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.
|
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 |
|
This article has been cited by other articles:

|
 |

|
 |
 
M. J. Chapman, W. Le Goff, M. Guerin, and A. Kontush
Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors
Eur. Heart J.,
October 12, 2009;
(2009)
ehp399v1.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Franssen, R. R. Sankatsing, E. Hassink, B. Hutten, M. T. Ackermans, K. Brinkman, R. Oesterholt, A. Arenas-Pinto, S. P. Storfer, J. J. Kastelein, et al.
Nevirapine Increases High-Density Lipoprotein Cholesterol Concentration by Stimulation of Apolipoprotein A-I Production
Arterioscler Thromb Vasc Biol,
September 1, 2009;
29(9):
1336 - 1341.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. J.E. Sattler, J. Herrmann, S. Yun, N. Lehmann, Z. Wang, G. Heusch, S. Sack, R. Erbel, and B. Levkau
High high-density lipoprotein-cholesterol reduces risk and extent of percutaneous coronary intervention-related myocardial infarction and improves long-term outcome in patients undergoing elective percutaneous coronary intervention
Eur. Heart J.,
August 1, 2009;
30(15):
1894 - 1902.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. A Ghali and N. Rodondi
HDL cholesterol and cardiovascular risk
BMJ,
February 16, 2009;
338(feb16_1):
a3065 - a3065.
[Full Text]
|
 |
|

|
 |

|
 |
 
J. W.A. van der Hoorn, W. de Haan, J. F.P. Berbee, L. M. Havekes, J. W. Jukema, P. C.N. Rensen, and H. M.G. Princen
Niacin Increases HDL by Reducing Hepatic Expression and Plasma Levels of Cholesteryl Ester Transfer Protein in APOE*3Leiden.CETP Mice
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
Review: Management of dyslipidemia in children and adolescents with systemic lupus erythematosus
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.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Windler, M. Schoffauer, and B.-C. Zyriax
The significance of low HDL-cholesterol levels in an ageing society at increased risk for cardiovascular disease
Diabetes and Vascular Disease Research,
June 1, 2007;
4(2):
136 - 142.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Kodama, S. Tanaka, K. Saito, M. Shu, Y. Sone, F. Onitake, E. Suzuki, H. Shimano, S. Yamamoto, K. Kondo, et al.
Effect of Aerobic Exercise Training on Serum Levels of High-Density Lipoprotein Cholesterol: A Meta-analysis
Arch Intern Med,
May 28, 2007;
167(10):
999 - 1008.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. S Wierzbicki
Fibrates after the FIELD study: some answers, more questions
Diabetes and Vascular Disease Research,
December 1, 2006;
3(3):
166 - 171.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
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.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M J. Chapman
The effects of fibrates on lipid metabolism and inflammation in type 2 diabetes
Diabetes and Vascular Disease Research,
September 1, 2006;
3(1_suppl):
S6 - S9.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
T. R Pedersen, G. Assmann, J.-P. Bassand, M J. Chapman, R. Erbel, and C. Sirtori
Reducing residual cardiovascular risk: the relevance of raising high-density lipoprotein cholesterol in patients on cholesterol-lowering treatment
Diabetes and Vascular Disease Research,
September 1, 2006;
3(2_suppl):
S1 - S12.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Steinmetz
Lipid-lowering therapy in type 2 diabetes: a review of the evidence
Diabetes and Vascular Disease Research,
September 1, 2006;
3(1_suppl):
S10 - S15.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
C. D. Rochester and C. E. Cooke
The Changing Face of Dyslipidemia Therapies
Journal of Pharmacy Practice,
April 1, 2006;
19(2):
79 - 93.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
P. C.N. Rensen and L. M. Havekes
Cholesteryl Ester Transfer Protein Inhibition: Effect on Reverse Cholesterol Transport?
Arterioscler Thromb Vasc Biol,
April 1, 2006;
26(4):
681 - 684.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Ullman
HDL Becoming Important Piece of CHD Puzzle
DOC News,
February 1, 2006;
3(2):
9 - 9.
[Full Text]
|
 |
|

|
 |

|
 |
 
M J. Chapman
Review: Fibrates: therapeutic review
The British Journal of Diabetes & Vascular Disease,
January 1, 2006;
6(1):
11 - 19.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
Prepared by: British Cardiac Society, British Hype
JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice
Heart,
December 1, 2005;
91(suppl_5):
v1 - v52.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Bruckert
Impact of lipid treatment on cardiovascular risk reduction: new therapeutic targets
Eur. Heart J. Suppl.,
November 1, 2005;
7(suppl_L):
L16 - L20.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Gotto Jr
Evolving Concepts of Dyslipidemia, Atherosclerosis, and Cardiovascular Disease: The Louis F. Bishop Lecture
J. Am. Coll. Cardiol.,
October 4, 2005;
46(7):
1219 - 1224.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Other articles noted
Evid. Based Med.,
August 1, 2005;
10(4):
127 - 128.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Barter
Role of nicotinic acid in raising high-density lipoprotein cholesterol (HDL-C) to reduce cardiovascular risk: an Asian/Pacific consensus: The Pan-Asian Consensus Panel On Hdl-C
The British Journal of Diabetes & Vascular Disease,
March 1, 2005;
5(2_suppl):
S1 - S15.
[Abstract]
[PDF]
|
 |
|
|