Treatment With Ezetimibe Plus Low-Dose Atorvastatin Compared With Higher-Dose Atorvastatin Alone

Piorkowski, Michael; Fischer, Sabine; Stellbaum, Caroline; Jaster, Markus; Martus, Peter; Morguet, Andreas J.; Schultheiss, Heinz‐Peter; Rauch, Ursula

doi:10.1016/j.jacc.2006.10.064

Cited by 88 publications

(61 citation statements)

References 41 publications

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“…(16) In addition, studies have reported that during a four-week treatment period, the degree of LDL-C reduction achieved by 40 mg/day of atorvastatin was comparable with that obtained by 10 mg/day of ezetimibe in combination with 10 mg/day of atorvastatin. (23) In our study, the proportion of patients achieving NCEP-ATP III LDL-C target levels with combination treatment was also similar to that of other reports. (24)(25)(26)(27) The decrease in LDL-C with combination treatment has been consistently reported across trials.…”

Section: Discussionsupporting

confidence: 91%

Hypolipidaemic and anti-inflammatory effects of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia

Padhy¹,

Yadav²,

Gupta³

2013

SMedJ

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ResUlTsOf the 30 patients, 10 men and 5 women (mean age 54.3 ± 1.6 years) received ezetimibe plus atorvastatin, while 13 men and 2 women (mean age 53.7 ± 2.8 years) received only atorvastatin. The combination treatment significantly reduced total cholesterol (percentage treatment difference −14.4 ± 6.5, 95% confidence interval [CI] −1.0 to −27.7; p = 0.041) and LDL cholesterol (LDL-C; percentage treatment difference −19.9 ± 6.1, 95% CI −7.4 to −32.4; p = 0.003) compared to atorvastatin monotherapy. 13 patients on combination treament achieved the National Cholesterol Education Program target for LDL-C as compared to 9 patients on atorvastatin monotherapy (p = 0.032). Significant reductions in very low-density lipoprotein cholesterol, triglyceride, ox-LDL and sICAM were observed with combination treatment compared to atorvastatin monotherapy. However, no significant change was seen in high-density lipoprotein cholesterol or hsCRP levels between the two groups.CONClUsION Combination treatment with atorvastatin and ezetimibe had relatively better lipid-lowering and antiinflammatory efficacy than atorvastatin monotherapy. Keywords: atorvastatin, ezetimibe, high sensitivity C-reactive protein, intercellular cell adhesion moleculeSingapore Med J 2013; 54(2): 90-95

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Section: Discussionsupporting

confidence: 91%

Hypolipidaemic and anti-inflammatory effects of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia

Padhy¹,

Yadav²,

Gupta³

2013

SMedJ

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“…In patients with heart failure, 4 weeks of simvastatin but not ezetimibe treatment improved endothelial function and reduced oxidative stress, despite comparable reduction in serum cholesterol levels [32]. Furthermore, compared with patients receiving combination therapy of ezetimibe and statin, patients receiving a higher dose of statin to achieve equal levels of cholesterol lowering have greater improvement in endothelial function [33] and lower platelet activation and chemokine levels [34]. Thus, the LDL-lowering benefits of ezetimibe remain to be determined.…”

Section: Clinical Trials With Statinsmentioning

confidence: 99%

Pleiotropic effects of statin therapy: molecular mechanisms and clinical results

Wang

Liu

Liao

2008

Trends in Molecular Medicine

538

394

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Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which is required for cholesterol biosynthesis, and are beneficial in the primary and secondary prevention of cardiovascular disease. Most of the benefits of statin therapy are owing to the lowering of serum cholesterol levels. However, by inhibiting HMG-CoA reductase, statins can also inhibit the synthesis of isoprenoids, which are important lipid attachments for intracellular signaling molecules, such as Rho, Rac and Cdc42. Therefore, it is possible that statins might exert cholesterol-independent or 'pleiotropic' effects through direct inhibition of these small GTP-binding proteins. Recent studies have shown that statins might have important roles in diseases that are not mediated by cholesterol. Here, we review data from recent clinical trials that support the concept of statin pleiotropy and provide a rationale for their clinical importance. [6], have demonstrated the beneficial effects of statin therapy for primary and secondary prevention of cardiovascular disease. Because 60-70% of serum cholesterol is derived from hepatic synthesis and HMG-CoA reductase is the crucial, rate-limiting enzyme in the cholesterol biosynthetic pathway, inhibition of this enzyme by statins results in a dramatic reduction in circulating low-density lipoprotein (LDL)-cholesterol (Figure 1). In addition, reduction of LDL-cholesterol leads to upregulation of the LDL receptor and increased LDL clearance. The lowering of serum cholesterol levels is therefore thought to be the primary mechanism underlying the therapeutic benefits of statin therapy in cardiovascular disease [1]. Pleiotropy of statins: beyond cholesterol loweringStatins, however, might also exert cholesterol-independent or pleiotropic effects. By inhibiting the conversion of HMG-CoA to L-mevalonic acid, statins prevent the synthesis of important isoprenoids, such as farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP), which are precursors of cholesterol biosynthesis [7] (Figure 1). These intermediates serve as important lipid attachments for the post-translational modification of proteins, such as nuclear lamins, Ras, Rho, Rac and Rap [8]. These isoprenylated proteins constitute approximately 2% of total cellular proteins [9]. Protein isoprenylation (see Glossary) enables proper subcellular localization and trafficking of intracellular proteins. Given that isoprenylated proteins might

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“…The differences may be attributed to the length of atorvastatin treatment before PCI and the sample size. Nevertheless, dose-dependent antiplatelet and antiinflammatory effects of atorvastatin have been demonstrated (17). For ACS patients, the thrombogenesis and inflammatory reactions are closely related to the PCI-related myocardial damages, and our results indicate that a high dose of atorvastatin should be given before PCI.…”

Section: Data Presented As N (%) or Mean ± Sdmentioning

confidence: 59%

Effect of different loading doses of atorvastatin on percutaneous coronary intervention for acute coronary syndromes

Sun

Gao

et al. 2010

Canadian Journal of Cardiology

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Treatment With Ezetimibe Plus Low-Dose Atorvastatin Compared With Higher-Dose Atorvastatin Alone

Cited by 88 publications

References 41 publications

Hypolipidaemic and anti-inflammatory effects of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia

Hypolipidaemic and anti-inflammatory effects of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia

Pleiotropic effects of statin therapy: molecular mechanisms and clinical results

Effect of different loading doses of atorvastatin on percutaneous coronary intervention for acute coronary syndromes

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