Iannuzzo Gabriella, Kamboj Geetank, Barman Parinita, Dongare Shirish, Jawla Shantanu
Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Skyward Analytics Pvt. Ltd., Gurugram, India.
Atheroscler Plus. 2024 Oct 17;58:24-37. doi: 10.1016/j.athplu.2024.10.001. eCollection 2024 Dec.
Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk.
EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs.
The search strategy yielded 2104 citations. Post screening for eligibility, nine unique trials/studies (84 publications) were identified. Among these, one trial each was identified for bempedoic acid and alirocumab, three for evolocumab, and four for ezetimibe. No published literature documenting the cardiovascular outcomes of inclisiran was identified. Only one trial (CLEAR Outcomes) included statin-intolerant patients at baseline. Most studies evaluated a 3-component, 4-component, or 5-component major adverse cardiovascular events composite as an outcome along with individual components. The quality of the included trials was found to be fair-to-good.
The systematic review findings emphasise the significance of considering non-statin LLTs as viable treatment options for individuals with CVD or high cardiovascular risk who cannot tolerate or achieve optimal lipid control with statin therapy alone.
心血管疾病（CVD）给全球健康带来了重大负担。降低低密度脂蛋白胆固醇是预防原发性和继发性心血管疾病事件的主要治疗目标。虽然他汀类药物是标准治疗方法，但它们存在局限性，如某些患者群体的副作用和不耐受性，因此有必要探索替代的降脂疗法（LLT）。我们系统回顾了评估非他汀类LLT（贝派地酸、阿利西尤单抗、依洛尤单抗、依折麦布和英克西兰）与患有心血管疾病或心血管风险高的成年人的心血管结局相关的随机对照试验（RCT）。
从数据库建立至2023年2月8日，系统检索了EMBASE、Medline、Cochrane图书馆和临床试验注册库中的 eligible 研究。两名评审员独立筛选研究，如有分歧由第三名评审员解决。进行了数据提取和验证，并使用Cochrane偏倚风险工具-2对RCT进行偏倚风险评估。
检索策略产生了2104条引文。在筛选 eligible 性后，确定了9项独特的试验/研究（84篇出版物）。其中，贝派地酸和阿利西尤单抗各有1项试验，依洛尤单抗有3项试验，依折麦布有4项试验。未找到记录英克西兰心血管结局的已发表文献。只有1项试验（CLEAR Outcomes）在基线时纳入了他汀类药物不耐受的患者。大多数研究评估了3组分、4组分或5组分的主要不良心血管事件复合结局以及各个组分。发现纳入试验的质量为中等至良好。
系统评价结果强调，对于不能耐受他汀类药物治疗或仅用他汀类药物治疗无法实现最佳血脂控制的心血管疾病患者或心血管风险高的个体，将非他汀类LLT视为可行的治疗选择具有重要意义。
