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. 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

Effect of ezetimibe on plasma adipokines: a systematic review and meta‐analysis

“…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 .…”

“…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 .…”

“…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 .…”

“…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 .…”

“…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 ).…”