Simvastatin 40mg / Ezetimibe 10mg tablets

Background and aimsStatins, ezetimibe and statins-ezetimibe combination therapy are recommended lipid-lowering therapies (LLTs) in children with heterozygous familial hypercholesterolaemia (HeFH). However, their relative effectiveness is not well understood. We aimed to compare the safety and efficacy of these therapies using direct and indirect comparisons.MethodsWe conducted systematic review, pairwise and network meta-analyses (NMAs) of randomised-controlled trials (RCTs) of statins, ezetimibe and statins-ezetimibe combination therapy in people ResultsThirteen RCTs were included (n = 1649, median age 13 years, follow-up 6 weeks-2 years). All LLTs reduced low-density lipoprotein cholesterol (LDL-C) and total cholesterol; statins led to increases in high-density lipoprotein cholesterol and reductions in triglycerides. Statins reduced LDL-C by 33.61 % against placebo (95 % CI 27.58 to 39.63, I2 = 83 %). Adding ezetimibe to statins reduced LDL-C by an additional 15.85 % (95 % CI 11.91 to 19.79). NMAs showed intermediate-dose statins reduced LDL-C by an additional 4.77 % compared with lower-doses statins (95 % CrI -11.22 to 1.05); higher-dose statins and intermediate-dose statins + ezetimibe may be similarly effective and are probably superior to ezetimibe, intermediate-and lower-dose statins. There was no evidence of differences in maturation, safety or tolerability between LLTs and placebo.ConclusionsStatins, ezetimibe and statins-ezetimibe are all effective treatments for children with HeFH, but the magnitude of LDL-C reductions varies and may depend on treatment dosage and combination. No safety or tolerability issues were found. Longer-term safety and effectiveness are uncertain.

Abstract licence: CC BY

As commonly used lipid-lowering drugs, the efficacy and safety of statins, ezetimibe, and fibrates, either alone or in combination, have rarely been systematically evaluated. Therefore, we conducted a network meta-analysis to assess their efficacy and safety in patients with hyperlipidemia. In this study, we searched PubMed, the Cochrane Library, and Web of Science within our system. We included randomized controlled trials (RCTs) that compared the monotherapy or combination therapy of statins, ezetimibe, and fibrates for hyperlipidemia. Data analysis was performed using Stata 17.0 software. Each result is presented as the mean difference (MD) or odds ratio (OR) along with the 95% confidence interval (CI) and the surface under the cumulative ranking curve (SUCRA). A total of 30 studies, involving 10,219 patients, were included to analyze 12 different interventions. Combination therapy demonstrated superior therapeutic effects compared to monotherapy. Moderate-intensity statin + ezetimibe showed good efficacy and acceptable safety in reducing LDL cholesterol, while moderate-intensity statin + fibrate was a better choice for treating mixed dyslipidemia.

Abstract licence: CC BY-NC-ND

Statins represent the first-line therapy for cholesterol management. However, for patients prone to statin side effects, unable to tolerate higher doses, or requiring additional low-density lipoprotein cholesterol (LDL-C) reduction, ezetimibe alone or in combination with statins is recommended. This meta-analysis aimed to evaluate the safety and efficacy of combining low- or moderate-intensity statins with ezetimibe compared to high-intensity statin monotherapy, yielding reliable evidence to guide clinical decision-making and personalize treatment strategies. PubMed, Embase, and Scopus were systematically searched from inception until May 2023. All randomized controlled trials (RCTs) comparing a high-intensity statin with a low/moderate-intensity statin with ezetimibe were included. The outcomes of interest comprised changes in concentrations of lipids-LDL-C, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TGs)-and apolipoprotein (Apo) A1, Apo B, and high-sensitivity C-reactive protein (hs-CRP), along with major adverse cardiovascular events (MACE). All data were analyzed using Review Manager version 5.4. p-values less than 0.05 were considered to indicate statistical significance. Overall, 20 RCTs, with 5,412 participants, were included. A low/moderate-intensity statin combined with ezetimibe yielded a significantly greater reduction in LDL-C levels than high-intensity statin monotherapy (mean difference [MD], -6.59; 95% confidence interval [CI], -10.95, -2.24; p=0.003; I2=84%). No significant differences were observed between combination and high-intensity statin monotherapy regarding TC, TG, or HDL-C levels. However, hs-CRP levels were significantly higher with combination therapy (MD, 0.32; 95% CI, 0.01, 0.64; p=0.04; I2=0%). Combination therapy involving a low/moderate-intensity statin with ezetimibe was significantly associated with lower LDL-C levels than high-intensity statin monotherapy. No significant differences were observed for TC, TGs, HDL-C, alanine transaminase, or MACE. However, creatine phosphokinase levels significantly increased with monotherapy.

Abstract licence: CC BY-NC