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Resistance and intolerance to statins

Z Reiner1

  • 1Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia.

Nutrition, Metabolism, and Cardiovascular Diseases : NMCD
|July 6, 2014
PubMed
Abstract

Insights

Many patients struggle with statin therapy due to resistance or intolerance. Nonadherence is a common cause of poor low-density lipoprotein cholesterol (LDL-C) response, but alternative treatments exist.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacogenomics
  • Lipid Metabolism

Background:

  • Statin therapy is crucial for managing hypercholesterolemia.
  • A significant number of patients exhibit statin resistance, failing to achieve target low-density lipoprotein cholesterol (LDL-C) levels.
  • Statin intolerance, characterized by adverse effects like myopathy, further limits treatment efficacy.

Purpose of the Study:

  • To explore the genetic and non-genetic factors contributing to statin resistance and intolerance.
  • To identify potential biomarkers for predicting statin response.
  • To review alternative therapeutic strategies for patients unresponsive or intolerant to statins.

Main Methods:

  • Review of genetic polymorphisms associated with statin metabolism and efficacy.
  • Analysis of clinical factors influencing statin response, including inflammatory states and adherence.
  • Examination of current and emerging alternative lipid-lowering therapies.

Main Results:

  • Statin resistance is linked to genetic variations in genes involved in cholesterol synthesis, transport, and drug metabolism (e.g., HMG-CoA-R, ABCB1, ABCG2, OATP, NPC1L1, PCSK9, LDLR).
  • Nonadherence and non-persistence are identified as primary drivers of pseudo-statin resistance.
  • Inflammatory conditions and HIV infection can also diminish statin effectiveness.

Conclusions:

  • While numerous genetic factors are associated with statin response, routine pharmacogenetic testing is not yet recommended.
  • Addressing nonadherence is critical for optimizing statin therapy.
  • Alternative treatments like ezetimibe, bile acid sequestrants, mipomersen, lomitapide, and PCSK9 inhibitors offer options for statin-resistant or intolerant patients.
Keywords:
EzetimibeIntoleranceLDL-cholesterolPCSK9ResistanceStatins

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