Drugs Xagena
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.
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 alpha ( TNF-alpha ) 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 cholesterol 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 cholesterol response to statin treatment.
In conclusion, 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. ( Xagena )
Reiner Z, Nutr Metab Cardiovasc Dis 2014;24:1057-1066
XagenaMedicine_2014
