Effects of Ezetimibe-Statin Combination Therapy on Coronary Atherosclerosis in Acute Coronary Syndrome

Hibi, Kiyoshi; Sonoda, Shinjo; Kawasaki, Masanori; Otsuji, Yutaka; Murohara, Toyoaki; Ishii, Hideki; Sato, Katsuhiko; Koshida, Ryoji; Ozaki, Yukio; Sata, Masataka; Morino, Yoshihiro; Miyamoto, Tadashi; Amano, Tetsuya; Morita, Satoshi; Kozuma, Ken; Kimura, Kazuo; Fujiwara, Hisayoshi; Investigators, Ezetimibe-ACS

doi:10.1253/circj.cj-17-0598

Cited by 37 publications

(32 citation statements)

References 35 publications

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“…A large body of evidence supports a central role for LDL-C lowering in the prevention of atherosclerotic cardiovascular disease [41]. It is proven that the process of atherosclerosis strongly depends on LDL-C, but whether or not this dependence is similar in statin regimens and dual therapy regimens is less defined [17,18]. It is therefore reasonable to think that the effects of the ezetimibestatin combination therapy can vary according to the patient sample (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, many studies have investigated the reduction of LDL-C with nonstatin drugs and Its impact on atherosclerosis regression. However, the studies were mostly small and their results were not always robust [14][15][16][17][18][19][20][21]. A previously published meta-analysis showed an association between the regression of atheroma volume with the addition of ezetimibe [22].…”

Section: Introductionmentioning

confidence: 99%

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Role of non-statin lipid-lowering therapy in coronary atherosclerosis regression: a meta-analysis and meta-regression

Masson

Lobo²,

Siniawski

et al. 2020

Lipids Health Dis

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Background: Several studies have investigated the association between non-statin lipid-lowering therapy and regression of atherosclerosis. However, these studies were mostly small and their results were not always robust. The objectives were: (1) to define if a dual lipid-lowering therapy (statin + non-statin drugs) is associated with coronary atherosclerosis regression, estimated by intravascular ultrasound (IVUS); (2) to assess the association between dual lipid-lowering-induced changes in low density lipoprotein cholesterol (LDL-C) and non-high-densitylipoprotein cholesterol (non-HDL-C) levels and atherosclerosis regression. Methods: A meta-analysis including trials of non-statin lipid-lowering therapy, reporting LDL-C, non-HDL-C and total atheroma volume (TAV) with a minimum of 6 months of follow-up was performed. The primary endpoint was defined as the change in TAV measured from baseline to follow-up, comparing groups of subjects on statins alone versus combination of statin and non-statin drugs. The random-effects model and meta-regression were performed. Results: Eight eligible trials of non-statin lipid-lowering drugs (1759 patients) were included. Overall, the dual lipidlowering therapy was associated with a significant reduction in TAV [− 4.0 mm 3 (CI 95%-5.4 to − 2.6)]; I 2 = 0%]. The findings were similar in the stratified analysis according to the lipid-lowering drug class (ezetimibe or PCSK9 inhibitors). In the meta-regression, a 10% decrease in LDL-C or non-HDL-C levels, was associated, respectively, with 1.0 mm 3 and 1.1 mm 3 regressions in TAV. Conclusion: These data suggests the addition of ezetimibe or PCSK9 inhibitors to statin therapy results in a significant regression of TAV. Reduction of coronary atherosclerosis observed with non-statin lipid-lowering therapy is associated to the degree of LDL-C and non-HDL-C lowering. Therefore, it seems reasonable to achieve lipid goals according to cardiovascular risk and regardless of the lipid-lowering strategy used (statin monotherapy or dual treatment).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of non-statin lipid-lowering therapy in coronary atherosclerosis regression: a meta-analysis and meta-regression

Masson

Lobo²,

Siniawski

et al. 2020

Lipids Health Dis

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“…[ 23 ] However, whether the combination therapy had a superior effect on stabilizing coronary VP, especially increasing the FCT remains unclear. [ 24 – 26 ] Few studies have evaluated the effect of combination therapy on the FCT of VPs. One study showed that when ezetimibe was combined with statin, it could further increase the FCT more than statin monotherapy [ 27 ] ; this finding is similar to our result.…”

