Effects of an Inhibitor of Cholesteryl Ester Transfer Protein on HDL Cholesterol
Open accessAbstract
BACKGROUND: Decreased high-density lipoprotein (HDL) cholesterol levels constitute a major risk factor for coronary heart disease; however, there are no therapies that substantially raise HDL cholesterol levels. Inhibition of cholesteryl ester transfer protein (CETP) has been proposed as a strategy to raise HDL cholesterol levels. METHODS: We conducted a single-blind, placebo-controlled study to examine the effects of torcetrapib, a potent inhibitor of CETP, on plasma lipoprotein levels in 19 subjects with low levels of HDL cholesterol (<40 mg per deciliter [1.0 mmol per liter]), 9 of whom were also treated with 20 mg of atorvastatin daily. All the subjects received placebo for four weeks and then received 120 mg of torcetrapib daily for the following four weeks. Six of the subjects who did not receive atorvastatin also participated in a third phase, in which they received 120 mg of torcetrapib twice daily for four weeks. RESULTS: Treatment with 120 mg of torcetrapib daily increased plasma concentrations of HDL cholesterol by 61 percent (P<0.001) and 46 percent (P=0.001) in the atorvastatin and non-atorvastatin cohorts, respectively, and treatment with 120 mg twice daily increased HDL cholesterol by 106 percent (P<0.001). Torcetrapib also reduced low-density lipoprotein (LDL) cholesterol levels by 17 percent in the atorvastatin cohort (P=0.02). Finally, torcetrapib significantly altered the distribution of cholesterol among HDL and LDL subclasses, resulting in increases in the mean particle size of HDL and LDL in each cohort. CONCLUSIONS: In subjects with low HDL cholesterol levels, CETP inhibition with torcetrapib markedly increased HDL cholesterol levels and also decreased LDL cholesterol levels, both when administered as monotherapy and when administered in combination with a statin.
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Drug-based inhibition of CETP in humans leads to a significant increase in HDL-C and a drop in LDL-C.
“Drug-based inhibition of CETP in humans leads to a significant increase in HDL-C and a drop in LDL-C [104, 105].”
From HDL cholesterol: reappraisal of its clinical relevance (2017) · cites this paper as [104]
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- Authors
- Brousseau, M. E., Schaefer, E. J., Wolfe, M. L., Bloedon, L. T., Digenio, A. G., Clark, R. W., Mancuso, J. P., & Rader, D. J.
- Affiliations
- Tufts University (US)
- University of Pennsylvania (US)
- Pfizer (United States) (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2004-04-08
- Volume
- 350
- Issue
- 15
- Pages
- 1505-1515
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2131620609
- Cited by
- 774
- References
- 44
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 9 · 2023: 10 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 14 · 2018: 10 · 2017: 16 · 2016: 14 · 2015: 19 · 2014: 33 · 2013: 30 · 2012: 30
- FWCI
- 105.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL060935)
- National Center for Research Resources (M01RR000054, M01RR000040)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- torcetrapib, cholesteryl ester transfer protein inhibition, HDL cholesterol, low HDL cholesterol, LDL cholesterol, atorvastatin, statin combination therapy, lipoprotein subclasses, particle size, coronary heart disease risk, lipid-lowering therapy
- MeSH terms
- Atorvastatin, Adult, Aged, Anticholesteremic Agents, Carrier Proteins, Drug Therapy, Combination, Female, Glycoproteins, Heptanoic Acids, Humans, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Pyrroles, Quinolines, Triglycerides, Single-Blind Method, Apolipoprotein A-I, Apolipoprotein A-II, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cholesterol Ester Transfer Proteins
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