The safety and efficacy of Ezetimibe Plus Statins on ASVD and Related Diseases.
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ABSTRACT:
SUBMITTER: Wan S
PROVIDER: S-EPMC8612613 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC11319735 | biostudies-literature
Project description:AIM:The purpose of this study is to evaluate the therapeutic efficacy and safety of iguratimod plus corticosteroid as bridge therapy in the treatment of mild immunoglobulin G4-related disease (IgG4-RD). METHODS:Newly diagnosed IgG4-RD patients, without internal organ involvement were enrolled. Patients were given one dose of diprospan, intramuscular injection, and iguratimod, 25 mg, twice daily, for 24 weeks and were followed up at 0, 12 and 24 weeks. Follow-up indexes included IgG4-RD responder index (IgG4-RD RI), serology and imaging, plasma cytokines and adverse drug effect. Flow cytometry was performed for T, B cell subsets and plasma was collected for liquid chromatography mass spectrometry (LC-MS)-based metabolomic profiling and data processing. RESULTS:Thirty patients were enrolled. At week 24, 9 (30.0%) patients achieved complete response, 17 (56.7%) patients with partial response, and 4 (13.3%) patients had no response to treatment. IgG4-RD RI, serum IgG and IgG4 levels decreased significantly at weeks 12 and 24 after treatment, as well as CD3+ CD8+ T cells, plasmablast/plasma cells and memory B cells. The LC-MS based plasma metabolomic profiles revealed significant changes between untreated patients and healthy donors, which became much similar to normal states after treatment. CONCLUSION:Iguratimod plus corticosteroid as bridge therapy is effective for the treatment of mild IgG4-RD, it can improve the clinical symptoms, reduce serum IgG and IgG4 levels, especially plasmablasts/plasma cells and memory B cells. In addition, the metabolite profiling became similar to normal controls after treatment.
| S-EPMC6772123 | biostudies-literature
Project description:ObjectiveStatins are sometimes associated with worsened glycemic control. Patients with type 2 diabetes mellitus (T2DM) may require non-statin therapies to achieve low-density lipoprotein cholesterol (LDL-C) lowering goals. This study evaluated the efficacy and safety of bempedoic acid 180 mg plus ezetimibe 10 mg fixed-dose combination (BA + EZE FDC) in patients with T2DM and hypercholesterolemia who were not receiving background statins or other lipid-lowering therapy.MethodsPatients with T2DM and elevated LDL-C levels were enrolled into this phase 2, double-blind study (NCT03531905). Patients received placebo during a 5-week washout period where background lipid-lowering therapies (including statins) were discontinued. Eligible patients were then randomized 1:1:1 to receive either BA + EZE FDC, ezetimibe 10 mg, or placebo once daily for 12 weeks. Assessments included the percent change from baseline to week 12 in LDL-C, other lipid parameters, and high-sensitivity C-reactive protein (hsCRP); and the monitoring of safety and tolerability.ResultsAmong 179 randomized patients, baseline characteristics following the washout period were similar across treatment groups, with mean LDL-C levels of 142.6 mg/dL and mean glycated hemoglobin of 8.0%. At week 12, BA + EZE FDC therapy lowered mean LDL-C levels by 38.8%, significantly more than ezetimibe alone (19.2%; difference, 19.5% [95% confidence interval (CI), 13.4%-25.7%]; p < 0.001) or placebo (increase of 0.9%; difference, 39.6% [95% CI, 33.4%-45.8%]; p < 0.001). BA + EZE FDC significantly reduced hsCRP levels from baseline vs ezetimibe (29.2%; p = 0.005) and vs placebo (36.7%; p < 0.001). Incidence of treatment-emergent adverse events was low in all treatment groups, with no indication of worsened glycemic control.ConclusionIn patients with T2DM and hypercholesterolemia who were not receiving statins or other lipid-lowering drugs, BA + EZE FDC significantly lowered LDL-C levels and was generally well tolerated.
| S-EPMC8550983 | biostudies-literature
Project description:BackgroundReducing low-density lipoprotein cholesterol (LDL-C) is associated with reduced risk for major coronary events. Despite statin efficacy, a considerable proportion of statin-treated hypercholesterolemic patients fail to reach therapeutic LDL-C targets as defined by guidelines. This study compared the efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing statin in a population of Taiwanese patients with hypercholesterolemia.MethodsThis was a randomized, open-label, parallel-group comparison study of ezetimibe 10 mg added to ongoing statin compared with doubling the dose of ongoing statin. Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with previous statin treatment were randomized (N = 83) to ongoing statin + ezetimibe (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or 20/10 mg) or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin 20 mg or pravastatin 40 mg) for 8 weeks. Percent change in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides, and specified safety parameters were assessed at 4 and 8 weeks.ResultsAt 8 weeks, patients treated with statin + ezetimibe experienced significantly greater reductions compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026) and total cholesterol (20.8% vs 12.2%, p = 0.0003). Percentage of patients achieving treatment goal was greater for statin + ezetimibe (58.6%) vs doubling statin (41.2%), but the difference was not statistically significant (p = 0.1675). The safety and tolerability profiles were similar between treatments.ConclusionEzetimibe added to ongoing statin therapy resulted in significantly greater lipid-lowering compared with doubling the dose of statin in Taiwanese patients with hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing.Trial registrationRegistered at ClinicalTrials.gov: NCT00652327.
