title: Resistance and intolerance to statins.
abstract: OBJECTIVE
  Many patients treated with statins are considered statin-resistant because they fail to achieve adequate reduction of low density lipoprotein cholesterol (LDL-C) levels. Some patients are statin-intolerant because they are unable to tolerate statin therapy at all or to tolerate a full therapeutic statin dose because of adverse effects, particularly myopathy and increased activity of liver enzymes.
  
  
  RESULTS
  The resistance to statins has been associated with polymorphisms in the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-R), P-glycoprotein (Pg-P/ABCB1), breast cancer resistance protein (BCRP/ABCG2), multidrug resistance-associated proteins (MRP1/ABCC1 and MRP2/ABCC2), organic anion transporting polypeptides (OATP), RHOA, Nieman-Pick C1-like1 protein (NPC1L1), farnesoid X receptor (FXR), cholesterol 7alpha-hydroxylase (CYP7A1), Apolipoprotein E (ApoE), proprotein convertase subtilisin/kexin type 9 (PCSK9), low density lipoprotein receptor (LDLR), lipoprotein (a) (LPA), cholesteryl ester transfer protein (CETP), and tumor necrosis factor α (TNF-α) genes. However, currently, there is still not enough evidence to advocate pharmacogenetic testing before initiating statin therapy. Patients with inflammatory states and HIV infection also have diminished LDL-C lowering as a response to statin treatment. Pseudo-resistance due to nonadherence or non-persistence in real-life circumstances is probably the main cause of insufficient LDL-C response to statin treatment.
  
  
  CONCLUSIONS
  If a patient is really statin-resistant or statin-intolerant, several other treatment possibilities are nowadays available: ezetimibe alone or in combination with bile acid sequestrants, and possibly in the near future mipomersen, lomitapide, or monoclonal antibodies against PCSK9.
authors.affiliation: Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia. Electronic address: zreiner@kbc-zagreb.hr.
authors.forename: Z
authors.initials: Z
authors.lastname: Reiner
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001384:Azetidines / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000097:blood; D004351:Drug Resistance / Q000235:genetics*; D004359:Drug Therapy, Combination; D004361:Drug Tolerance / Q000235:genetics*; D000069438:Ezetimibe; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy; D000089762:Multidrug Resistance-Associated Protein 2; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
chemical_list: C000715087:ABCC2 protein, human; D000924:Anticholesteremic Agents; D001384:Azetidines; C473731:BMS201038; D001562:Benzimidazoles; D001647:Bile Acids and Salts; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000089762:Multidrug Resistance-Associated Protein 2; D000069438:Ezetimibe
keywords: Ezetimibe; Intolerance; LDL-cholesterol; PCSK9; Resistance; Statins