STATE-OF-THE-ART PAPERS
Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds
A meta-analysis of randomized controlled trials
Rakesh S. Birjmohun, MD*,*,
Barbara A. Hutten, PhD ,
John J.P. Kastelein, MD, PhD* and
Erik S.G. Stroes, MD, PhD*
* Department of Vascular Medicine
Department of Clinical Epidemiology and Biostatistics, Academic Medical Center of Amsterdam, Amsterdam, the Netherlands
Manuscript received May 10, 2004;
accepted October 4, 2004.
* Reprint requests and correspondence: Dr. Rakesh S. Birjmohun, Academic Medical Center of Amsterdam, Department of Vascular Medicine, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands (Email: r.s.birjmohun{at}amc.uva.nl).
OBJECTIVES: The aim of this research was to estimate the efficacy and safety of current high-density lipoprotein cholesterol (HDL-C)-increasing drugs.
BACKGROUND: Epidemiologic evidence has shown that HDL-C is inversely related to coronary heart disease (CHD) risk. However, the evidence for reducing CHD risk by raising HDL-C is thin, predominantly due to the paucity of effective and safe HDL-increasing drugs.
METHODS: Randomized controlled trials with fibrates and niacin, published between 1966 through February 2004 (MEDLINE), were retrieved. Information on treatment, baseline characteristics, serum lipids, end points, and side-effects were independently abstracted by two authors using a standardized protocol.
RESULTS: Data from 53 trials (16,802 subjects) using fibrates and 30 trials (4,749 subjects) using niacin were included. Random-effects model showed 11% versus 10% reduction in total cholesterol, 36% versus 20% reduction in triglycerides, 8% versus 14% reduction in low-density lipoprotein cholesterol, and 10% versus 16% increase in HDL-C for fibrates and niacin, respectively. Apart from flushes in the niacin group, both fibrates and niacin were shown to be well-tolerated and safe. Fibrates reduced the risk for major coronary events by 25% (95% confidence interval 10% to 38%), whereas current available data for niacin indicate a 27% reduction.
CONCLUSIONS: Fibrates reduce major coronary events and increase HDL-C levels without significant toxicity. Niacin has a more potent effect on HDL-C levels, whereas data on cardiovascular event rate reduction are limited. Future studies need to evaluate whether additional HDL increase by fibrates or particularly newer niacin formulations on top of statin therapy translates into further event reduction in high-risk subjects, without significant toxicity.
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Abbreviations and Acronyms
| | CHD = coronary heart disease | | CV = cardiovascular | | ER = extended-release | | HDL-C = high-density lipoprotein cholesterol | | HHS = Helsinki Heart study | | IR = immediate-release | | LDL-C = low-density lipoprotein cholesterol | | SD = standard deviation | | SR = wax-matrix sustained-release | | TC = total cholesterol | | TG = triglycerides | | VA-HIT = Veterans Affairs High-density lipoprotein Intervention Trial |
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ehp399v1.
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29(9):
1336 - 1341.
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|
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|
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|
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Eur. Heart J.,
August 1, 2009;
30(15):
1894 - 1902.
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|
|
|
|
|
|
|
W. A Ghali and N. Rodondi
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BMJ,
February 16, 2009;
338(feb16_1):
a3065 - a3065.
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|
|
|
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Arterioscler Thromb Vasc Biol,
November 1, 2008;
28(11):
2016 - 2022.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. J. Hime, A. S. Black, J. J. Bulgrien, and L. K. Curtiss
Leukocyte-derived hepatic lipase increases HDL and decreases en face aortic atherosclerosis in LDLr-/- mice expressing CETP
J. Lipid Res.,
October 1, 2008;
49(10):
2113 - 2123.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. B. Goldberg and T. A. Jacobson
Effects of Niacin on Glucose Control in Patients With Dyslipidemia
Mayo Clin. Proc.,
April 1, 2008;
83(4):
470 - 478.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. A. van der Steeg, I. Holme, S. M. Boekholdt, M. L. Larsen, C. Lindahl, E. S.G. Stroes, M. J. Tikkanen, N. J. Wareham, O. Faergeman, A. G. Olsson, et al.
High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies.
