keyword
https://read.qxmd.com/read/32941836/cholesteryl-ester-transfer-protein-inhibitors-in-precision-medicine
#1
REVIEW
Xin Su, Guiyang Li, Yingjian Deng, Dong Chang
Dyslipidemia is associated with atherosclerosis and cardiovascular disease development, posing serious risks to human health. Cholesteryl ester transfer protein (CETP) is responsible for exchange of neutral lipids, such as cholesteryl ester and TG, between plasma high density lipoprotein (HDL) particles and Apolipoprotein B-100 (ApoB-100) containing lipoprotein particles. Genetic studies suggest that single-nucleotide polymorphism (SNPs) with loss of activity CETP is associated with increased HDL-C, reduced LDL-C, and cardiovascular risk...
September 14, 2020: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://read.qxmd.com/read/32639518/effect-of-c-reactive-protein-on-lipoprotein-a-associated-cardiovascular-risk-in-optimally-treated-patients-with-high-risk-vascular-disease-a-prespecified-secondary-analysis-of-the-accelerate-trial
#2
Rishi Puri, Steven E Nissen, Benoit J Arsenault, Julie St John, Jeffrey S Riesmeyer, Giacomo Ruotolo, Ellen McErlean, Venu Menon, Leslie Cho, Kathy Wolski, A Michael Lincoff, Stephen J Nicholls
Importance: Although lipoprotein(a) (Lp[a]) is a causal genetic risk factor for atherosclerotic cardiovascular disease, it remains unclear which patients with established atherosclerotic cardiovascular disease stand to benefit the most from Lp(a) lowering. Whether inflammation can modulate Lp(a)-associated cardiovascular (CV) risk during secondary prevention is unknown. Objective: To examine whether Lp(a)-associated CV risk is modulated by systemic inflammation in optimally treated patients at high risk of CV disease...
July 8, 2020: JAMA Cardiology
https://read.qxmd.com/read/32200670/the-mystery-of-evacetrapib-why-are-cetp-inhibitors-failing
#3
EDITORIAL
Stephen J Nicholls, Kristen Bubb
No abstract text is available yet for this article.
March 21, 2020: Expert Review of Cardiovascular Therapy
https://read.qxmd.com/read/32179516/effect-of-cetp-inhibition-with-evacetrapib-in-patients-with-diabetes-mellitus-enrolled-in-the-accelerate-trial
#4
Venu Menon, Anirudh Kumar, Divyang R Patel, Julie St John, Jeffrey Riesmeyer, Govinda Weerakkody, Giacomo Ruotolo, Kathy E Wolski, Ellen McErlean, Paul C Cremer, Stephen J Nicholls, A Michael Lincoff, Steven E Nissen
BACKGROUND: High-density lipoprotein (HDL) levels are inversely associated with cardiovascular risk. Cholesteryl ester transfer protein inhibition with evacetrapib results in a marked increase in HDL and reduction in low-density lipoprotein (LDL) levels. We evaluated the impact of treatment with evacetrapib versus placebo in the subset of 8236 patients with diabetes mellitus (DM) enrolled in the Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes trial...
March 2020: BMJ Open Diabetes Research & Care
https://read.qxmd.com/read/32172237/cholesteryl-ester-transfer-protein-inhibitors-and-cardiovascular-outcomes-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#5
Hossein Taheri, Kristian B Filion, Sarah B Windle, Pauline Reynier, Mark J Eisenberg
BACKGROUND: Cholesteryl ester transfer protein (CETP) inhibitors increase serum high-density lipoprotein cholesterol (HDL-c) concentration; however, their impact on cardiovascular outcomes is not clear. This systematic review examines the effect of CETP inhibitors on serum lipid profiles, cardiovascular events, and all-cause mortality. METHODS: We searched MEDLINE, Embase, and the Cochrane Library of Clinical Trials for placebo-controlled randomized controlled trials (RCTs) that examined the effect of a CETP inhibitor (dalcetrapib, anacetrapib, evacetrapib, or TA-8995) on all-cause mortality, major adverse cardiovascular events (MACE), or the components of MACE at ≥6 months...
March 13, 2020: Cardiology
https://read.qxmd.com/read/31898914/genome-wide-polygenic-score-and-cardiovascular-outcomes-with-evacetrapib-in-patients-with-high-risk-vascular-disease-a-nested-case-control-study
#6
EDITORIAL
Connor A Emdin, Pallav Bhatnagar, Minxian Wang, Sreekumar G Pillai, Lin Li, Hui-Rong Qian, Jeffrey S Riesmeyer, A Michael Lincoff, Stephen J Nicholls, Steven E Nissen, Giacomo Ruotolo, Sekar Kathiresan, Amit V Khera
Genome-wide polygenic scores (GPSs) integrate information from many common DNA variants into a single measure of inherited susceptibility, and can identify individuals who are at substantially elevated risk of developing important common diseases. For coronary artery disease, about 8% of the population can be identified who are at triple the normal risk based on genetic variation alone. Among these high polygenic score individuals, adherence to a healthy lifestyle or use of statins may offset increased inherited risk...
