Division of Cardiology and.
CPC Clinical Research, Aurora, Colorado 80045.
Annu Rev Med. 2018 Jan 29;69:133-145. doi: 10.1146/annurev-med-042716-091351. Epub 2017 Nov 2.
Atherosclerotic cardiovascular disease (ASCVD) is associated with significant morbidity and mortality worldwide. Increased serum levels of low-density lipoprotein cholesterol (LDL-C) are an independent risk factor for ASCVD, and clinical trial data have shown that lowering LDL-C generally reduces cardiovascular risk. Until recently, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been the main therapy for lowering LDL-C. However, some statin-treated patients have persistently elevated residual cardiovascular risk due to inadequate lowering of LDL-C levels or non-LDL-related dyslipidemia. In addition, adverse effects of statins may limit their tolerability and therefore the ability to attain effective doses in some patients. A new class of drugs that inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) has been developed to treat hyperlipidemia. This review discusses the history and mechanism of action of PCSK9 inhibitors, their metabolic effects, and clinical outcomes associated with these medications, highlighting recent large cardiovascular outcome trials investigating these therapies.
动脉粥样硬化性心血管疾病（ASCVD）在全球范围内与较高的发病率和死亡率相关。血清中低密度脂蛋白胆固醇（LDL-C）水平升高是 ASCVD 的一个独立危险因素，临床试验数据表明降低 LDL-C 通常可降低心血管风险。直到最近，3-羟基-3-甲基戊二酰辅酶 A（HMG-CoA）还原酶抑制剂（他汀类药物）一直是降低 LDL-C 的主要治疗方法。然而，由于 LDL-C 水平降低不足或非 LDL 相关血脂异常，一些接受他汀类药物治疗的患者仍存在持续升高的残余心血管风险。此外，他汀类药物的不良反应可能限制其耐受性，从而限制了某些患者达到有效剂量的能力。现已开发出一类新型抑制前蛋白转化酶枯草溶菌素 9（PCSK9）的药物来治疗高脂血症。本文讨论了 PCSK9 抑制剂的历史和作用机制、它们的代谢作用以及与这些药物相关的临床结局，重点介绍了最近调查这些治疗方法的大型心血管结局试验。
