Search strategy for PubMed.

IntroductionHyperlipidemia is increasingly recognized as a significant global health issue, often associated with conditions such as hypertension, diabetes, and obesity. While statins are frequently prescribed to manage lipid levels, recent studies indicate that reliance solely on statin therapy may present certain disadvantages, including prolonged treatment durations, the potential for drug resistance, and various adverse effects. Research indicates that the combination of ezetimibe and statins demonstrates a favorable therapeutic effect in the management of hyperlipidemia. However, existing studies have not consistently confirmed these benefits, and there is no current meta-analysis available. As a result, we will perform a meta-analysis to assess the effectiveness and safety of the combination of ezetimibe and statins in managing hyperlipidemia, aiming to offer evidence-based medical guidance for clinical practice.Methods and analysisThe systematic review and meta-analysis will adhere to the PRISMA guidelines for systematic reviews and meta-analyses. We will search for randomized controlled trials that investigate the efficacy and safety of the combination of ezetimibe and statins in treating hyperlipidemia, based on specific criteria. The following electronic databases will be searched by two researchers for relevant records published up to October 1, 2024: Cochrane Central Register of Controlled Trials (CENTRAL) in Cochrane Library, Embase.com, Web of Science, MEDLINE (via PubMed), Wanfang China Database, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM) and Chinese Scientific Journal Database (VIP). They will also check references and relevant journals manually. Two independent reviewers will handle screening, data extraction, and quality assessment. Subgroup analysis, sensitivity analysis, and publication bias analysis will be performed to assess consistency and reliability. Review Manager 5.4 will be used for data analysis and synthesis, while the GRADE approach will be employed to evaluate the overall study’s evidence quality.Expected resultsThe findings of this systematic review will be shared with various stakeholders who are interested in the combination of ezetimibe and statins for hyperlipidemia. This will offer valuable insights for researchers undertaking future investigations and for clinical practitioners specializing in the treatment of hyperlipidemia.Ethics and disseminationThis study is based on a secondary analysis of the literature, so ethical review approval is not required. The final report will be published in a peer-reviewed journal.Study registrationThe protocol of the systematic review has been registered on Open Science Framework, with a registration DOI https://doi.org/10.17605/OSF.IO/TEVUY.

引言
高脂血症（Hyperlipidemia）日益被视为一项重要的全球公共卫生问题，常与高血压、糖尿病、肥胖等病症相关联。尽管他汀类药物（statins）常被用于调控血脂水平，但近期研究显示，单纯依赖他汀类药物治疗可能存在若干弊端，包括治疗周期延长、产生耐药性的风险以及多种不良反应。研究表明，依折麦布（ezetimibe）与他汀类药物联合使用在高脂血症管理中展现出良好的治疗效果。然而，现有研究尚未能一致证实此类获益，且目前尚无相关荟萃分析（meta-analysis）问世。有鉴于此，本研究拟开展一项荟萃分析，以评估依折麦布与他汀类药物联合治疗高脂血症的有效性与安全性，旨在为临床实践提供循证医学指导。

方法与分析
本系统评价与荟萃分析将遵循《系统评价和荟萃分析优先报告条目》（PRISMA）规范。我们将依据特定纳入排除标准，检索探讨依折麦布与他汀类药物联合治疗高脂血症的有效性与安全性的随机对照试验（randomized controlled trial, RCT）。两名研究者将检索截至2024年10月1日发表的相关文献，检索数据库包括：Cochrane图书馆的Cochrane对照试验中心注册库（Cochrane Central Register of Controlled Trials, CENTRAL）、Embase.com、Web of Science、MEDLINE（通过PubMed检索）、万方数据知识服务平台（Wanfang China Database）、中国知网（China National Knowledge Infrastructure, CNKI）、中国生物医学文献数据库（Chinese Biomedical Literature Database, CBM）以及中文科技期刊数据库（Chinese Scientific Journal Database, VIP）。同时，研究者还将手动检索参考文献列表及相关期刊。由两名独立的研究者分别负责文献筛选、数据提取与质量评价。本研究将开展亚组分析、敏感性分析与发表偏倚分析，以评估结果的一致性与可靠性。将采用Review Manager 5.4软件进行数据分析与合成，并采用推荐分级的评估、制订与评价（GRADE）方法评估本研究的整体证据质量。

预期结果
本系统评价的研究结果将分享给所有关注依折麦布与他汀类药物联合治疗高脂血症的相关方，可为未来开展相关研究的学者以及专注于高脂血症诊疗的临床医师提供有价值的参考依据。

伦理与传播
本研究为文献二次分析，无需获得伦理审查批准。最终研究报告将发表于经同行评议的期刊。

研究注册
本系统评价的研究方案已在开放科学框架（Open Science Framework）注册，注册DOI为https://doi.org/10.17605/OSF.IO/TEVUY。