Statin and ezetimibe combination therapy in cardiovascular disease

Dembowski, Ewa; Davidson, Michael

doi:10.1097/med.0b013e3283295297

Cited by 22 publications

(24 citation statements)

References 46 publications

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“…Traditionally, ezetimibe is administered to patients already receiving statin therapy. 28 The finding that the combined treatment started simultaneously was well tolerated indicates that the administration of both a statin and ezetimibe may be initiated at the same time.…”

Section: Discussionmentioning

confidence: 99%

“…First, the study was short in duration, did not assess clinical outcomes, and the study population, although exceeding the required sample size, was relatively low. Second, the doses of both simvastatin and ezetimibe, although commonly used in the clinical practice, 28 are not the maximal, ones and therefore, it remains unanswered whether the effects of these agents on cytokine release and plasma hsCRP is stronger when they are given at highest doses. We cannot exclude the fact that for ezetimibe a reduction in cytokine release may reach the level of significance, provided more patients are enrolled in the study.…”

Section: Discussionmentioning

confidence: 99%

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The Effect of Ezetimibe and Simvastatin on Monocyte Cytokine Release in Patients With Isolated Hypercholesterolemia

Krysiak

2011

Journal of Cardiovascular Pharmacology

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Apart from reducing plasma lipids, ezetimibe may produce non-lipid-related pleiotropic effects. The aim of this article was to compare the effect of ezetimibe and simvastatin on monocyte cytokine release and systemic inflammation in isolated hypercholesterolemic patients. One hundred thirty-four subjects with isolated hypercholesterolemia were allocated to 1 of 4 treatment groups treated for 90 days with, respectively, ezetimibe, simvastatin, ezetimibe plus simvastatin, or placebo. Monocyte cytokine release was determined at baseline and after 30 and 90 days of treatment. Compared with placebo, all the remaining treatment options reduced-monocyte release of tumor necrosis factor-α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1, which was accompanied by a reduction in plasma C-reactive protein levels. In subjects receiving both simvastatin and ezetimibe, posttreatment monocyte cytokine release and plasma C-reactive protein levels did not differ from those observed in 30 matched healthy subjects. Monocyte-suppressing and systemic-anti-inflammatory effects were more expressed in simvastatin- than in ezetimibe-treated patients and strongest when both the agents were administered together. The results obtained suggest that simvastatin may be a better treatment option than ezetimibe in isolated hypercholesterolemic patients and that hypercholesterolemic patients of high cardiovascular risk may benefit the most from combined treatment with simvastatin and ezetimibe.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Effect of Ezetimibe and Simvastatin on Monocyte Cytokine Release in Patients With Isolated Hypercholesterolemia

Krysiak

2011

Journal of Cardiovascular Pharmacology

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“…Foley et al [7] demonstrated that 52% of high-risk hyperlipidemic patients did not achieve the LDL-C goal with an initial dose of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), and that 86% of these patients had still not reached the goal after 6 months. Dembowski et al showed that only 18% of these patients achieved the LDL-C treatment goal with statin monotherapy [8]. One reason is that the initiation dose of statins is most effective and doubling the dose achieves only a 6% additional reduction in LDL-C levels [9].…”

Section: European and Other Societies On Cardiovascular Disease Prevementioning

confidence: 99%

Ezetimibe and Vascular Endothelial Function

Ikeda¹,

Maemura

2011

CVP

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Hypercholesterolemia is a major risk factor for cardiovascular diseases that has been managed mostly with 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors (statins) that suppress de novo cholesterol synthesis in the liver. Statins also have beneficial pleiotropic effects on the atherosclerotic process that are independent of their ability to lower lipid values. However, the levels of low-density lipoprotein cholesterol (LDL-C) in most hypercholesterolemic patients at high risk for cardiovascular disease do not reach the goals proposed by guidelines even when prescribed with statins. Ezetimibe is a new lipid-lowering agent that blocks the intestinal absorption of dietary and biliary cholesterol and reduces LDL-C levels, especially when combined with statins. However, its effect on cardiovascular events remains unknown. We reviewed the effects of ezetimibe on cardiovascular diseases, in particular, vascular endothelial function, which is initially impaired during the atherogenetic process and an important predictor of cardiovascular events. Increasing evidence suggests that ezetimibe improves endothelial function and nitric oxide availability, and reduces inflammation as well as oxidative stress. However, this mechanism has not been clarified and limited, large trials and cohort studies have not shown that this agent prevents cardiovascular events. Ezetimibe has just recently become commercially available, which might explain the paucity of evidence regarding its benefits and effects on cardiovascular morbidity and mortality.

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“…5 As monotherapy, ezetimibe at 10 mg reduces LDL-C by approximately 17%, but when added to any dose of statin, it reduces LDL-C by an additional 25%. 6 Given the well-established log-linear relationship between LDL-C and relative risk for CHD, these greater degrees of LDL-C reduction can be expected to result in improved clinical outcomes, although this has not yet been proven in the case of ezetimibe. 1,6 Existing data have not established a lower threshold beyond which LDL-C reduction ceases to be beneficial.…”

Section: Article See P 28mentioning

confidence: 99%

“…6 Given the well-established log-linear relationship between LDL-C and relative risk for CHD, these greater degrees of LDL-C reduction can be expected to result in improved clinical outcomes, although this has not yet been proven in the case of ezetimibe. 1,6 Existing data have not established a lower threshold beyond which LDL-C reduction ceases to be beneficial. In secondary prevention, the Treating to New Targets (TNT) study in patients with CHD demonstrated that intensive statin therapy to a mean LDL-C of 77 mg/dL, as compared with a mean LDL-C of 101 mg/dL in the standard treatment group, confers a 22% relative reduction in the risk of a first major cardiovascular event, with no clinically significant increase in adverse event rates.…”

Section: Article See P 28mentioning

confidence: 99%

Improving Lipid Goal Attainment

Gotto

2009

Circulation

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Statin and ezetimibe combination therapy in cardiovascular disease

Cited by 22 publications

References 46 publications

The Effect of Ezetimibe and Simvastatin on Monocyte Cytokine Release in Patients With Isolated Hypercholesterolemia

The Effect of Ezetimibe and Simvastatin on Monocyte Cytokine Release in Patients With Isolated Hypercholesterolemia

Ezetimibe and Vascular Endothelial Function

Improving Lipid Goal Attainment

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