Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe
Abstract: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. Th… Show more
“…The afore‐mentioned four studies had high risks of bias regarding allocation concealment , while the others had a lack of information on this aspect . Several studies showed a high risk of bias with respect to the blinding of participants, personnel and outcome assessors , and some contained insufficient information . Most of the included studies had a low risk of bias regarding incomplete outcome data, and only two exhibited a high risk of bias .…”
Section: Resultsmentioning
confidence: 99%
“…The clinical trials used different doses of ezetimibe and statins. Two studies investigated ezetimibe 5 mg day –1 and 21 studies investigated ezetimibe 10 mg day –1 ; in regard to statins, one study investigated atorvastatin 5 mg day –1 , one study investigated atorvastatin 10 mg day –1 , two studies investigated atorvastatin 20 mg day –1 , two studies investigated atorvastatin 80 mg day –1 , one study investigated fluvastatin 30 mg day –1 , one study investigated lovastatin 5 mg day –1 , one study investigated lovastatin 20 mg day –1 , one study investigated rosuvastatin 2.5 mg day –1 , one study investigated rosuvastatin 10 mg day –1 , two studies investigated simvastatin 10 mg day –1 , one study investigated simvastatin 20 mg day –1 , seven studies investigated simvastatin 40 mg day –1 and two studies investigated simvastatin 80 mg day –1 . The range of intervention periods was from 2 weeks up to 12 months .…”
Section: Resultsmentioning
confidence: 99%
“…The range of intervention periods was from 2 weeks up to 12 months . Study designs of the included studies included parallel group and crossover . Selected studies enrolled subjects with diabetes , prediabetes , chronic kidney disease , obesity , abdominal aortic aneurysm , a high risk of cardiovascular disease , dyslipidaemia , stable angina pectoris , non‐alcoholic fatty liver disease , metabolic syndrome , acute coronary syndrome , coronary artery disease and also apparently healthy men .…”
Section: Resultsmentioning
confidence: 99%
“…With respect to random sequence generation, four studies were judged to have a high risk of bias , while some studies presented insufficient information . The afore‐mentioned four studies had high risks of bias regarding allocation concealment , while the others had a lack of information on this aspect .…”
Section: Resultsmentioning
confidence: 99%
“…However, significantly greater reductions in the plasma concentrations of TNF‐α (SMD –0.48, 95% CI –0.87, −0.08; P = 0.018; I 2 = 75.43%; Figure ) were achieved with ezetimibe/statin combination therapy. In the sensitivity analysis, omission of each study from the meta‐analysis did not remove the statistical significance of effect size, apart from in the study by Yamazaki et al , for which a slight sensitivity was observed (Figure ).…”
The results suggested that ezetimibe add-on to statin therapy is associated with an enhanced TNF-α-lowering effect compared with statin monotherapy. Owing to the emerging role of TNF-α in the pathogenesis of metabolic disorders, further investigations are required to unveil the translational relevance of this TNF-α-lowering effect.
“…The afore‐mentioned four studies had high risks of bias regarding allocation concealment , while the others had a lack of information on this aspect . Several studies showed a high risk of bias with respect to the blinding of participants, personnel and outcome assessors , and some contained insufficient information . Most of the included studies had a low risk of bias regarding incomplete outcome data, and only two exhibited a high risk of bias .…”
Section: Resultsmentioning
confidence: 99%
“…The clinical trials used different doses of ezetimibe and statins. Two studies investigated ezetimibe 5 mg day –1 and 21 studies investigated ezetimibe 10 mg day –1 ; in regard to statins, one study investigated atorvastatin 5 mg day –1 , one study investigated atorvastatin 10 mg day –1 , two studies investigated atorvastatin 20 mg day –1 , two studies investigated atorvastatin 80 mg day –1 , one study investigated fluvastatin 30 mg day –1 , one study investigated lovastatin 5 mg day –1 , one study investigated lovastatin 20 mg day –1 , one study investigated rosuvastatin 2.5 mg day –1 , one study investigated rosuvastatin 10 mg day –1 , two studies investigated simvastatin 10 mg day –1 , one study investigated simvastatin 20 mg day –1 , seven studies investigated simvastatin 40 mg day –1 and two studies investigated simvastatin 80 mg day –1 . The range of intervention periods was from 2 weeks up to 12 months .…”
Section: Resultsmentioning
confidence: 99%
“…The range of intervention periods was from 2 weeks up to 12 months . Study designs of the included studies included parallel group and crossover . Selected studies enrolled subjects with diabetes , prediabetes , chronic kidney disease , obesity , abdominal aortic aneurysm , a high risk of cardiovascular disease , dyslipidaemia , stable angina pectoris , non‐alcoholic fatty liver disease , metabolic syndrome , acute coronary syndrome , coronary artery disease and also apparently healthy men .…”
Section: Resultsmentioning
confidence: 99%
“…With respect to random sequence generation, four studies were judged to have a high risk of bias , while some studies presented insufficient information . The afore‐mentioned four studies had high risks of bias regarding allocation concealment , while the others had a lack of information on this aspect .…”
Section: Resultsmentioning
confidence: 99%
“…However, significantly greater reductions in the plasma concentrations of TNF‐α (SMD –0.48, 95% CI –0.87, −0.08; P = 0.018; I 2 = 75.43%; Figure ) were achieved with ezetimibe/statin combination therapy. In the sensitivity analysis, omission of each study from the meta‐analysis did not remove the statistical significance of effect size, apart from in the study by Yamazaki et al , for which a slight sensitivity was observed (Figure ).…”
The results suggested that ezetimibe add-on to statin therapy is associated with an enhanced TNF-α-lowering effect compared with statin monotherapy. Owing to the emerging role of TNF-α in the pathogenesis of metabolic disorders, further investigations are required to unveil the translational relevance of this TNF-α-lowering effect.
BackgroundIt remains controversial whether adding ezetimibe to low/moderate‐intensity statins has a more beneficial impact on the treatment efficacy and safety of patients with existing atherosclerotic cardiovascular disease (ASCVD) compared to high‐intensity statin regimens.HypothesisA combination of low/moderate‐intensity statins plus ezetimibe might be more effective and safer than high‐intensity statin monotherapy.MethodsWe searched databases for randomized controlled trials comparing lipid profile alterations, drug‐related adverse events, and MACE components between high‐intensity statin monotherapy and low/moderate‐intensity statin plus ezetimibe combination therapy. Pooled risk ratios (RR), mean differences (MD), and 95% confidence intervals (95% CI) were estimated using a random‐effects model.ResultsOur comprehensive search resulted in 32 studies comprising 6162 patients treated with monotherapy against 5880 patients on combination therapy. Combination therapy was more effective in reducing low‐density lipoprotein cholesterol (LDL‐C) levels compared to monotherapy (MD = −6.6, 95% CI: −10.6 to −2.5); however, no significant differences were observed in other lipid parameters. Furthermore, the combination therapy group experienced a lower risk of myalgia (RR = 0.27, 95% CI: 0.13–0.57) and discontinuation due to adverse events (RR = 0.61, 95% CI: 0.51–0.74). The occurrence of MACE was similar between the two treatment groups.ConclusionsAdding ezetimibe to low/moderate‐intensity statins resulted in a greater reduction in LDL‐C levels, a lower rate of myalgia, and less drug discontinuation compared to high‐intensity statin monotherapy in patients with existing cardiovascular disease. However, according to our meta‐analysis, the observed reduction in LDL‐C levels in the combination group did not correlate with a reduction in MACE compared to the high‐intensity statin group.
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