The ezetimibe controversy - can this be resolved by comparing the clinical trials with simvastatin and ezetimibe alone and together?

被引:12
作者
Doggrell, Sheila A. [1 ]
机构
[1] Queensland Univ Technol, Sch Biomed Sci, Fac Hlth, Brisbane, Qld 4001, Australia
关键词
cardiovascular disease; clinical outcomes; ezetimibe; LDL-cholesterol; simvastatin; DENSITY-LIPOPROTEIN CHOLESTEROL; LIPID-ALTERING EFFICACY; HUMAN ATHEROSCLEROTIC LESIONS; INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; CARDIOVASCULAR EVENTS; SECONDARY PREVENTION; LDL-CHOLESTEROL; RANDOMIZED-TRIALS; HIGH-RESOLUTION;
D O I
10.1517/14656566.2012.696098
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: The primary target in the treatment of hypercholesterolemia is often to lower low-density lipoprotein (LDL) cholesterol, rather than improve clinical outcomes. Despite the wide use of lipid-modifying drugs, considerable cardiovascular mortality and morbidity remains with this disease. Hypercholesterolemia plays a key role in the development and progression of atherosclerosis and can lead to cardiac heart disease. Areas covered: The purpose of this review is to determine whether ezetimibe has proven clinical benefits; it discusses the clinical trials of simvastatin and ezetimibe alone and in combination. Expert opinion: Simvastatin has been clearly shown to decrease LDL-cholesterol, which is associated with the slowing of atherosclerosis and a reduction in cardiovascular morbidity and mortality. Ezetimibe alone or in the presence of simvastatin lowers LDL-cholesterol. However, ezetimibe alone or in the presence of simvastatin has not been shown to have any irrefutable beneficial effects on atherosclerosis or cardiovascular morbidity and mortality. Thus, until/unless the use of ezetimibe is clearly shown to improve clinical outcomes, its use should be largely restricted to clinical trials investigating clinical outcomes and should not be used routinely in everyday practice.
引用
收藏
页码:1469 / 1480
页数:12
相关论文
共 73 条
[1]   Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12 064 survivors of myocardial infarction: a double-blind randomised trial [J].
Armitage, Jane ;
Bowman, Louise ;
Wallendszus, Karl ;
Bulbulia, Richard ;
Rahimi, Kazem ;
Haynes, Richard ;
Parish, Sarah ;
Peto, Richard ;
Collins, Rory ;
Meade, T. ;
Sleight, P. ;
Collins, R. ;
Armitage, J. ;
Bowman, L. ;
Parish, S. ;
Peto, R. ;
Barton, J. ;
Bray, C. ;
Wincott, E. ;
Dayanandan, R. ;
Clarke, R. ;
Graham, I. ;
Simpson, D. ;
Warlow, C. ;
Wilken, D. ;
Tobert, J. ;
Mushner, T. ;
Doll, R. ;
Wilhelmsen, L. ;
Fox, K. ;
Hill, C. ;
Sandercock, P. ;
Webster, J. ;
Henderson, J. ;
Nixon, A. ;
Lackie, S. ;
Thompson, J. ;
Brown, M. ;
Blackwood, S. ;
Morgan, M. ;
Rhoden, W. ;
Saeed, B. ;
Houghton, M. ;
Nicholson, A. ;
Simpson, C. ;
Hoburn, B. ;
Cooper, I. ;
Gallivan, A. ;
Pickerell, E. ;
Hancock, J. .
LANCET, 2010, 376 (9753) :1658-1669
[2]   Effect of Simvastatin versus placebo on treadmill exercise time until the onset of intermittent claudication in older patients with peripheral arterial disease at six months and at one year after treatment [J].
Aronow, WS ;
Nayak, D ;
Woodworth, S ;
Ahn, C .
AMERICAN JOURNAL OF CARDIOLOGY, 2003, 92 (06) :711-712
[3]  
Avellone G, 2010, INT ANGIOL, V29, P514
[4]   Study of Heart and Renal Protection (SHARP): Randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease [J].
Baigent, C. ;
Landray, M. ;
Reith, C. ;
Dasgupta, T. ;
Emberson, J. ;
Herrington, W. ;
Lewis, D. ;
Mafham, M. ;
Collins, R. ;
Collins, R. ;
Baigent, C. ;
Landray, M. ;
Bray, C. ;
Chen, Y. ;
Baxter, A. ;
Young, A. ;
Hill, M. ;
Knott, C. ;
Cass, A. ;
Feldt-Rasmussen, B. ;
Fellstroem, B. ;
Grobbee, R. ;
Groenhagen-Riska, C. ;
Haas, M. ;
Holdaas, H. ;
Hooi, L. S. ;
Jiang, L. ;
Kasiske, B. ;
Krairittichai, U. ;
Levin, A. ;
Massy, Z. ;
Tesar, V. ;
Walker, R. ;
Wanner, C. ;
Wheeler, D. ;
Wiecek, A. ;
Dasgupta, T. ;
Lewis, D. ;
Mafham, M. ;
Majoni, W. ;
Reith, C. ;
Simpson, D. ;
Strony, J. ;
Musliner, T. ;
Agodoa, L. ;
Armitage, J. ;
Chen, Z. ;
Craig, J. ;
de Zeeuw, D. ;
Gaziano, M. .
AMERICAN HEART JOURNAL, 2010, 160 (05) :785-U28
[5]   Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials [J].
Baigent, C. ;
Blackwell, L. ;
Emberson, J. ;
Holland, L. E. ;
Reith, C. ;
Bhala, N. ;
Peto, R. ;
Barnes, E. H. ;
Keech, A. ;
Simes, J. ;
Collins, R. .
LANCET, 2010, 376 (9753) :1670-1681
[6]   Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins [J].
Baigent, C ;
Keech, A ;
Kearney, PM ;
Blackwell, L ;
Buck, G ;
Pollicino, C ;
Kirby, A ;
Sourjina, T ;
Peto, R ;
Collins, R ;
Simes, J .
LANCET, 2005, 366 (9493) :1267-1278
[7]   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
[8]   Ezetimibe plus simvastatin versus doubling the dose of simvastatin in high cardiovascular risk diabetics: a multicenter, randomized trial (the LEAD study) [J].
Bardini, Gianluca ;
Giorda, Carlo B. ;
Pontiroli, Antonio E. ;
Le Grazie, Cristina ;
Rotella, Carlo M. .
CARDIOVASCULAR DIABETOLOGY, 2010, 9
[9]  
Bays Harold E, 2008, Expert Rev Cardiovasc Ther, V6, P447, DOI 10.1586/14779072.6.4.447
[10]   A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia [J].
Bays, HE ;
Ose, L ;
Fraser, N ;
Tribble, DL ;
Quinto, K ;
Reyes, R ;
Johnson-Levonas, AO ;
Sapre, A ;
Donahue, SR .
CLINICAL THERAPEUTICS, 2004, 26 (11) :1758-1773