intolerance and to inform clinicians and researchers about its identification and management. Statin intolerance is defined as one or more adverse effects associated with statin therapy which resolves or improves with dose reduction or discontinuation and can be classified as a complete inability to tolerate any dose of a statin or partial intolerance with inability to tolerate the dose necessary to achieve the patient-specific therapeutic objective. To classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest approved daily dosage. This Statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a "nocebo" effect (patient expectation of harm resulting in perceived side effects). To identify a tolerable statin regimen it is recommended that clinicians consider using several different strategies (e.g., different statin, dose, and/or dosing frequency). Non-statin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy. If so, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored. In high and very high risk patients who are statin intolerant, clinicians should consider initiating non-statin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins.

Keywords: Adherence; Atherogenic lipoproteins; Nocebo; Non-statin; Non-statin therapy; Persistence; Statin; Statin intolerance.

MeSH terms

  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / prevention & control
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
  • Nocebo Effect
  • Risk Factors
  • Risk Reduction Behavior


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors