Z Reiner1. 1. 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.
Abstract
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 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.
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 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: Arrigo F G Cicero; Alessandro Colletti; Gani Bajraktari; Olivier Descamps; Dragan M Djuric; Marat Ezhov; Zlatko Fras; Niki Katsiki; Michel Langlois; Gustavs Latkovskis; Demosthenes B Panagiotakos; Gyorgy Paragh; Dimitri P Mikhailidis; Olena Mitchenko; Bernhard Paulweber; Daniel Pella; Christos Pitsavos; Željko Reiner; Kausik K Ray; Manfredi Rizzo; Amirhossein Sahebkar; Maria-Corina Serban; Laurence S Sperling; Peter P Toth; Dragos Vinereanu; Michal Vrablík; Nathan D Wong; Maciej Banach Journal: Arch Med Sci Date: 2017-08-04 Impact factor: 3.318