Differences in Action of Atorvastatin and Ezetimibe in Lowering Low-Density Lipoprotein Cholesterol and Effect on Endothelial Function

Matsue, Yuya; Matsumura, Akihiko; Hashimoto, Yuji; Yoshida, Masayuki

doi:10.1253/circj.cj-13-0033

Cited by 24 publications

(15 citation statements)

References 44 publications

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“…62 Several studies randomized healthy volunteers or patients with CHD to protocols comparing high dose statins to a combination of lower dose statins and ezetimibe and reported greater improvement in endothelial function and vascular inflammation with high dose statins, despite comparable lowering of LDL-C in both groups. 63-66 Other studies did not find differences between groups, suggesting the absence of statin pleiotropy. 67-69 Additional evidence for pleiotropy stems from studies that report effects of statins that were observed before serum LDL-C was lowered.…”

Section: Introductionmentioning

confidence: 95%

Pleiotropic Effects of Statins on the Cardiovascular System

Oesterle

Laufs

Liao

2017

Circulation Research

952

684

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The 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors (statins), have been used for thirty years to prevent coronary artery disease and stroke. Their primary mechanism of action is the lowering of serum cholesterol through inhibiting hepatic cholesterol biosynthesis thereby upregulating the hepatic low-density lipoprotein (LDL) receptors and increasing the clearance of LDL-cholesterol (LDL-C). Statins may exert cardiovascular protective effects that are independent of LDL-C lowering called “pleiotropic” effects. Because statins inhibit the production of isoprenoid intermediates in the cholesterol biosynthetic pathway, the post-translational prenylation of small guanosine triphosphate binding proteins such as Rho and Rac, and their downstream effectors such as Rho kinase and nicotinamide adenine dinucleotide phosphate oxidases are also inhibited. In cell culture and animal studies, these effects alter the expression of endothelial nitric oxide synthase, the stability of atherosclerotic plaques, the production of pro-inflammatory cytokines and reactive oxygen species, the reactivity of platelets, and the development of cardiac hypertrophy and fibrosis. The relative contributions of statin pleiotropy to clinical outcomes, however, remain a matter of debate and are hard to quantify since the degree of isoprenoid inhibition by statins correlates to some extent with the amount of LDL-C reduction. This review examines some of the currently proposed molecular mechanisms for statin pleiotropy and discusses whether they could have any clinical relevance in cardiovascular disease.

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Section: Introductionmentioning

confidence: 95%

Pleiotropic Effects of Statins on the Cardiovascular System

Oesterle

Laufs

Liao

2017

Circulation Research

952

684

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“…Most of the LDL‐C–lowering effect of statins occurs at the starting dose, and doubling the dose of statin results in only 6% further reduction in LDL‐C level . Sometimes a reincrease in LDL level occurs after the initial decrease.…”

Section: Discussionmentioning

confidence: 99%

Effect of Combination Therapy of Ezetimibe and Atorvastatin on Remnant Lipoprotein Versus Double Atorvastatin Dose in Egyptian Diabetic Patients

El-Tamalawy

Ibrahim

Hassan

et al. 2017

The Journal of Clinical Pharma

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A high level of remnant lipoprotein cholesterol (RLP-C) is a predominant feature in diabetic patients with atherosclerosis.This study aimed to investigate the effect of ezetimibe added to statin therapy compared to doubling standard statin dose. Sixty-five eligible patients were recruited then prospectively randomized to receive ezetimibe 10 mg/day plus their 40 mg daily atorvastatin dose (group 1) or atorvastatin 80 mg/day (group 2) for 3 months. Efficacy was evaluated using plasma levels of RLP-C, apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL), percentage of brachial artery flow-mediated dilation, and lipid profile. Forty patients completed the study and provided efficacy data. Group 1 showed more reduction in RLP-C (45.7% vs 31.7%, P = .02), apolipoprotein B (28.5% vs 9.5%, P = .01), total cholesterol (34.7% vs 24.6%, P = .003), triglycerides (49% vs 24.4%, P = .000), non-HDL (49.3% vs 33%, P = .002), and low-density lipoprotein cholesterol (49.6% vs 35.2%, P = .02) compared to group 2. Group 1 showed a greater increase in HDL (66% vs 35%, P = .002); and flow-mediated dilation (30% vs 17%, P = .01) compared to group 2. It is concluded that adding ezetimibe 10 mg to atorvastatin 40 mg may be a better choice than doubling atorvastatin dose in improving RLPs, endothelial function, and lipid profile in diabetic cardiovascular patients who could not achieve their therapeutic treatment goals with the standard atorvastatin dose.

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“…According to the previous reports [26,27], we hypothesize in this study that LDL-C levels should be decreased by approximately 30 mg/dL in the combination therapy group versus the monotherapy group (1.75-fold higher lowering rate), when LDL-C levels at the start of treatment are 140 mg/dL. In order to determine the sample size of this study, we also referred to two previous studies on change in YGP by statin.…”

Section: Sample Sizementioning

confidence: 96%