A Phase III, Multicenter, Randomized, Double-blind, Active Comparator Clinical Trial to Compare the Efficacy and Safety of Combination Therapy With Ezetimibe and Rosuvastatin Versus Rosuvastatin Monotherapy in Patients With Hypercholesterolemia: I-ROSETTE (Ildong Rosuvastatin &amp; Ezetimibe for Hypercholesterolemia) Randomized Controlled Trial

Hong, Soon Jun; Jeong, Han Saem; Ahn, Jin‐Chul; Hun, Dong; Won, Kyung Heon; Kim, Weon; Cho, Sang Kyoon; Kim, Seok Yeon; Yoo, Byung Su; Sung, Ki Chul; Rha, Seung Woon; Shin, Joon Han; Han, Kyoo Rok; Chung, Wook Sung; Hyon, Min Su; Lee, Han Cheol; Bae, Jang Ho; Rhee, Moo Yong; Kwan, Jun; Jeon, Dong Woon; Yoo, Ki Dong; Kim, Hyo Soo

doi:10.1016/j.clinthera.2017.12.018

Cited by 45 publications

(53 citation statements)

References 35 publications

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“…Overall, results were also similar to those of other past studies. LDL-C lowering was consistent with that reported in previous studies including RCTs that did not meet our inclusion criteria and pooled analyses [11,24]. The low variability of LDL-C lowering with the addition of ezetimibe to statin therapy is in line with a previous report by Descamps et al [25].…”

Section: Discussionsupporting

confidence: 91%

Lipid-Lowering Efficacy of Ezetimibe in Patients with Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analyses

Shaya

Sing

Milam³

et al. 2019

Am J Cardiovasc Drugs

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Introduction Patients with atherosclerotic cardiovascular disease (ASCVD), especially those with recent (< 1 year) acute coronary syndrome (ACS), are at high risk for recurrent cardiovascular events. This risk can be reduced by lowering lowdensity lipoprotein cholesterol (LDL-C) levels. A comprehensive meta-analysis on the LDL-C-lowering efficacy of ezetimibe is lacking. This study attempts to address this gap. Methods A systematic literature review of randomized controlled trials evaluating the LDL-C-lowering efficacy of ezetimibe in the ASCVD population was conducted. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for publications from database inception to August 2018 and for conference abstracts from 2015 to August 2018. Meta-analyses were conducted to evaluate the LDL-C-lowering efficacy of ezetimibe in the ASCVD population and the recent ACS subgroup. Results In total, 12 studies were eligible for the meta-analyses. Treatment with combination ezetimibe plus statin therapy showed greater absolute LDL-C reduction than statin monotherapy (mean difference − 21.86 mg/dL; 95% confidence interval [CI] − 26.56 to − 17.17; p < 0.0001) after 6 months of treatment (or at a timepoint closest to 6 months). Similarly, in patients with recent ACS, combination ezetimibe plus statin therapy was favorable compared with statin monotherapy (mean treatment difference − 19.19 mg/dL; 95% CI − 25.22 to − 13.16; p < 0.0001). Conclusions Ezetimibe, when added to statin therapy, provided a modest additional reduction in LDL-C compared with statin monotherapy. However, this may not be sufficient for some patients with ASCVD who have especially high LDL-C levels despite optimal statin therapy.

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Section: Discussionsupporting

confidence: 91%

Lipid-Lowering Efficacy of Ezetimibe in Patients with Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analyses

Shaya

Sing

Milam³

et al. 2019

Am J Cardiovasc Drugs

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“…Finally, 11 studies (n = 1926 participants) were eligible for the meta-analysis ( Fig. 1) [13][14][15][16][17][18][19][20][21][22][23].…”

Section: Study Selectionmentioning

confidence: 99%

Efficacy of combination therapy with ezetimibe and statins versus a double dose of statin monotherapy in participants with hypercholesterolemia: a meta-analysis of literature

