Ogunniyi Kayode, Aghasili Chukwuemeka Christian, Akinmoju Olumide, Olaiya Victor Olamiposi, Abib Oluwamisimi, Odueke Adetayo Y, Popoola Hakeem Adegboyega, Onyenokwe Victor, Onaolapo David, Usman Abdul-Azeez Muhammed, Friedman Adam, Awoyemi Toluwalase, Nfonoyim Jay, Rotatori Francesco
Richmond University Medical Center/Mount Sinai, Staten Island, NY, USA.
Royal College of Physicians, London, UK.
Am J Cardiovasc Drugs. 2025 Aug 30. doi: 10.1007/s40256-025-00762-9.
Despite the well-established benefits of statin therapy in reducing atherosclerotic cardiovascular disease (ASCVD) risk, many patients fail to achieve recommended low-density lipoprotein cholesterol (LDL-C) targets or experience statin intolerance, necessitating alternative approaches. This review examines advances in non-statin lipid-lowering therapies, focusing on proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (monoclonal antibodies and inclisiran), bempedoic acid, and other non-statin lipid medications. We evaluate their mechanisms of action, clinical efficacy, and safety profiles on the basis of landmark trials. A conceptual framework for personalized lipid management is proposed, addressing residual cardiovascular risk, statin intolerance, and complex patient profiles. Clinical decision pathways are presented for high-risk patients, statin-intolerant individuals, and those with adherence challenges. We explore emerging therapies targeting novel pathways, including lipoprotein(a), apolipoprotein C-III inhibitors, angiopoietin-like protein 3 (ANGPTL3) inhibitors, cholesteryl ester transfer protein (CETP) inhibitors, and gene-editing technologies. Implementation barriers, including cost considerations, insurance challenges, and global access disparities, are discussed alongside solutions.
尽管他汀类药物治疗在降低动脉粥样硬化性心血管疾病（ASCVD）风险方面具有公认的益处，但许多患者未能达到推荐的低密度脂蛋白胆固醇（LDL-C）目标，或出现他汀类药物不耐受，因此需要采用替代方法。本综述探讨了非他汀类降脂疗法的进展，重点关注前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）抑制剂（单克隆抗体和inclisiran）、贝派地酸和其他非他汀类降脂药物。我们根据标志性试验评估它们的作用机制、临床疗效和安全性。提出了个性化血脂管理的概念框架，以解决残留心血管风险、他汀类药物不耐受和复杂的患者情况。为高危患者、他汀类药物不耐受个体以及那些存在依从性挑战的患者提供了临床决策路径。我们探索针对新途径的新兴疗法，包括脂蛋白（a）、载脂蛋白C-III抑制剂、血管生成素样蛋白3（ANGPTL3）抑制剂、胆固醇酯转运蛋白（CETP）抑制剂和基因编辑技术。同时讨论了实施障碍，包括成本考虑、保险挑战和全球可及性差异以及解决方案。
