BACKGROUND AND AIMS: 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
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