| S-EPMC3403927 | biostudies-literature
Project description:Statin is highly recommended for dyslipidemia to prevent atherosclerosis-related cardiovascular diseases and death. The aim of this study was to compare the efficacies and safeties of low/moderate-intensity statin plus ezetimibe combination therapy vs. high-intensity statin monotherapy. Meta-analysis was conducted on data included in published studies performed to compare the effects of the two treatments on lipid parameters and hs-CRP. Safety-related parameters were also evaluated. Eighteen articles were included in the meta-analysis. In terms of efficacy, low/moderate-intensity statin plus ezetimibe reduced LDL-C (SE = 0.307; 95% CI 0.153-0.463), TC (SE = 0.217; 95% CI 0.098-0.337), triglyceride (SE = 0.307; 95% CI 0.153-0.463), and hs-CRP (SE = 0.190; 95% CI 0.018-0.362) significantly more than high-intensity statin therapy. In terms of safety, the two treatments were not significantly different in terms of ALT elevation, but high-intensity statin increased AST and CK significantly more than combination therapy. This analysis indicates that low/moderate-intensity statin plus ezetimibe combined therapy is more effective and safer than high-intensity statin monotherapy, which suggests the addition of ezetimibe to statin should be preferred over increasing statin dose and that high-intensity statin should be used more carefully, especially in patients with related risks.
| S-EPMC8896700 | biostudies-literature
Project description:BackgroundThe introduction of a fixed-dose combination (FDC) is expected to improve treatment compliance.MethodsThere were 181 subjects who were randomized to three groups: ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg, ezetimibe-rosuvastatin 10/20 mg, and telmisartan 80 mg. The primary outcomes were change in mean sitting systolic blood pressure (MSSBP) and percentage change in low-density-lipoprotein cholesterol (LDL-C) compared to baseline at week 8.ResultsThe least-square mean (SE) in MSSBP changes between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the ezetimibe-rosuvastatin 10/20 mg group were -25.81 (2.34) mmHg and -7.66 (2.45) mmHg. There was a significant difference between the two groups (-18.15 (2.83) mmHg, 95% CI -23.75 to -12.56, p < 0.0001). Changes in least-square mean (SE) in LDL-C between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the telmisartan 80 mg group were -63.82 (2.87)% and -2.48 (3.12)%. A significant difference was observed between the two groups (-61.34 (3.33)%, 95% CI -67.91 to -54.78, p < 0.0001). No serious adverse events were observed.ConclusionsEzetimibe-rosuvastatin plus telmisartan treatment is effective and safe when compared to either ezetimibe-rosuvastatin or telmisartan.
| S-EPMC10053813 | biostudies-literature
Project description:ObjectiveThe appropriate use of statins plays a vital role in reducing the risk of atherosclerotic cardiovascular disease (ASCVD). However, due to changes in diet and lifestyle, there has been a significant increase in the number of individuals with high cholesterol levels. Therefore, it is crucial to ensure the rational use of statins. Adverse reactions associated with statins, including liver enzyme abnormalities and statin-associated muscle symptoms (SAMS), have impacted their widespread utilization. In this study, we aimed to develop a predictive model for statin efficacy and safety based on real-world clinical data using machine learning techniques.MethodsWe employed various data preprocessing techniques, such as improved random forest imputation and Borderline SMOTE oversampling, to handle the dataset. Boruta method was utilized for feature selection, and the dataset was divided into training and testing sets in a 7:3 ratio. Five algorithms, including logistic regression, naive Bayes, decision tree, random forest, and gradient boosting decision tree, were used to construct the predictive models. Ten-fold cross-validation and bootstrapping sampling were performed for internal and external validation. Additionally, SHAP (SHapley Additive exPlanations) was employed for feature interpretability. Ultimately, an accessible web-based platform for predicting statin efficacy and safety was established based on the optimal predictive model.ResultsThe random forest algorithm exhibited the best performance among the five algorithms. The predictive models for LDL-C target attainment (AUC = 0.883, Accuracy = 0.868, Precision = 0.858, Recall = 0.863, F1 = 0.860, AUPRC = 0.906, MCC = 0.761), liver enzyme abnormalities (AUC = 0.964, Accuracy = 0.964, Precision = 0.967, Recall = 0.963, F1 = 0.965, AUPRC = 0.978, MCC = 0.938), and muscle pain/Creatine kinase (CK) abnormalities (AUC = 0.981, Accuracy = 0.980, Precision = 0.987, Recall = 0.975, F1 = 0.981, AUPRC = 0.987, MCC = 0.965) demonstrated favorable performance. The most important features of LDL-C target attainment prediction model was cerebral infarction, TG, PLT and HDL. The most important features of liver enzyme abnormalities model was CRP, CK and number of oral medications. Similarly, AST, ALT, PLT and number of oral medications were found to be important features for muscle pain/CK abnormalities. Based on the best-performing predictive model, a user-friendly web application was designed and implemented.ConclusionThis study presented a machine learning-based predictive model for statin efficacy and safety. The platform developed can assist in guiding statin therapy decisions and optimizing treatment strategies. Further research and application of the model are warranted to improve the utilization of statin therapy.
