The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
Open accessAbstract
BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .).
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“Furthermore, there is no evidence from randomized trials that therapeutically increasing plasma HDL-C reduces the risk of CV events [63-67].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [63]
In the citing paper
“Similarly, in the Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High-Risk for Vascular Outcomes (ACCELERATE) and Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification (REVEAL) trials, treatment with CETP inhibitors more than doubled HDL-C levels, but did not appear to reduce the risk of ASCVD events beyond”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [63]
In the citing paper
“Evacetrapib, which raises HDL-C levels by 130% and lowers LDL-C by 37%, was studied in the ACCELERATE trial [63], which was terminated due to futility.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [63]
In the citing paper
“The CETP inhibitors dalcetrapib (in > 30 000 patients with recent ACS [65]) and evacetrapib (in > 12 000 high-risk patients [63]) were investigated in 2012 and 2017, respectively. Neither clinical study was able to show any clinical benefit associated with CETP inhibitors [65].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [63]
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“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.”
From Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development (2021) · cites this paper as [84]
In the citing paper
“Confounding by linkage disequilibrium can be assessed through colocalization 84”
From Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development (2021) · cites this paper as [84]
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Metadata
- Authors
- The HPS3/TIMI55–REVEAL Collaborative Group
- Affiliations
- University of Oxford (GB)
- Corresponding author
- The HPS3/TIMI55–REVEAL Collaborative Group
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-09-28
- Volume
- 377
- Issue
- 13
- Pages
- 1217-1227
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2762777606
- Cited by
- 1,047
- References
- 28
- Citations by year
- 2026: 72 · 2025: 78 · 2024: 99 · 2023: 92 · 2022: 93 · 2021: 118 · 2020: 107 · 2019: 134 · 2018: 195 · 2017: 54
- FWCI
- 137.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institute for Health and Care Research (NF-SI-0513-10139, NF-SI-0508-10299, RC-PG-0407-10054)
- British Heart Foundation (FS/14/55/30806)
- Versus Arthritis (20639, 18475)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- anacetrapib, cholesteryl ester transfer protein inhibition, atherosclerosis, coronary events, myocardial infarction, coronary revascularization, coronary death, HDL cholesterol, non-HDL cholesterol, LDL cholesterol, atorvastatin, statin therapy, cardiovascular risk reduction, serious adverse events, cancer risk, drug safety, subgroup analysis
- MeSH terms
- Aged, Anticholesteremic Agents, Cholesterol, Coronary Disease, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Incidence, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Oxazolidinones, Atherosclerosis, Kaplan-Meier Estimate, Cholesterol Ester Transfer Proteins, Medication Adherence
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