Looking into the Crystal Ball-Upcoming Drugs for Dyslipidemia

被引:8
作者
George, Melvin [1 ]
Selvarajan, Sandhiya [2 ]
Muthukumar, Rajaram [1 ]
Elangovan, Shanmugam [1 ]
机构
[1] SRM Med Coll Hosp & Res Ctr, Dept Cardiol, Madras 603203, Tamil Nadu, India
[2] Jawaharlal Inst Postgrad Med Educ & Res, Dept Clin Pharmacol, Pondicherry, India
关键词
dyslipidemia; hypercholesterolemia; drugs; novel; CETP inhibitors; PCSK9; inhibitors; ESTER TRANSFER PROTEIN; TRIGLYCERIDE TRANSFER PROTEIN; SUBTILISIN/KEXIN TYPE 9; DENSITY-LIPOPROTEIN CHOLESTEROL; APOLIPOPROTEIN-C-III; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; FARNESOID-X-RECEPTOR; MONOCLONAL-ANTIBODY; CARDIOVASCULAR RISK; INHIBITOR ANACETRAPIB;
D O I
10.1177/1074248414545127
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Dyslipidaemia is a critical risk factor for the development of cardiovascular complications such as ischemic heart disease and stroke. Although statins are effective anti-dyslipidemic drugs, their usage is fraught with issues such as failure of adequate lipid control in 30% of cases and intolerance in select patients. The limited potential of other alternatives such as fibrates, bile acid sequestrants and niacin has spurred the search for novel drug molecules with better efficacy and safety. CETP inhibitors such as evacetrapib and anacetrapib have shown promise in raising HDL besides LDL lowering property. Microsomal triglyceride transfer protein (MTP) inhibitors such as lomitapide and Apo CIII inhibitors such as mipomersen have recently been approved in Familial Hypercholesterolemia but experience in the non-familial setting is pretty much limited. One of the novel anti-dyslipidemic drugs which is greatly anticipated to make a mark in LDL-C control is the PCSK9 inhibitors. Some of the anti-dyslipidemic drugs which work by PCSK9 inhibition include evolocumab, alirocumab and ALN-PCS. Other approaches that are being given due consideration include farnesoid X receptor modulation and Lp-PLA2 inhibition. While it may not be an easy proposition to dismantle statins from their current position as a cholesterol reducing agent and as a drug to reduce coronary and cerebro-vascular atherosclerosis, our improved understanding of the disease and appropriate harnessing of resources using sound and robust technology could make rapid in-roads in our pursuit of the ideal anti-dyslipidemic drug.
引用
收藏
页码:11 / 20
页数:10
相关论文
共 81 条
[1]   Effects of torcetrapib in patients at high risk for coronary events [J].
Barter, Philip J. ;
Caulfield, Mark ;
Eriksson, Mats ;
Grundy, Scott M. ;
Kastelein, John J. P. ;
Komajda, Michel ;
Lopez-Sendon, Jose ;
Mosca, Lori ;
Tardif, Jean-Claude ;
Waters, David D. ;
Shear, Charles L. ;
Revkin, James H. ;
Buhr, Kevin A. ;
Fisher, Marian R. ;
Tall, Alan R. ;
Brewer, Bryan .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (21) :2109-2122
[2]   Cholesteryl ester transfer protein - A novel target for raising HDL and inhibiting atherosclerosis [J].
Barter, PJ ;
Brewer, HB ;
Chapman, MJ ;
Hennekens, CH ;
Rader, DJ ;
Tall, AR .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2003, 23 (02) :160-167
[3]  
Bochem AE, 2013, CURR PHARM DESIGN, V19, P3143
[4]   HDL-c is a powerful lipid predictor of cardiovascular diseases [J].
Bruckert, E. ;
Hansel, B. .
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, 2007, 61 (11) :1905-1913
[5]   MTP inhibition as a treatment for dyslipidaemias: time to deliver or empty promises? [J].
Burnett, John R. ;
Watts, Gerald F. .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2007, 11 (02) :181-189
[6]   Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure [J].
Cao, Guoqing ;
Beyer, Thomas P. ;
Zhang, Youyan ;
Schmidt, Robert J. ;
Chen, Yan Q. ;
Cockerham, Sandra L. ;
Zimmerman, Karen M. ;
Karathanasis, Sotirios K. ;
Cannady, Ellen A. ;
Fields, Todd ;
Mantlo, Nathan B. .
JOURNAL OF LIPID RESEARCH, 2011, 52 (12) :2169-2176
[7]   Anacetrapib promotes reverse cholesterol transport and bulk cholesterol excretion in Syrian golden hamsters [J].
Castro-Perez, Jose ;
Briand, Francois ;
Gagen, Karen ;
Wang, Sheng-Ping ;
Chen, Ying ;
McLaren, David G. ;
Shah, Vinit ;
Vreeken, Rob J. ;
Hankemeier, Thomas ;
Sulpice, Thierry ;
Roddy, Thomas P. ;
Hubbard, Brian K. ;
Johns, Douglas G. .
JOURNAL OF LIPID RESEARCH, 2011, 52 (11) :1965-1973
[8]   An ABC of apolipoprotein C-III: a clinically useful new cardiovascular risk factor? [J].
Chan, D. C. ;
Chen, M. M. ;
Ooi, E. M. M. ;
Watts, G. F. .
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, 2008, 62 (05) :799-809
[9]   The Farnesoid X receptor - A molecular link between bile acid and lipid and glucose metabolism [J].
Claudel, T ;
Staels, B ;
Kuipers, F .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2005, 25 (10) :2020-2031
[10]   Clinical pharmacological properties of mipomersen (Kynamro), a second generation antisense inhibitor of apolipoprotein B [J].
Crooke, Stanley T. ;
Geary, Richard S. .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2013, 76 (02) :269-276