J. Am. Coll. Cardiol.,
February 12, 2008;
51(6):
634 - 642.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Steiner
Atherosclerosis in type 2 diabetes: a role for fibrate therapy?
Diabetes and Vascular Disease Research,
December 1, 2007;
4(4):
368 - 374.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. D. Brunzell
Hypertriglyceridemia
N. Engl. J. Med.,
September 6, 2007;
357(10):
1009 - 1017.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ardoin, C. Sandborg, and L. Schanberg
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Lupus,
August 1, 2007;
16(8):
618 - 626.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. C. van der Hoogt, W. de Haan, M. Westerterp, M. Hoekstra, G. M. Dallinga-Thie, J. A. Romijn, H. M. G. Princen, J. W. Jukema, L. M. Havekes, and P. C. N. Rensen
Fenofibrate increases HDL-cholesterol by reducing cholesteryl ester transfer protein expression
J. Lipid Res.,
August 1, 2007;
48(8):
1763 - 1771.
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[Full Text]
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|
|
|
|
|
|
|
E. Windler, M. Schoffauer, and B.-C. Zyriax
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Diabetes and Vascular Disease Research,
June 1, 2007;
4(2):
136 - 142.
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|
|
|
|
|
|
|
S. Kodama, S. Tanaka, K. Saito, M. Shu, Y. Sone, F. Onitake, E. Suzuki, H. Shimano, S. Yamamoto, K. Kondo, et al.
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Arch Intern Med,
May 28, 2007;
167(10):
999 - 1008.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
W S A Smellie, J Forth, S R S Smart, M J Galloway, W Irving, D Bareford, P O Collinson, K G Kerr, G Summerfield, P J Carey, et al.
Best practice in primary care pathology: review 7
J. Clin. Pathol.,
May 1, 2007;
60(5):
458 - 465.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Reasner
Rational therapy of mixed dyslipidaemia in a patient with diabetes
The British Journal of Diabetes & Vascular Disease,
January 1, 2007;
7(1):
25 - 30.
[Abstract]
[PDF]
|
|
|
|
|
|
|
P. K. Shah
Inhibition of CETP as a novel therapeutic strategy for reducing the risk of atherosclerotic disease
Eur. Heart J.,
January 1, 2007;
28(1):
5 - 12.
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|
|
|
|
|
|
|
A. S Wierzbicki
Fibrates after the FIELD study: some answers, more questions
Diabetes and Vascular Disease Research,
December 1, 2006;
3(3):
166 - 171.
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|
|
|
|
|
|
|
A. Kontush and M. J. Chapman
Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis
Pharmacol. Rev.,
September 1, 2006;
58(3):
342 - 374.
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|
|
|
|
|
|
|
M J. Chapman
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September 1, 2006;
3(1_suppl):
S6 - S9.
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|
|
|
|
|
|
|
T. R Pedersen, G. Assmann, J.-P. Bassand, M J. Chapman, R. Erbel, and C. Sirtori
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September 1, 2006;
3(2_suppl):
S1 - S12.
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|
|
|
|
|
|
|
A. Steinmetz
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Diabetes and Vascular Disease Research,
September 1, 2006;
3(1_suppl):
S10 - S15.
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|
|
|
|
|
|
|
C. D. Rochester and C. E. Cooke
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Journal of Pharmacy Practice,
April 1, 2006;
19(2):
79 - 93.
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|
|
|
|
|
|
|
P. C.N. Rensen and L. M. Havekes
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Arterioscler Thromb Vasc Biol,
April 1, 2006;
26(4):
681 - 684.
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|
|
|
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|
|
|
K. Ullman
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February 1, 2006;
3(2):
9 - 9.
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|
|
|
|
|
|
|
M J. Chapman
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The British Journal of Diabetes & Vascular Disease,
January 1, 2006;
6(1):
11 - 19.
[Abstract]
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|
|
|
|
|
|
|
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JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice
Heart,
December 1, 2005;
91(suppl_5):
v1 - v52.
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|
|
|
|
|
|
|
E. Bruckert
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Eur. Heart J. Suppl.,
November 1, 2005;
7(suppl_L):
L16 - L20.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
A. M. Gotto Jr
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J. Am. Coll. Cardiol.,
October 4, 2005;
46(7):
1219 - 1224.
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
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