et al. 2020

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Background: The aim of this study was to compare and summarize the lipid-altering effects of combination therapy with ezetimibe and statins (E/S) and a double dose of statin (D/S) monotherapy on patients with hypercholesterolemia. Methods: We conducted search on 2 medical databases, PubMed and EMBASE to identify all relevant studies. A meta-analysis was performed to clarify the efficacy in the two groups. Only double-blind Randomized controlled study (RCTs) of efficacy evaluation in the two groups with ezetimibe and statins and a double dose of statin in participants with hypercholesterolemia that examined low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein (HDL) were included. Two reviewers extracted data from all primary studies independently. The primary data were the level of LDL-C, TC and HDL-C concentrations at the end point and are expressed as mean and standard deviation (SD). Results: A total of 11 double-blind, active or placebo-controlled studies with 1926 hypercholesterolemia adults randomized to ezetimibe 10 mg added to ongoing statins (N = 994) or statin titration (doubling) (N = 932) were pooled for the global meta-analysis. The effect size between treatment groups within individual studies was assessed by weighted mean difference (MD) using a random-or fixed-effect model. The result showed that the participants in E/S group get obvious lower LDL-C [MD =-13.14 mg/dL, 95%CI (−16.83,-9.44), p = 0.00001] and TC concentration [MD =-23.79 mg/dL, 95%CI (−38.65,-8.93), p = 0.002] from baseline to follow-up, comparing to the D/ S group. Besides, no significant between-group differences were observed for concentrations of HDL-C [MD = 0.46 mg/dL, 95%CI (− 1.14, 2.06), p = 0.57]. According to subgroup analysis, the combination of ezetimibe and atorvastatin (10 mg) [MD =-16.98 mg/dL, p < 0 .0001] or simvastatin (20 mg) [MD =-17.35 mg/dL, p < 0 .0001] showed stronger ability of reducing LDL-C than combination of ezetimibe and rosuvastatin (10 mg) [MD =-9.29 mg/dL, p = 0.05]. The efficacy of short-term (endpoint time between 6 to 16 week) and long-term (52 week) treatment in the LDL-C between two groups did not show significant differences. Besides, only participants from Asia treated with combination therapy were associated with a significant lower LDL-C concentration [MD =-14.7 mg/dL, p < 0 .0001].

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“…The LDL-C-lowering efficacy of each of the ezetimibe/rosuvastatin combinations was superior to that of each of the respective doses of rosuvastatin. 22 …”

Section: Combination Therapy: Ezetimibe Add-on To Statinmentioning

confidence: 99%

Adding ezetimibe to statin therapy: latest evidence and clinical implications

Vavlukis¹,

Vavlukis²

2018

DIC

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BackgroundStatins are the hypolipemic treatment of choice for hyperlipidemia with confirmed atherosclerotic cardiovascular disease (ASCVD) protective effect, proven even in normolipemic patients. But in rare situations, even with a high-dose treatment regimen, or maximally tolerated statin dose treatment, treatment targets of low-density lipoprotein cholesterol (LDL-C), according to the risk profile of the patient, cannot be achieved. Combination therapy with ezetimibe is an effective treatment choice, as it is one of the few hypolipemic drugs with proven ASCVD protective effect.AimIn this review, we address the question of therapeutic efficacy and safety of ezetimibe in combination therapy with statins, as expressed through its hypolipemic and vasoprotective effects and its potential side effects.MethodsWe conducted a literature review of English articles through PubMed, PubMed Central, and Cochrane for randomized clinical trials, retrospective analyses, meta-analyses, and review articles by using key words: ezetimibe, statins, combination therapy, adverse effects. We analyzed data on ezetimibe–statin combination therapy in terms of hypolipemic efficacy, ASCVD risk reduction, and adverse effects.ResultsStatins have been proven to be very effective in reducing ASCVD risk, with no apparent threshold at which LDL-C lowering is not associated with reduced risk. Yet, a significant on-treatment residual risk of major cardiovascular (CV) events still exists according to meta-analyses of statin trials. Findings like this point to the unmet needs of the patients on statin treatment. The unmet needs in terms of LDL-C targets and ASCVD risk reduction raise the question of statin combination therapy. Ezetimibe is a cholesterol-lowering drug from the class of cholesterol absorption inhibitors, with the potency to decrease LDL-C by about 10–18% and Apo B by 11–16%, while in combination therapy with statins, an additional LDL-C lowering of 25% or total LDL-C lowering of 34–61% is observed. The effects on LDL-C and other lipoprotein (LP) fractions are translated by ASCVD risk reduction. Ezetimibe is one of the few hypolipemic medications that leads to additional ASCVD risk reduction when added to statin therapy. Present data on ezetimibe support the existence of pleotropic anti-inflammatory and antioxidative effects, in addition to its hypolipemic effect, which are responsible for this added ASCVD risk reduction on top of statin monotherapy. Ezetimibe, in combination therapy with a maximal or maximally tolerated statin therapy, is used in patients who fail to achieve target LDL-C levels with statin monotherapy. In combination with low-to-moderate statin dose treatment, or with second- or third-line statins, ezetimibe is used in situations of statin-associated muscle symptoms. The combination therapy is relatively safe.ConclusionEzetimibe add-on to statin combination therapy is an effective treatment option that leads to additional LDL-C lowering – recommended in situations where, with a maximal or maximally tolerated statin mon...

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Cited by 45 publications

References 35 publications

Lipid-Lowering Efficacy of Ezetimibe in Patients with Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analyses

Lipid-Lowering Efficacy of Ezetimibe in Patients with Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analyses

Efficacy of combination therapy with ezetimibe and statins versus a double dose of statin monotherapy in participants with hypercholesterolemia: a meta-analysis of literature

Adding ezetimibe to statin therapy: latest evidence and clinical implications

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