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J Am Coll Cardiol. 2014 Aug 5;64(5):485-94. doi: 10.1016/j.jacc.2014.02.615.

Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials.

Author information

1
Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands.
2
Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
3
Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, Massachusetts.
4
Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France.
5
Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Oslo, Norway.
6
Health Science Center, State University of New York, Brooklyn, New York.
7
Division of Cardiology, San Francisco General Hospital and the University of California at San Francisco, San Francisco, California.
8
Global Pharmaceuticals, Pfizer Inc., New York, New York.
9
NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.
10
The Wesley Hospital, Brisbane, Australia.
11
Centre for Diabetes, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
12
Department of Endocrinology and Diabetes, University College Hospital, London, United Kingdom.
13
Touro University, Mare Island, California.
14
Department of Medicine, University of Texas Health Science Center, San Antonio, Texas; VERDICT, South Texas Veterans Health Care System, San Antonio, Texas.
15
Medical Research Institute, University of Dundee, Dundee, United Kingdom.
16
Weill Cornell Medical College, New York, New York.
17
Center for Human Nutrition, Southwestern Medical Center, University of Texas, Dallas, Texas.
18
Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. Electronic address: j.j.kastelein@amc.uva.nl.

Abstract

BACKGROUND:

Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented.

OBJECTIVES:

The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk.

METHODS:

This meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up.

RESULTS:

Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target <70 mg/dl. Compared with patients who achieved an LDL-C >175 mg/dl, those who reached an LDL-C 75 to <100 mg/dl, 50 to <75 mg/dl, and <50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB.

CONCLUSIONS:

The reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, >40% did not reach an LDL-C target <70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels.

KEYWORDS:

LDL-cholesterol; apolipoprotein B; meta-analysis; non–HDL-cholesterol

PMID:
25082583
PMCID:
PMC4443441
DOI:
10.1016/j.jacc.2014.02.615
[Indexed for MEDLINE]
Free PMC Article

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