Section: Discussionmentioning

confidence: 99%

Intensive statin versus low-dose statin + ezetimibe treatment for fibrous cap thickness of coronary vulnerable plaques

Meng

Yin

Lü

et al. 2020

Chinese Medical Journal

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Background Acute coronary syndromes mainly result from abrupt thrombotic occlusion caused by atherosclerotic vulnerable plaques (VPs) that suddenly rupture or erosion. Fibrous cap thickness (FCT) is a major determinant of the propensity of a VP to rupture and is recognized as a key factor. The intensive use of statins is known to have the ability to increase FCT; however, there is a risk of additional adverse effects. However, lower dose statin with ezetimibe is known to be tolerable by patients. The present study aimed to investigate the effect of intensive statin vs. low-dose stain + ezetimibe therapy on FCT, as evaluated using optical coherence tomography. Method Patients who had VPs (minimum FCT <65 μm and lipid core >90°) and deferred from intervention in our single center from January 2014 to December 2018 were included in the trial. They were divided into the following two groups: intensive statin group (rosuvastatin 15–20 mg or atorvastatin 30–40 mg) and combination therapy group (rosuvastatin 5–10 mg or atorvastatin 10–20 mg + ezetimibe 10 mg). At the 12-month follow-up, we compared the change in the FCT (ΔFCT%) between the two groups and analyzed the association of ΔFCT% with risk factors. Fisher exact test was used for all categorical variables. Student's t test or Mann-Whitney U -test was used for analyzing the continuous data. The relationship between ΔFCT% and risk factors was analyzed using linear regression analysis. Result Total 53 patients were finally enrolled, including 26 patients who were in the intensive statin group and 27 who were in the combination therapy group. At the 12-month follow-up, the serum levels of total cholesterol (TC), total triglyceride, low-density lipoprotein (LDL-C), hypersensitive C-reactive protein (hs-CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels were reduced in both the groups. The ΔTC%, ΔLDL-C%, and ΔLp-PLA2% were decreased further in the combination therapy group. FCT was increased in both the groups (combination treatment group vs . intensive statin group: 128.89 ± 7.64 vs. 110.19 ± 7.00 μm, t = −9.282, P < 0.001) at the 12-month follow-up. The increase in ΔFCT% was more in the combination therapy group (123.46% ± 14.05% vs. 91.14% ± 11.68%, t = −9.085, P < 0.001). Based on the multivariate linear regression analysis, only the serum Lp-PLA2 at the 12-month follow-up ( B = −0.203, t = −2.701, P = 0.010), ΔTC% ( B = −0.573, t = −2.048, P = 0.046), and Δhs-CRP % ( B = −0.30...

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“…a 115 records were manually entered, and four additional records were cited in protocols. ASCVD atherosclerotic cardiovascular disease, LDL-C low-density lipoprotein cholesterol [27], randomized patients included in the full analysis set; Masuda et al [29], randomized patients included in the primary analysis; Ueda et al [32], randomized patients who were included in the analysis; Wang et al [34], randomized patients included in the analysis; West et al [35], randomized patients included in the analysis Analyses of studies according to whether patients were statin naïve or had a history of statin therapy at enrollment showed that patients receiving combination ezetimibe plus statin therapy had greater LDL-C reduction than those receiving statin monotherapy, irrespective of prior history of statin therapy (mean difference − 25.07 mg/dL; 95% CI − 31.73 to − 18.41 and − 19.54 mg/dL; 95% CI − 25.56 to − 13.53, respectively; Fig. S5 in the ESM).…”

Section: Efficacy Of Low-density Lipoprotein Cholesterol Lowering Of mentioning

confidence: 99%

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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Effects of Ezetimibe-Statin Combination Therapy on Coronary Atherosclerosis in Acute Coronary Syndrome

Cited by 37 publications

References 35 publications

Role of non-statin lipid-lowering therapy in coronary atherosclerosis regression: a meta-analysis and meta-regression

Role of non-statin lipid-lowering therapy in coronary atherosclerosis regression: a meta-analysis and meta-regression

Intensive statin versus low-dose statin + ezetimibe treatment for fibrous cap thickness of coronary vulnerable plaques

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

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