| S-EPMC11317424 | biostudies-literature
Project description:Statin-based treatments reduce cardiovascular disease (CVD) risk in patients with non-dialysis chronic kidney disease (CKD), but it is unclear which regimen is the most cost-effective. We used the Study of Heart and Renal Protection (SHARP) CKD-CVD policy model to evaluate the effect of statins and ezetimibe on quality-adjusted life years (QALYs) and health care costs in the United States (US) and the United Kingdom (UK). Net costs below $100,000/QALY (US) or £20,000/QALY (UK) were considered cost-effective. We investigated statin regimens with or without ezetimibe 10 mg. Treatment effects on cardiovascular risk were estimated per 1-mmol/L reduction in low-density lipoprotein (LDL) cholesterol as reported in the Cholesterol Treatment Trialists' Collaboration meta-analysis, and reductions in LDL cholesterol were estimated for each statin/ezetimibe regimen. In the US, atorvastatin 40 mg ($0.103/day as of January 2019) increased life expectancy by 0.23 to 0.31 QALYs in non-dialysis patients with stages 3B to 5 CKD, at a net cost of $20,300 to $78,200/QALY. Adding ezetimibe 10 mg ($0.203/day) increased life expectancy by an additional 0.05 to 0.07 QALYs, at a net cost of $43,600 to $91,500/QALY. The cost-effectiveness findings and policy implications in the UK were similar. In summary, in patients with non-dialysis-dependent CKD, the evidence suggests that statin/ezetimibe combination therapy is a cost-effective treatment to reduce the risk of CVD.
| S-EPMC6595178 | biostudies-literature
Project description:Aim: To summarize the evidence in terms of efficacy and safety of head-to-head studies of high-intensity statins regardless of the underlying population. Materials & methods: A systematic review and meta-analysis was conducted to summarize the effect sizes in randomized controlled trials and cohort studies that compared high-intensity statins. Results: Based on 44 articles, similar effectiveness was observed across the statins in reducing LDL levels from baseline. All statins were observed to have similar adverse drug reactions (ADRs), although higher dosages were associated with more ADRs. Based on a pooled quantitative analysis of atorvastatin 80 mg versus rosuvastatin 40 mg, rosuvastatin was statistically more effective in reducing LDL. Conclusion: This review further confirms that high-intensity statins reduce LDL by ≥50%, favoring rosuvastatin over atorvastatin. Additional data are needed to confirm the clinical significance on cardiovascular outcomes using real-world studies.
| S-EPMC10288954 | biostudies-literature
Project description:AimWe compared the efficacy and safety of pitavastatin/ezetimibe fixed-dose combination with those of pitavastatin monotherapy in patients with hypercholesterolemia.MethodsThis trial was a multicenter, randomized, double-blind, active-controlled, parallel-group trial. A total of 293 patients were randomly assigned into four groups receiving 2 mg pitavastatin, 4 mg pitavastatin, 2 mg pitavastatin/10 mg ezetimibe (K-924 LD), and 4 mg pitavastatin/10 mg ezetimibe (K-924 HD) once daily for 12 weeks.ResultsThe percentage changes in low-density lipoprotein cholesterol (LDL-C), the primary endpoint, were -39.5% for 2 mg pitavastatin, -45.2% for 4 mg pitavastatin, -51.4% for K-924 LD, and -57.8% for K-924 HD. Compared with pitavastatin monotherapy, the pitavastatin/ezetimibe fixed-dose combination significantly reduced LDL-C, total cholesterol, and non-high-density lipoprotein cholesterol. Meanwhile, the cholesterol synthesis marker, lathosterol, was significantly decreased with pitavastatin monotherapy and the pitavastatin/ezetimibe fixed-dose combination, although the decrease was attenuated in the latter. On the other hand, the cholesterol absorption markers, beta-sitosterol and campesterol, were reduced with the fixed-dose combination but not with pitavastatin monotherapy. The incidence of adverse events and adverse drug reactions was not significantly different between the two groups receiving the fixed-dose combination and monotherapy. The mean values of laboratory tests that are related to liver function and myopathy increased but remained within the reference range in all groups.ConclusionsThe pitavastatin/ezetimibe fixed-dose combination showed an excellent LDL-C-reducing effect by the complementary pharmacological action of each component, and its safety profile was similar to that of pitavastatin monotherapy (ClinicalTrials.gov Identifier: NCT04289649).
| S-EPMC10627746 | biostudies-literature