Imperial Centre for Cardiovascular Disease Prevention, School of Public Health, Imperial College London, London, UK.
Pharmacology Department, School of Medicine, FASTA University, Mar del Plata, Argentina.
Lancet. 2019 Aug 24;394(10199):697-708. doi: 10.1016/S0140-6736(19)31950-6.
Atherosclerosis and its clinical manifestation as ischaemic heart disease remains a considerable health burden. Given that many factors contribute to ischaemic heart disease, a multifactorial approach to prevention is recommended, starting with lifestyle advice, smoking cessation, and control of known cardiovascular risk factors, such as blood pressure and lipids. Within the lipid profile, the principal target is lowering LDL cholesterol, firstly with lifestyle interventions and subsequently with pharmacological therapy. Statins are the recommended first-line pharmacological treatment. Some individuals might require further lowering of LDL cholesterol or be unable to tolerate statins. Additional therapies targeting different pathways in cholesterol metabolism are now available, ranging from small molecules taken orally, to injectable therapies. Examples include ezetimibe, which targets Niemann-Pick C1-like protein, and monoclonal antibodies that target PCSK9. Phase 3 trials have also been completed for bempedoic acid (targeting ATP-citrate lyase) and inclisiran (an interference RNA-based therapeutic targeting hepatic PCSK9 synthesis). In addition to LDL cholesterol, mendelian randomisation studies support a causal role for lipoprotein(a) and triglycerides in ischaemic heart disease. In this Series paper, we appraise currently available and emerging therapies for lowering LDL cholesterol, lipoprotein(a), and triglycerides for prevention of ischaemic heart disease.
动脉粥样硬化及其临床表现如缺血性心脏病仍然是一个相当大的健康负担。鉴于许多因素导致缺血性心脏病，建议采取多因素预防方法，首先从生活方式建议、戒烟和控制已知的心血管危险因素（如血压和血脂）开始。在血脂谱中，主要目标是降低 LDL 胆固醇，首先通过生活方式干预，然后通过药物治疗。他汀类药物是推荐的一线药物治疗。有些人可能需要进一步降低 LDL 胆固醇，或者不能耐受他汀类药物。现在有针对胆固醇代谢不同途径的额外治疗方法，包括口服小分子药物和注射治疗药物。例如，依折麦布靶向 Niemann-Pick C1 样蛋白，单克隆抗体靶向 PCSK9。贝美前列素（靶向 ATP-柠檬酸裂解酶）和inclisiran（一种基于干扰 RNA 的针对肝脏 PCSK9 合成的治疗药物）的 3 期临床试验也已完成。除了 LDL 胆固醇外，孟德尔随机化研究支持脂蛋白(a)和甘油三酯在缺血性心脏病中的因果作用。在本系列论文中，我们评估了目前可用于降低 LDL 胆固醇、脂蛋白(a)和甘油三酯以预防缺血性心脏病的治疗方法。
