Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin

Pesaro, Antônio Eduardo Pereira; Serrano, Carlos; Fernandes, Juliano Lara; Cavalcanti, Alexandre Biasi; Campos, Alexandre; Martins, Herlon Saraiva; Maranhão, Raul C.; Lemos, James A. de; Souza, Heraldo Possolo de; Nicolau, José Carlos

doi:10.1016/j.ijcard.2011.01.062

Cited by 44 publications

(21 citation statements)

References 31 publications

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“…Our results were similar to those of a meta-analysis in the VOYAGER study, which showed that rosuvastatin (10 mg/day) increases HDL-C by 6.1 ± 0.5% from baseline [38]. In contrast, others have found that adding ezetimibe does not significantly increase HDL-C from baseline [25,39,40]. Therefore, these results suggest that increasing the dose of statin elevates HDL-C more effectively than adding ezetimibe.…”

Section: Discussionsupporting

confidence: 88%

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Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe

et al. 2013

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BackgroundStatins are frequently administered to reduce low-density lipoprotein cholesterol (LDL-C) and vascular inflammation, because LDL-C and high sensitive C-reactive protein (hs-CRP) are associated with high risk for cardiovascular events. When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery disease (CAD), ezetimibe can be added or the statin dose can be increased. However, which strategy is more effective for treating patients with CAD has not been established. The present study compares anti-inflammatory effects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose or by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients.Methods46 patients with high-risk CAD and LDL-C and hs-CRP levels of >70 mg/dL and >1.0 mg/L, respectively, that were not improved by 4 weeks of rosuvastatin (2.5 mg/day) were randomly assigned to receive 10 mg (R10, n = 24) of rosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe (R2.5/E10, n = 22) for 12 weeks. The primary endpoint was a change in hs-CRP.ResultsBaseline characteristics did not significantly differ between the groups. At 12 weeks, LDL-C and inflammatory markers (hs-CRP, interleukin-6, tumour necrosis factor-alpha and pentraxin 3) also did not significantly differ between the two groups (LDL-C: R10 vs. R2.5/E10: -19.4 ± 14.2 vs. -22.4 ± 14.3 mg/dL). However, high-density lipoprotein cholesterol (HDL-C) was significantly improved in the R10, compared with R2.5/E10 group (4.6 ± 5.9 vs. 0.0 ± 6.7 mg/dL; p < 0.05).ConclusionBoth enhanced therapies exerted similar anti-inflammatory effects under an equal LDL-C reduction in patients with high-risk CAD despite 2.5 mg/day of rosuvastatin. However, R10 elevated HDL-C more effectively than R2.5/E10.Trial registrationUMIN000003746

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Section: Discussionsupporting

confidence: 88%

“…A simvastatin study with a similar protocol to the present study found no significant improvements in hs-CRP and IL-6 [25]. Likewise, changes in inflammatory markers did not significantly differ between R10 and the R2.5/E10 in the present study, in which the protocol was designed so that both strategies would similarly reduce LDL-C.…”

Section: Discussionsupporting

confidence: 48%

Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe

et al. 2013

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“…Ezetimibe/Simvastatin and Rosuvastatin have been shown to reduce LPO after 16 weeks of treatment in type 2 DM patients with DPN, although no clinical outcomes were drastically changed compared to placebo [135]. However, a study performed in coronary artery disease patients where Ezetimibe/Simvastatin 10/20 mg was compared to Simvastatin 80 mg as monotherapy demonstrated that inflammation biomarkers (CRP, IL-6, monocyte chemoattractant protein-1, and soluble CD40) were unaltered after 6 weeks of treatment, probably explained by the theory that the target of statins resides on oxidative stress rather than inflammatory response [136]. A study performed in healthy male subjects treated with Simvastatin monotherapy showed no changes in oxidative stress to nucleic acids, LPO, and plasma antioxidants [137], probably due to the lack of free radicals increase, since Ezetimibe alone has been shown to reduce 8-isoprostanes and reactive oxygen metabolites levels only in hypercholesterolemic patients with high oxidative stress at baseline, but not in those with near-normal oxidative status [138].…”

Section: Diabetic Polyneuropathymentioning

confidence: 99%

Diabetic Polyneuropathy in Type 2 Diabetes Mellitus: Inflammation, Oxidative Stress, and Mitochondrial Function

