evacetrapib (LY2484595) / Eli Lilly 
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  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    Preclinical, Journal:  CETP inhibitor evacetrapib enters mouse brain tissue. (Pubmed Central) -  Aug 3, 2023   
    Besides its robust effects on LDL and HDL cholesterol, it has an acceptable safety profile. We show that evacetrapib crosses the blood-brain barrier and is detectable in brain tissue 0.5
  • ||||||||||  Review, Journal:  Structure-based mechanism and inhibition of cholesteryl ester transfer protein. (Pubmed Central) -  Mar 24, 2023   
    Insights into the structural-based CETP-lipoprotein interactions can unravel CETP inhibition machinery, which can hopefully guide the design of more effective CETP inhibitors that combat ASCVD. Individual-molecule 3D structures of CETP bound to lipoproteins provide a model for understanding the mechanism by which CETP mediates lipid transfer and which in turn, guide the rational design of new anti-ASCVD therapeutics.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    CETP INHIBITOR EVACETRAPIB SHOWS BENEFICIAL EFFECTS IN AN AD MOUSE MODEL (On-Demand Oral Gallery B) -  Dec 23, 2022 - Abstract #ADPD2023ADPD_201;    
    Interestingly, evacetrapib rescued cognition in hAPP/hCETPtg mice. Good cognition correlated positively with higher HDL and lower LDL levels, but APP and A
  • ||||||||||  Journal:  CETP-inhibitors: from HDL-C to LDL-C lowering agents? (Pubmed Central) -  Nov 15, 2022   
    Although first-generation CETP inhibitors (torcetrapib, dalcetrapib) were mainly raising HDL-C or had off-target effects, next generation CETP inhibitors (anacetrapib, evacetrapib) were also effective in reducing LDL-C and apoB and have been proven safe...The newest-generation CETP inhibitor obicetrapib, specifically designed to lower LDL-C and apoB, has achieved significant reductions of LDL-C up to 45%. Obicetrapib, about to enter phase III development, could become the first CETP inhibitor as add-on therapy for patients not reaching their guideline LDL-C targets.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    Journal:  Longitudinal High-Sensitivity C-Reactive Protein and Longer-Term Cardiovascular Outcomes in Optimally-Treated Patients With High-Risk Vascular Disease. (Pubmed Central) -  Aug 18, 2022   
    We performed a post hoc analysis of ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibitor with Evacetrapib in Patients with High-Risk for Vascular Outcomes), involving optimally-treated patients with high-risk vascular disease, with available baseline and at least 1 follow-up hsCRP level...In the setting of established medical therapies, longitudinal follow-up hsCRP was independently associated with long-term MACE. In conclusion, these findings suggest that longitudinal hsCRP represents a novel approach of residual cardiovascular risk even when on-treatment hsCRP levels remain <2 mg/L.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly, Tasigna (nilotinib) / Novartis, Inhibikase, ABT-737 / AbbVie
    Journal:  High-affinity SOAT1 ligands remodeled cholesterol metabolism program to inhibit tumor growth. (Pubmed Central) -  Aug 10, 2022   
    In conclusion, these findings suggest that longitudinal hsCRP represents a novel approach of residual cardiovascular risk even when on-treatment hsCRP levels remain <2 mg/L. Taken together, we reported several high-affinity SOAT1 ligands and demonstrated their clinical potential in the precision therapy of liver cancer, and also reveal the potential antitumor mechanism of SOAT1-targeting compounds.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    Journal:  Cholesterol metabolism in Alzheimer's disease. (Pubmed Central) -  Feb 4, 2022   
    CETP may play an aggravating role in AD, which has not yet been investigated since mice naturally lack CETP. We propose that CETP inhibitors such as evacetrapib may be promising pharmacological treatments contributing to the prevention of cognitive decline in AD.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    [VIRTUAL] Cholesterol Metabolism in Alzheimer’s Disease () -  Aug 2, 2021 - Abstract #AAIC2021AAIC_2294;    
    CETP may play an aggravating role in AD, which has not yet been investigated since mice naturally lack CETP. We propose that CETP inhibitors such as evacetrapib may be promising pharmacological treatments contributing to the prevention of cognitive decline in AD.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly, dalcetrapib (JTT-705) / DalCor, anacetrapib (MK-0859) / Merck (MSD)
    Review, Journal:  Cholesteryl ester transfer protein inhibitors in precision medicine. (Pubmed Central) -  Jun 22, 2021   
    Although REVEAL trail has recently shown that Anacetrapib could reduce major coronary events, it was also shown to induce excessive lipid accumulation in adipose tissue; thereby, the further regulatory approval will not be sought...In the present review, we summarize the current understanding of the functions of CETP and the outcomes of the phase III randomized controlled trials of CETP inhibitors. In addition, we also put forward the implications from results of the trials which potentially suggest that the CETP inhibitors could be a promising precise therapeutic medicine for CVD based on genetic background.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    Clinical, Journal:  Plasma Aldosterone Levels Are Not Associated With Cardiovascular Events Among Patients With High-Risk Vascular Disease: Insights From the ACCELERATE Trial. (Pubmed Central) -  Jan 9, 2021   
    P3
    We sought to evaluate the impact of evacetrapib on plasma aldosterone level and determine the association between plasma aldosterone level and major adverse cardiovascular events among patients with stable high-risk vascular disease enrolled in the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial...Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01687998.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    Clinical, Journal:  Impact of Baseline Glycemic Control on Residual Cardiovascular Risk in Patients With Diabetes Mellitus and High-Risk Vascular Disease Treated With Statin Therapy. (Pubmed Central) -  Dec 23, 2020   
