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Evacetrapib reduces pre?-1 HDL in patients with atherosclerotic cardiovascular disease or diabetes.

ABSTRACT: 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. Four subclasses of HDL (large HDL, medium HDL, small HDL, and pre?-1 HDL) were separated according to their size and quantified by densitometry using a recently developed native polyacrylamide gel electrophoresis (PAGE) system. RESULTS:Relative to placebo, while evacetrapib treatment dramatically increased large HDL and medium HDL subclasses, it significantly reduced small HDL (27%) as well as pre?-1 HDL (36%) particles. Evacetrapib treatment reduced total LDL, but also resulted in polydisperse LDL with LDL particles larger and smaller than the LDL subclasses of the placebo group. CONCLUSION:Evacetrapib reduced pre?-1 HDL and small HDL in patients with ASCVD or diabetes on statin. Pre?-1 HDL and medium HDL are negatively interrelated. The results could give a clue to understand the effect of CETP inhibitors on cardiovascular outcomes.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6548311 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Evacetrapib reduces preβ-1 HDL in patients with atherosclerotic cardiovascular disease or diabetes.

Chen Yunqin Y Dong Jibin J Zhang Xiaojin X Chen Xueying X Wang Li L Chen Haozhu H Ge Junbo J Jiang Xian-Cheng XC

Atherosclerosis 20190414

<h4>Background and aims</h4>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.<h4>Metho ...[more]

PMID: 31054484

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Project description:AimsThe total cholesterol (TC)/high-density lipoprotein (HDL) cholesterol ratio may carry additional information not available in more commonly used single cholesterol measures. Analysis of discordance between lipid parameters might help assess the impact of such additional information on the risk of atherosclerotic cardiovascular disease. We aimed to investigate the role of the TC/HDL-cholesterol ratio in determining atherosclerotic cardiovascular disease risk when discordant with low-density lipoprotein (LDL) cholesterol and non-HDL-cholesterol.MethodsWe studied 14,403 Atherosclerosis Risk in Communities (ARIC) study participants who were free of atherosclerotic cardiovascular disease at baseline. TC/HDL-cholesterol discordance with LDL-cholesterol (estimated by the novel Martin/Hopkins method) and non-HDL-cholesterol was assessed at five visits and determined by being at or above the median for each lipid parameter. We constructed Cox proportional hazard models to estimate the risk for incident atherosclerotic cardiovascular disease events associated with each lipid concordance/discordance category using a time-varying approach.ResultsMean age of participants was 54.1 years, 56% women and 25% black. There were 2634 atherosclerotic cardiovascular disease events over a median (interquartile range) follow-up of 24.2 (16.0-25.4) years. Among individuals with LDL-cholesterol and non-HDL-cholesterol less than the median, 26% and 21% had discordant TC/HDL-cholesterol at or above the median, respectively. These individuals had a 24% (hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.09, 1.41) and 29% (HR 1.29, 95% CI 1.13, 1.46) greater risk of incident atherosclerotic cardiovascular disease, respectively, compared to those with TC/HDL-cholesterol less than the median after multivariable adjustment. In individuals with diabetes with LDL-cholesterol or non-HDL-cholesterol less than the median, discordant TC/HDL-cholesterol at or above the median was more prevalent at 48% and 38%, respectively.ConclusionClinically significant discordance exists between TC/HDL-cholesterol, available from the standard lipid profile, and the routinely used non-HDL-cholesterol and LDL-cholesterol. Such discordance may help inform atherosclerotic cardiovascular disease risk management, particularly in individuals with diabetes in whom discordance is more common.

Project description:Background 2018 American Heart Association/American College of Cardiology cholesterol guideline recommends statin in patients with chronic and/or stable liver disease for secondary prevention of atherosclerotic cardiovascular disease yet remains equivocal on the adequate intensity of statin for patients with chronic liver disease (CLD). We aimed to assess the association between statin intensity and mortality among patients with CLD with atherosclerotic cardiovascular disease. Methods and Results We conducted a population-based cohort study in South Korea. We assessed the risk of survival and clinical outcomes using inverse probability of treatment-weighted Cox proportional hazards regression. We also estimated the absolute risk difference between treatment groups based on the Poisson distribution. During an average of 2.35 person-years, 10 442 patients with CLD with atherosclerotic cardiovascular disease were identified. Among those patients, 5515 (52.8%) received high-intensity statin, and 4927 (47.2%) received low/moderate-intensity statin. High-intensity statin was associated with lower risk for all-cause mortality (hazard ratio [HR], 0.83 [95% CI, 0.75-0.92]), cardiovascular-cause mortality (HR, 0.85 [0.71-1.01]), liver-cause mortality (HR, 0.72 [0.54-0.97]) compared with low/moderate-intensity statin. Although both hospitalizations for recurrent myocardial infarction and stroke were shown to be increased among high-intensity statin users, effect estimate was homogeneous in the absolute scale (myocardial infarction: HR, 1.12 [1.04-1.19], risk difference, 7.57 [-0.69 to 15.84] per 1000 person-years; stroke: HR, 1.11 [0.97 to 1.27]; risk difference, -1.70 [-5.19 to 1.78]). Conclusions Among patients with CLD with atherosclerotic cardiovascular disease, high-intensity statin was significantly associated with a lower risk of mortality. These findings herein support the guidelines for statin use in patients with CLD while demonstrating potential benefit of optimal intensity use.

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Evacetrapib reduces pre?-1 HDL in patients with atherosclerotic cardiovascular disease or diabetes.

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Evacetrapib reduces preβ-1 HDL in patients with atherosclerotic cardiovascular disease or diabetes.

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