The Cardiac Center of Creighton University, Omaha, NE 68131, USA.
Postgrad Med. 2012 Nov;124(6):43-54. doi: 10.3810/pgm.2012.11.2612.
This article reviews the current status of lipid-lowering drugs and their impact on cardiovascular morbidity and mortality. Because there is compelling evidence to suggest that substantial residual risk persists despite the use of current lipid-lowering treatments, novel strategies for managing dyslipidemia are discussed.
Statins remain the drugs of choice for the treatment of dyslipidemia in patients with coronary heart disease or substantial risk factors for coronary heart disease. The evidence supporting the use of non-statin monotherapy for reductions in cardiovascular morbidity and mortality is examined. Furthermore, the evidence supporting the use of combinations of lipid-lowering drugs, primarily a statin plus another agent, for reductions in cardiovascular morbidity and mortality is discussed. Available clinical data for novel dyslipidemia drugs that can potentially expand on the current known benefits of statin therapy are reviewed. The cholesteryl ester transfer protein inhibitors, which predominantly increase high-density lipoprotein cholesterol levels and can also substantially lower low-density lipoprotein cholesterol levels, have the most robust clinical trial data, including some phase 3 study results. The proprotein convertase subtilisin/kexin type 9 inhibitors, which predominantly impact low-density lipoprotein cholesterol, are also being tested in phase 3 studies, but their widespread application may be limited by their need to be administered by injection. Peroxisome proliferator-activated receptor (PPAR) agonists with dual agonism of PPAR-α and PPAR-γ to optimize glycemic and lipid profiles may benefit patients with both diabetes and cardiovascular disease. The other novel lipid-lowering drugs are in earlier-phase human testing.
Novel agents have the potential to be valuable additions to current treatment of dyslipidemia to reduce cardiovascular morbidity and mortality. These new drugs will not only have to be able to demonstrate an improvement in patients' lipid profiles, but will also have to be able to demonstrate that they reduce cardiovascular morbidity and mortality, typically in combination with statin therapy.
本文综述了降脂药物的现状及其对心血管发病率和死亡率的影响。由于有强有力的证据表明，尽管使用了目前的降脂治疗方法，仍存在大量的残余风险，因此讨论了管理血脂异常的新策略。
他汀类药物仍然是冠心病或有冠心病高风险因素患者治疗血脂异常的首选药物。本文检查了支持使用非他汀类药物单药治疗降低心血管发病率和死亡率的证据。此外，还讨论了使用降脂药物联合治疗（主要是他汀类药物加另一种药物）降低心血管发病率和死亡率的证据。还回顾了新型血脂异常药物的临床数据，这些药物有可能扩大他汀类药物治疗的现有已知益处。胆固醇酯转移蛋白抑制剂主要增加高密度脂蛋白胆固醇水平，也能显著降低低密度脂蛋白胆固醇水平，具有最丰富的临床试验数据，包括一些 3 期研究结果。前蛋白转化酶枯草溶菌素/ kexin 9 抑制剂主要影响低密度脂蛋白胆固醇，也正在 3 期研究中进行测试，但由于需要注射给药，其广泛应用可能受到限制。具有双重激动剂作用的过氧化物酶体增殖物激活受体（PPAR）激动剂，即 PPAR-α 和 PPAR-γ 的双重激动剂，可优化血糖和血脂谱，可能使同时患有糖尿病和心血管疾病的患者受益。其他新型降脂药物处于早期人体试验阶段。
新型药物有可能成为当前治疗血脂异常以降低心血管发病率和死亡率的有效补充。这些新药不仅要能够改善患者的血脂谱，而且还必须能够证明它们能够降低心血管发病率和死亡率，通常需要与他汀类药物联合治疗。