January 3, 2020: Circulation. Genomic and Precision Medicine
https://read.qxmd.com/read/31852422/impact-of-baseline-glycemic-control-on-residual-cardiovascular-risk-in-patients-with-diabetes-mellitus-and-high-risk-vascular-disease-treated-with-statin-therapy
#7
Venu Menon, Anirudh Kumar, Divyang R Patel, Julie St John, Kathy E Wolski, Ellen McErlean, Jeffrey S Riesmeyer, Govinda Weerakkody, Giacomo Ruotolo, Paul C Cremer, Stephen J Nicholls, A Michael Lincoff, Steven E Nissen
Background The contemporary impact of glycemic control on patients with diabetes mellitus at high cardiovascular risk remains unclear. 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...
January 7, 2020: Journal of the American Heart Association
https://read.qxmd.com/read/31752637/plasma-aldosterone-levels-are-not-associated-with-cardiovascular-events-among-patients-with-high-risk-vascular-disease-insights-from-the-accelerate-trial
#8
Anirudh Kumar, Divyang R Patel, Danielle M Brennan, Kathy E Wolski, A Michael Lincoff, Giacomo Ruotolo, Ellen McErlean, Govinda Weerakkody, Jeffrey S Riesmeyer, Stephen J Nicholls, Steven E Nissen, Venu Menon
Background The failure of cholesteryl ester transfer protein inhibitor torcetrapib was associated with an off-target increase in plasma aldosterone. 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...
December 3, 2019: Journal of the American Heart Association
https://read.qxmd.com/read/31054484/evacetrapib-reduces-pre%C3%AE-1-hdl-in-patients-with-atherosclerotic-cardiovascular-disease-or-diabetes
#9
Yunqin Chen, Jibin Dong, Xiaojin Zhang, Xueying Chen, Li Wang, Haozhu Chen, Junbo Ge, Xian-Cheng Jiang
BACKGROUND AND AIMS: Cholesteryl ester transfer protein (CETP) inhibitor-mediated induction of HDL-cholesterol has no effect on the protection from cardiovascular disease (CVD). However, the mechanism is still unknown. Data on the effects of this class of drugs on subclasses of HDL are either limited or insufficient. In this study, we investigated the effect of evacetrapib, a CETP inhibitor, on subclasses of HDL in patients with atherosclerotic cardiovascular disease or diabetes. METHODS: Baseline and 3-month post-treatment samples from atorvastatin 40 mg plus evacetrapib 130 mg (n = 70) and atorvastatin 40 mg plus placebo (n = 30) arms were used for this purpose...
April 14, 2019: Atherosclerosis
https://read.qxmd.com/read/31014095/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
#10
Anirudh Kumar, Divyang R Patel, Kathy E Wolski, A Michael Lincoff, Sangeeta R Kashyap, Giacomo Ruotolo, Ellen McErlean, Govinda Weerakkody, Jeffrey S Riesmeyer, Stephen J Nicholls, Steven E Nissen, Venu Menon
BACKGROUND: Despite optimal treatment, type II diabetes mellitus remains associated with an increased risk for future cardiovascular events. 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...
March 2019: Diabetes & Vascular Disease Research
https://read.qxmd.com/read/30704580/cholesteryl-ester-transfer-protein-inhibition-for-preventing-cardiovascular-events-jacc-review-topic-of-the-week
#11
REVIEW
Jane Armitage, Michael V Holmes, David Preiss
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...
February 5, 2019: Journal of the American College of Cardiology
https://read.qxmd.com/read/30347344/cholesteryl-ester-transfer-protein-an-enigmatic-pharmacology-antagonists-and-agonists
#12
REVIEW
Shizuya Yamashita, Massimiliano Ruscica, Chiara Macchi, Alberto Corsini, Yuji Matsuzawa, Cesare R Sirtori
The cholesteryl ester transfer protein (CETP) system moves cholesteryl esters (CE) from high density lipoproteins (HDL) to lower density lipoproteins, i.e. very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) in exchange for triglycerides (TGs). This shuttle process will ultimately form complexes facilitating a bidirectional exchange of CE and TGs, the end process being CE delivery to catabolic sites. The CETP system is generally characteristic of higher animal species; lower species, not provided with this system, have higher and enlarged HDL enriched with apo E, suitable for tissue receptor interaction...
October 1, 2018: Atherosclerosis
https://read.qxmd.com/read/29630000/what-have-we-learnt-from-the-clinical-outcomes-trials-with-the-cetrapibs
#13
Sheila A Doggrell
PURPOSE OF REVIEW: The current review considers what we have learnt from the clinical outcome trials with the cetrapibs; the inhibitors of cholesteryl ester transfer protein that increase HDL cholesterol levels; torcetrapib, dalcetrapib, evacetrapib and anacetrapib. RECENT FINDINGS: Although an off-target increase in blood pressure may have contributed to the failure of torcetrapib in Investigation of Lipid Level Management to Understand its Impact in Atherosclerotics Events, recent evidence shows that torcetrapib also increased atherogenic apoproteins, and this may have contributed to its failure...
