New therapeutic principles in dyslipidaemia: focus on LDL and Lp(a) lowering drugs

被引:87
作者
Norata, Giuseppe Danilo [1 ,2 ,3 ]
Ballantyne, Christie M. [4 ,5 ]
Catapano, Alberico Luigi [1 ,6 ]
机构
[1] Univ Milan, Dept Pharmacol & Biomol Sci, I-20133 Milan, Italy
[2] Osped Bassini, Soc Italiana Studio Aterosclerosi, Ctr Study Atherosclerosis, Cinisello Balsamo, Italy
[3] Queen Mary Univ, Barts & London Sch Med & Dent, Blizard Inst, Ctr Diabet, London, England
[4] Baylor Coll Med, Dept Med, Houston, TX 77030 USA
[5] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA
[6] IRCCS Multimed, Milan, Italy
关键词
Dyslipidaemia; Pharmacology; PCSK9; Apolipoprotein B; SUBTILISIN/KEXIN TYPE 9; DENSITY-LIPOPROTEIN CHOLESTEROL; TRIGLYCERIDE TRANSFER PROTEIN; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; B SYNTHESIS INHIBITOR; MONOCLONAL-ANTIBODY; DOUBLE-BLIND; HIGH-RISK; ANTISENSE OLIGONUCLEOTIDE; COMBINATION THERAPY;
D O I
10.1093/eurheartj/eht088
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Dyslipidaemias play a key role in determining cardiovascular risk; the discovery of statins has contributed a very effective approach. However, many patients do not achieve, at the maximal tolerated dose, the recommended goals for low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol, and apolipoprotein B (apoB). Available agents combined with statins can provide additional LDL-C reduction, and agents in development will increase therapeutic options impacting also other atherogenic lipoprotein classes. In fact, genetic insights into mechanisms underlying regulation of LDL-C levels has expanded potential targets of drug therapy and led to the development of novel agents. Among them are modulators of apoB containing lipoproteins production and proprotein convertase subtilisin/kexin type-9 inhibitors. Alternative targets such as lipoprotein(a) also require attention; however, until we have a better understanding of these issues, further LDL-C lowering in high and very high-risk patients will represent the most sound clinical approach.
引用
收藏
页码:1783 / +
页数:8
相关论文
共 52 条
[1]   Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia [J].
Akdim, Fatima ;
Tribble, Diane L. ;
Flaim, JoAnn D. ;
Yu, Rosie ;
Su, John ;
Geary, Richard S. ;
Baker, Brenda F. ;
Fuhr, Rainard ;
Wedel, Mark K. ;
Kastelein, John J. P. .
EUROPEAN HEART JOURNAL, 2011, 32 (21) :2650-2659
[2]   Effect of Mipomersen, an Apolipoprotein B Synthesis Inhibitor, on Low-Density Lipoprotein Cholesterol in Patients With Familial Hypercholesterolemia [J].
Akdim, Fatima ;
Visser, Maartje E. ;
Tribble, Diane L. ;
Baker, Brenda F. ;
Stroes, Erik S. G. ;
Yu, Rosie ;
Flaim, Joann D. ;
Su, John ;
Stein, Evan A. ;
Kastelein, John J. P. .
AMERICAN JOURNAL OF CARDIOLOGY, 2010, 105 (10) :1413-1419
[3]   The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial [J].
Baigent, Colin ;
Landray, Martin J. ;
Reith, Christina ;
Emberson, Jonathan ;
Wheeler, David C. ;
Tomson, Charles ;
Wanner, Christoph ;
Krane, Vera ;
Cass, Alan ;
Craig, Jonathan ;
Neal, Bruce ;
Jiang, Lixin ;
Hooi, Lai Seong ;
Levin, Adeera ;
Agodoa, Lawrence ;
Gaziano, Mike ;
Kasiske, Bertram ;
Walker, Robert ;
Massy, Ziad A. ;
Feldt-Rasmussen, Bo ;
Krairittichai, Udom ;
Ophascharoensuk, Vuddidhej ;
Fellstrom, Bengt ;
Holdaas, Hallvard ;
Tesar, Vladimir ;
Wiecek, Andrzej ;
Grobbee, Diederick ;
de Zeeuw, Dick ;
Gronhagen-Riska, Carola ;
Dasgupta, Tanaji ;
Lewis, David ;
Herrington, William ;
Mafham, Marion ;
Majoni, William ;
Wallendszus, Karl ;
Grimm, Richard ;
Pedersen, Terje ;
Tobert, Jonathan ;
Armitage, Jane ;
Baxter, Alex ;
Bray, Christopher ;
Chen, Yiping ;
Chen, Zhengming ;
Hill, Michael ;
Knott, Carol ;
Parish, Sarah ;
Simpson, David ;
Sleight, Peter ;
Young, Alan ;
Collins, Rory .
LANCET, 2011, 377 (9784) :2181-2192
[4]   ETC-1002 LOWERS LDL-C AND BENEFICIALLY MODULATES OTHER CARDIO-METABOLIC RISK FACTORS IN HYPERCHOLESTEROLEMIC SUBJECTS WITH EITHER NORMAL OR ELEVATED TRIGLYCERIDES [J].
Ballantyne, Christie M. ;
Davidson, Michael ;
MacDougall, Diane ;
Margulies, Janice ;
DiCarlo, Lorenzo ;
Newton, Roger .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2012, 59 (13) :E1625-E1625
[5]   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
[6]   Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy [J].
Boden, William E. ;
Probstfield, Jeffrey L. ;
Anderson, Todd ;
Chaitman, Bernard R. ;
Desvignes-Nickens, Patrice ;
Koprowicz, Kent ;
McBride, Ruth ;
Teo, Koon ;
Weintraub, William .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (24) :2255-2267
[7]   Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk [J].
Calandra, Sebastiano ;
Tarugi, Patrizia ;
Speedy, Helen E. ;
Dean, Andrew F. ;
Bertolini, Stefano ;
Shoulders, Carol C. .
JOURNAL OF LIPID RESEARCH, 2011, 52 (11) :1885-1926
[8]   Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): Comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes [J].
Cannon, Christopher P. ;
Giugliano, Robert P. ;
Blazing, Michael A. ;
Harrington, Robert A. ;
Peterson, John L. ;
Sisk, Christine McCrary ;
Strony, John ;
Musliner, Thomas A. ;
McCabe, Carolyn H. ;
Veltri, Enrico ;
Braunwald, Eugene ;
Califf, Robert M. .
AMERICAN HEART JOURNAL, 2008, 156 (05) :826-832
[9]   Safety of Anacetrapib in Patients with or at High Risk for Coronary Heart Disease. [J].
Cannon, Christopher P. ;
Shah, Sukrut ;
Dansky, Hayes M. ;
Davidson, Michael ;
Brinton, Eliot A. ;
Gotto, Antonio M., Jr. ;
Stepanavage, Michael ;
Liu, Sherry Xueyu ;
Gibbons, Patrice ;
Ashraf, Tanya B. ;
Zafarino, Jennifer ;
Mitchel, Yale ;
Barter, Philip .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (25) :2406-2415
[10]   The new joint EAS/ESC guidelines for the management of dyslipidaemias [J].
Catapano, Alberico L. ;
Chapman, John ;
Wiklund, Olov ;
Taskinen, Marji-Riitta .
ATHEROSCLEROSIS, 2011, 217 (01) :1-1