Román-Pintos

Villegas-Rivera

Rodríguez-Carrizález

et al. 2016

Journal of Diabetes Research

181

152

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Diabetic polyneuropathy (DPN) is defined as peripheral nerve dysfunction. There are three main alterations involved in the pathologic changes of DPN: inflammation, oxidative stress, and mitochondrial dysfunction. Inflammation induces activation of nuclear factor kappa B, activator protein 1, and mitogen-activated protein kinases. Oxidative stress induced by hyperglycemia is mediated by several identified pathways: polyol, hexosamine, protein kinase C, advanced glycosylation end-products, and glycolysis. In addition, mitochondrial dysfunction accounts for most of the production of reactive oxygen and nitrosative species. These free radicals cause lipid peroxidation, protein modification, and nucleic acid damage, to finally induce axonal degeneration and segmental demyelination. The prevalence of DPN ranges from 2.4% to 78.8% worldwide, depending on the diagnostic method and the population assessed (hospital-based or outpatients). Risk factors include age, male gender, duration of diabetes, uncontrolled glycaemia, height, overweight and obesity, and insulin treatment. Several diagnostic methods have been developed, and composite scores combined with nerve conduction studies are the most reliable to identify early DPN. Treatment should be directed to improve etiologic factors besides reducing symptoms; several approaches have been evaluated to reduce neuropathic impairments and improve nerve conduction, such as oral antidiabetics, statins, and antioxidants (alpha-lipoic acid, ubiquinone, and flavonoids).

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“…Ezetimibe is a comparatively new cholesterol-lowering drug with a different mechanism from statins [15], and thus could provide another quality lipid control treatment. It reduces cholesterol by inhibiting the absorption of LDL-C from the intestinal mucous membrane.…”

Section: Discussionmentioning

confidence: 99%

Impact of combination therapy with statin and ezetimibe on secondary prevention for post-acute myocardial infarction patients in the statin era

Ebisawa

Izawa

Ueki

et al. 2015

IJC Heart & Vasculature

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BackgroundLittle is known concerning the effect of ezetimibe for secondary prevention in post-myocardial infarction (MI) patients. In this study, we investigated the secondary prevention effect of ezetimibe for post-MI patients.MethodsThis study is a retrospective analysis of Assessing Lipophilic vs. hydrophilic Statin therapy for Acute MI (ALPS-AMI study). The patients were divided into two groups: those administered a statin to control low density lipoprotein-cholesterol (LDL-C), the ezetimibe(−) group, and those administered ezetimibe in addition to a statin to control LDL-C, the ezetimibe(+) group. The endpoints were Major Adverse Cardiac and Cerebrovascular Event (MACCE), including all-cause death, recurrence of MI, stroke, and heart failure requiring hospitalization, and MACCE with revascularization.ResultsThe ezetimibe(+) and ezetimibe(−) groups contained 113 and 337 patients, respectively. Incidences of MACCE and MACCE with revascularization were lower in the ezetimibe(+) group than in the ezetimibe(−) group (2.6% vs. 11.5%, p = 0.002; 23.0% vs. 36.7%, p = 0.014, respectively). Moreover, logistic regression analysis revealed ezetimibe(+) was a significant negative predictor of MACCE (OR 0.208, 95% CI 0.048 to 0.903, p = 0.047) and MACCE with revascularization (OR 0.463, 95% CI 0.258 to 0.831, p = 0.008). The preventive effect of ezetimibe against MACCE was observed in both moderate- and high-intensity lipid lowering treatment groups (0% vs. 17%; p = 0.077, 3.1% vs. 9.4%; p = 0.033).ConclusionsIn lipid-lowering therapy post-MI, ezetimibe and statin combination therapy improved MACCE with or without revascularization compared with statin monotherapy. These findings suggest that post-MI secondary prevention should be more intensive.

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Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin

Cited by 44 publications

References 31 publications

Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe

Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe

Diabetic Polyneuropathy in Type 2 Diabetes Mellitus: Inflammation, Oxidative Stress, and Mitochondrial Function

Impact of combination therapy with statin and ezetimibe on secondary prevention for post-acute myocardial infarction patients in the statin era

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