August 2018: Current Opinion in Lipidology
https://read.qxmd.com/read/29525816/adcy9-genetic-variants-and-cardiovascular-outcomes-with-evacetrapib-in-patients-with-high-risk-vascular-disease-a-nested-case-control-study
#14
Steven E Nissen, Sreekumar G Pillai, Stephen J Nicholls, Kathy Wolski, Jeffrey S Riesmeyer, Govinda J Weerakkody, Wendra M Foster, Ellen McErlean, Lin Li, Pallav Bhatnagar, Giacomo Ruotolo, A Michael Lincoff
Importance: A pharmacogenetic analysis of dalcetrapib, a cholesteryl ester transfer protein inhibitor, reported an association between a single-nucleotide polymorphism (SNP) in the ADCY9 gene (rs1967309) and reduction in major adverse cardiovascular events despite a neutral result for the overall trial. Objective: To determine whether the association between the SNP in the ADCY9 gene and a reduction in major adverse cardiovascular events could be replicated for another cholesteryl ester transfer protein inhibitor, evacetrapib, in patients with high-risk vascular disease...
May 1, 2018: JAMA Cardiology
https://read.qxmd.com/read/29498299/cardiovascular-outcomes-trial-with-anacetrapib-in-subjects-with-high-cardiovascular-risk-are-major-benefits-revealed
#15
Sheila A Doggrell
The actions of the cholesteryl ester transfer protein (CETP) inhibitors (torcetrapib, dalcetrapib and evacetrapib) include increasing high-density lipoprotein (HDL) cholesterol, but they do not reduce cardiovascular outcomes in subjects with high cardiovascular risk. Anacetrapib also inhibits CETP, increases HDL cholesterol and lowers low-density lipoprotein (LDL) cholesterol. Areas covered: This evaluation is of the REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid Modification) trial, which was a cardiovascular outcomes trial with anacetrapib in subjects with high cardiovascular risk...
April 2018: Expert Opinion on Pharmacotherapy
https://read.qxmd.com/read/29424255/the-therapeutic-potential-of-cetp-inhibitors-a-patent-review
#16
REVIEW
Xinran Wang, Wei Li, Lijuan Hao, Honglei Xie, Chenzhou Hao, Chunchi Liu, Wenyan Li, Xuqiong Xiong, Dongmei Zhao
Epidemiological studies have identified that high levels of low-density lipoprotein-cholesterol (LDL-C) and low levels of high-density lipoprotein-cholesterol (HDL-C) are two independent causes of cardiovascular disease (CVD). Statins, niacin and fibrate are used for the treatment of CVD. However, some defects are shown in the treatment process. Thus, there is a demand for better treatment strategies that confer preferable efficacy with fewer side effects. Cholesteryl ester transfer protein (CETP) promotes the movement of CEs from HDL to LDL and VLDL in exchange for triglycerides (TGs)...
April 2018: Expert Opinion on Therapeutic Patents
https://read.qxmd.com/read/29287689/present-therapeutic-role-of-cholesteryl-ester-transfer-protein-inhibitors
#17
REVIEW
Nicola Ferri, Alberto Corsini, Cesare R Sirtori, Massimiliano Ruscica
Therapeutic interventions aimed at increasing high-density lipoprotein (HDL) levels in order to reduce the residual cardiovascular (CV) risk of optimally drug treated patients have not provided convincing results, so far. Transfer of cholesterol from extrahepatic tissues to the liver appears to be the major atheroprotective function of HDL, and an elevation of HDL levels could represent an effective strategy. Inhibition of the cholesteryl ester transfer protein (CETP), raising HDL-cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, reduces low-density lipoprotein-cholesterol (LDL-C) and apoB levels, thus offering a promising approach...
February 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/28932532/evacetrapib-and-cardiovascular-outcomes-reasons-for-lack-of-efficacy
#18
EDITORIAL
Theodosios D Filippatos, Moses S Elisaf
No abstract text is available yet for this article.
August 2017: Journal of Thoracic Disease
https://read.qxmd.com/read/28839974/effect-of-evacetrapib-on-cardiovascular-outcomes-in-patients-with-high-risk-cardiovascular-disease
#19
EDITORIAL
Wilbert S Aronow
No abstract text is available yet for this article.
July 2017: Journal of Thoracic Disease
https://read.qxmd.com/read/28799819/no-cardiovascular-benefit-with-evacetrapib-is-this-the-end-of-the-road-for-the-cetrapibs
#20
Sheila A Doggrell
Increasing high-density lipoprotein(HDL) cholesterol levels predict improved cardiovascular outcomes. However, inhibiting cholesteryl ester transfer protein (CETP) to increase HDL cholesterol, with the 'cetrapibs' (torcetrapib and dalcetrapib), did not improve cardiovascular clinical outcomes. Despite these findings, the clinical outcomes trial with evacetrapib continued. Areas covered: Treatment with evacetrapib increased the levels of HDL by ~130%, and decreased low-density lipoprotein (LDL) cholesterol by ~37%...
October 2017: Expert Opinion on Pharmacotherapy
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