Cholesteryl Ester Transfer Protein Inhibition for Preventing Cardiovascular Events
Open accessAbstract
Cholesteryl ester transfer protein (CETP) facilitates exchange of triglycerides and cholesteryl ester between high-density lipoprotein (HDL) and apolipoprotein B100-containing lipoproteins. Evidence from genetic studies that variants in the CETP gene were associated with higher blood HDL cholesterol, lower low-density lipoprotein cholesterol, and lower risk of coronary heart disease suggested that pharmacological inhibition of CETP may be beneficial. To date, 4 CETP inhibitors have entered phase 3 cardiovascular outcome trials. Torcetrapib was withdrawn due to unanticipated off-target effects that increased risk of death, and major trials of dalcetrapib and evacetrapib were terminated early for futility. In the 30,000-patient REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid Modification) trial, anacetrapib doubled HDL cholesterol, reduced non-HDL cholesterol by 17 mg/dl (0.44 mmol/l), and reduced major vascular events by 9% over 4 years, but anaceptrapib was found to accumulate in adipose tissue, and regulatory approval is not being sought. Therefore, despite considerable initial promise, CETP inhibition provides insufficient cardiovascular benefit for routine use.
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Colocalization can be used to test for such bias, but can suffer from issues of lack of power and/or availability of suitable data from relevant tissues.
“Colocalization, which is a statistical approach that quantifies the extent to which two traits share the same underlying causal variant, and thus can be used to infer vertical pleiotropy 83-85 , can be used to test for such bias 86 , but can suffer from issues of lack of power and/or availability of suitable data from relevant tissues.”
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- Authors
- Armitage, J., Holmes, M. V., & Preiss, D.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Armitage, Jane
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 73
- Issue
- 4
- Pages
- 477-487
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC6354546
- OpenAlex
- W2911625798
- Cited by
- 140
- References
- 46
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 19 · 2023: 11 · 2022: 15 · 2021: 30 · 2020: 28 · 2019: 17 · 2018: 1
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research
- British Heart Foundation (18/23/33512, RE/13/1/30181, FS/18/23/33512)
- University of Oxford (RE/13/1/30181)
- Merck Sharp and Dohme
- Medical Research Council (13/1/30181, RE/13/1/30181)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- cholesteryl ester transfer protein, CETP inhibitors, cardiovascular events, HDL cholesterol, anacetrapib, torcetrapib, dalcetrapib, evacetrapib, coronary artery disease, non-HDL cholesterol, cardiovascular outcome trials, drug safety, adipose tissue accumulation
- MeSH terms
- Animals, Anticholesteremic Agents, Cardiovascular Diseases, Humans, Cholesterol, LDL, Clinical Trials, Phase III as Topic, Cholesterol Ester Transfer Proteins
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