    P3
    We evaluated the utility of hemoglobin A1c (HbA1c) as a marker of risk on the composite end point of cardiovascular death, nonfatal myocardial infarction, stroke, hospitalization for unstable angina, and coronary revascularization in an optimally treated population with diabetes mellitus and established coronary artery disease enrolled in the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial...Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01687998.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly, dalcetrapib (JTT-705) / Roche, Japan Tobacco, anacetrapib (MK-0859) / Merck (MSD)
    Review, Journal:  Cholesteryl ester transfer protein: An enigmatic pharmacology - Antagonists and agonists. (Pubmed Central) -  Nov 23, 2019   
    The pharmacological approach to the CETP system remains enigmatic, although the failure of CETP antagonists has dampened enthusiasm. Studies on the system, a crossroad for any investigation on cholesterol metabolism, have however provided crucial contributions and will still be confronting any scientist working on CV prevention.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly, dalcetrapib (JTT-705) / Roche, Japan Tobacco, anacetrapib (MK-0859) / Merck (MSD)
    Review, Journal:  Cholesteryl Ester Transfer Protein Inhibition for Preventing Cardiovascular Events: JACC Review Topic of the Week. (Pubmed Central) -  Nov 23, 2019   
    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.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    Clinical, Journal:  ADCY9 Genetic Variants and Cardiovascular Outcomes With Evacetrapib in Patients With High-Risk Vascular Disease: A Nested Case-Control Study. (Pubmed Central) -  Sep 28, 2019   
    When adjusted for cardiovascular risk factors, the OR for evacetrapib was 0.93 (95% CI, 0.73-1.19) for the AA genotype, 1.05 (95% CI, 0.91-1.22) for the AG genotype, and 1.02 (95% CI 0.85-1.24) for the GG genotype; interaction P = .71 and trend P = .59. Pharmacogenetic analysis did not show a significant association between the ADCY9 SNP (rs1967309) and cardiovascular benefit or harm for the cholesteryl ester transfer protein inhibitor evacetrapib.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly, dalcetrapib (JTT-705) / Roche, Japan Tobacco, anacetrapib (MK-0859) / Merck (MSD)
    Clinical, Clinical data, Journal:  What have we learnt from the clinical outcomes trials with the cetrapibs? (Pubmed Central) -  Sep 28, 2019   
    Pharmacogenetic analysis did not show a significant association between the ADCY9 SNP (rs1967309) and cardiovascular benefit or harm for the cholesteryl ester transfer protein inhibitor evacetrapib. Collectively, these clinical outcome trials do not support raising HDL cholesterol by inhibiting cholesteryl ester transfer protein, as a mechanism for improving cardiovascular outcomes, in the total population of subjects with coronary artery disease.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    Clinical, Journal, Adverse events:  Baseline fasting plasma insulin levels predict risk for major adverse cardiovascular events among patients with diabetes and high-risk vascular disease: Insights from the ACCELERATE trial. (Pubmed Central) -  Aug 15, 2019   
    We sought to determine the association between baseline fasting plasma insulin levels and major adverse cardiovascular outcomes in patients with type II diabetes mellitus and high-risk vascular disease enrolled in the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial...In a contemporary population of patients with type II diabetes mellitus and high-risk vascular disease on optimum medical therapy, baseline hyperinsulinaemia was an independent predictor for major adverse cardiovascular outcomes and need of future coronary revascularization. These results suggest a pathophysiological link between hyperinsulinaemia and progression of atherosclerotic vascular disease among diabetics.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly, dalcetrapib (JTT-705) / Roche, Japan Tobacco, anacetrapib (MK-0859) / Merck (MSD)
    Journal:  The Trials and Tribulations of CETP Inhibitors. (Pubmed Central) -  Jun 22, 2019   
    Anacetrapib treatment was associated with a small increase in BP, but was devoid of major side effects and was also associated with a small reduction in diabetes. Treatment with CETP inhibitors, either alone or in combination with statins, could provide another option for patients with coronary disease who require further reduction in LDL and/or non-HDL cholesterol.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    Enrollment change:  A Study of LY2484595 on Pharmacokinetics in Healthy Participants (clinicaltrials.gov) -  Apr 20, 2019   
    P1,  N=82, Completed, 
    Treatment with CETP inhibitors, either alone or in combination with statins, could provide another option for patients with coronary disease who require further reduction in LDL and/or non-HDL cholesterol. N=60 --> 82
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    Biomarker, Journal:  Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease. (Pubmed Central) -  May 24, 2017   
    P3
    Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .).
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    Trial termination:  ACCELERATE: A Study of Evacetrapib in High-Risk Vascular Disease (clinicaltrials.gov) -  Dec 13, 2016   
    P3,  N=12092, Terminated, 
    (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .). Completed --> Terminated; Study termination due to insufficient efficacy.
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    Trial completion:  ACCELERATE: A Study of Evacetrapib in High-Risk Vascular Disease (clinicaltrials.gov) -  Aug 16, 2016   
    P3,  N=12116, Completed, 
    Completed --> Terminated; Study termination due to insufficient efficacy. Active, not recruiting --> Completed
  • ||||||||||  evacetrapib (LY2484595) / Eli Lilly
    Trial completion:  A Study of Evacetrapib in Participants With Abnormal Cholesterol (clinicaltrials.gov) -  Jan 26, 2016   
    P1,  N=101, Completed, 
    Active, not recruiting --> Completed | N=147 --> 68 Active, not recruiting --> Completed