Evacetrapib and cardiovascular outcomes: reasons for lack of efficacy

Filippatos, Theodosios D.; Elisaf, Moses

doi:10.21037/jtd.2017.07.75

Cited by 7 publications

(3 citation statements)

References 25 publications

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“…Low cholesterol levels, on the other hand, have been linked to a higher risk of death in a few studies [6][7][8] . Despite a considerable drop in LDL cholesterol and a concurrent increase in HDLcholesterol, cardiovascular risks in patients remain unchanged in evacetrapib (ACCELERATE) clinical trial results 9 . These contradictory findings show, that dyslipidemias may not be the main source of cardiovascular risk, and that other processes may be at work as well.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Diseases Risk Reduction And Lifestyle Modification:Cross Sectional Ansalysis Of Patient Responses.

2024

JAZ

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A decrease in cardiovascular event risk with a decrease in total and LDL – cholesterol level is termed as “cholesterol paradox” or “risk factor reversal”. Cardiovascular risk does not have a linear relationship between LDL – cholesterol levels, and other substantial risk factors of cardiovascular events are being disregarded.The aim of this study is, to identify modifiable risk factors of cardiovascular events other than those well proved to cause dyslipidemia. A cross-sectional study was conducted with 652 participants in a tertiary care hospital. Patients were grouped into two, based on the history of cardiovascular events. Demographics and patient responses captured using pre-validated questionnaires were analyzed. 5mL blood samples were collected by venipuncture and lipid profile was estimated. Association between cardiovascular events and explanatory variables. was determined using Chi square test and Odds ratio at 95% confidence intervals. Higher risk of CV events was found among smokers 0.232 [0.144 – 0.373]. Consumption of white sugar, refined oil, processed cold beverages and fast food products increased CV risk respectively. Moreover, total cholesterol, LDL-C and triglycerides were found to decrease after one year of counselling the patients. The classical hypothesis of dyslipidemia induced atherosclerosis may not be the predominant cause of CV events. Herein, we report no association between high fat diet and CV risk while we observed higher risk in consumers of refined and ultra processed food products. However, significant control of cholesterol was observed in patients who shifted to Unrefined food products.

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Section: Introductionmentioning

confidence: 99%

Cardiovascular Diseases Risk Reduction And Lifestyle Modification:Cross Sectional Ansalysis Of Patient Responses.

2024

JAZ

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“…Drugs that inhibit CETP are able to increase HDL cholesterol and also to decrease serum LDL cholesterol levels [ 3 ]. However, the randomized placebo-controlled trials that evaluated the effects of three drugs of this class, that is torcetrapib, dalcetrapib and evacetrapib, failed to show a beneficial cardiovascular effect [ 4 , 5 , 6 , 7 ]. These trials were prematurely terminated due to either off-target toxicity (torcetrapib) or lack of efficacy (dalcetrapib, evacetrapib) [ 4 , 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, the randomized placebo-controlled trials that evaluated the effects of three drugs of this class, that is torcetrapib, dalcetrapib and evacetrapib, failed to show a beneficial cardiovascular effect [ 4 , 5 , 6 , 7 ]. These trials were prematurely terminated due to either off-target toxicity (torcetrapib) or lack of efficacy (dalcetrapib, evacetrapib) [ 4 , 5 , 6 , 7 , 8 ]. However, it has been recently reported that in the Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL) trial, anacetrapib, a new CETP inhibitor, led to a significant decrease of cardiovascular events.…”

Section: Introductionmentioning

confidence: 99%

Anacetrapib, a New CETP Inhibitor: The New Tool for the Management of Dyslipidemias?

2017

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Cholesteryl ester transfer protein (CETP) inhibitors significantly increase serum high-density lipoprotein cholesterol (HDL) cholesterol levels and decrease low-density lipoprotein cholesterol (LDL) cholesterol concentration. However, three drugs of this class failed to show a decrease of cardiovascular events in high-risk patients. A new CETP inhibitor, anacetrapib, substantially increases HDL cholesterol and apolipoprotein (Apo) AI levels with a profound increase of large HDL2 particles, but also pre-β HDL particles, decreases LDL cholesterol levels mainly due to increased catabolism of LDL particles through LDL receptors, decreases lipoprotein a (Lp(a)) levels owing to a decreased Apo (a) production and, finally, decreases modestly triglyceride (TRG) levels due to increased lipolysis and increased receptor-mediated catabolism of TRG-rich particles. Interestingly, anacetrapib may be associated with a beneficial effect on carbohydrate homeostasis. Furthermore, the Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL) trial showed that anacetrapib administration on top of statin treatment significantly reduces cardiovascular events in patients with atherosclerotic vascular disease without any significant increase of adverse events despite its long half-life. Thus, anacetrapib could be useful for the effective management of dyslipidemias in high-risk patients that do not attain their LDL cholesterol target or are statin intolerable, while its role in patients with increased Lp(a) levels remains to be established.

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Docking-Based Virtual Screening Using PyRx Tool: Autophagy Target Vps34 as a Case Study

Kondapuram¹,

Sarvagalla²,

Coumar³

2021

Molecular Docking for Computer-Aided Drug Design

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Evacetrapib and cardiovascular outcomes: reasons for lack of efficacy

Cited by 7 publications

References 25 publications

Cardiovascular Diseases Risk Reduction And Lifestyle Modification:Cross Sectional Ansalysis Of Patient Responses.

Cardiovascular Diseases Risk Reduction And Lifestyle Modification:Cross Sectional Ansalysis Of Patient Responses.

Anacetrapib, a New CETP Inhibitor: The New Tool for the Management of Dyslipidemias?

Docking-Based Virtual Screening Using PyRx Tool: Autophagy Target Vps34 as a Case Study

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