Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon.
Section of Cardiovascular Medicine, Center for Preventive Cardiology, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA.
Curr Opin Cardiol. 2019 Sep;34(5):519-525. doi: 10.1097/HCO.0000000000000657.
The use of therapeutic monoclonal antibodies to target proprotein convertase subtilisin/kexin type 9 (PCSK9) represents a novel approach to the management of hypercholesteremia and prevention of atherosclerotic cardiovascular disease. We review the most recent literature relevant to PCSK9 inhibition with emphasis on how recent results and ongoing trials have and will continue to shape the use of this new therapeutic class in preventive cardiology.
PCSK9 inhibitors reduce plasma lipoprotein(a) concentrations but a mechanistic understanding remains elusive. Evaluation of evolocumab for use in patients without prior myocardial infarction or stroke is underway (NCT03872401). Concerns regarding the cost-effectiveness of PCSK9 inhibitors have continued to thwart access to these drugs, though innovative models of care delivery and price reductions have improved this situation. Inclisiran, a small interfering ribonucleic acid (siRNA), reduces translation of PCSK9 and demonstrates more durable reductions in low-density lipoprotein-cholesterol (LDL-C). It is currently evaluated in the context of a phase III cardiovascular outcome trial in patients with established vascular disease (NCT03705234).
The current scope of PCSK9 inhibitor therapy in preventive cardiology is limited to patients with familial hypercholesterolemia and/or established atherosclerotic cardiovascular disease. Future cardiovascular outcome trial results with PCSK9 blocking antibodies in primary prevention and with siRNA to PCSK9 in secondary prevention, improved understanding of the drivers of lipoprotein(a) reduction with PCSK9 inhibition, and cost-effectiveness will determine the future role of this therapeutic class.
靶向前蛋白转化酶枯草溶菌素/胰凝乳蛋白酶 9（PCSK9）的治疗性单克隆抗体的使用代表了一种治疗高胆固醇血症和预防动脉粥样硬化性心血管疾病的新方法。我们回顾了与 PCSK9 抑制相关的最新文献，重点介绍了最近的结果和正在进行的试验如何以及将继续塑造这种新治疗类别的在预防心脏病学中的应用。
PCSK9 抑制剂可降低血浆脂蛋白（a）浓度，但对其作用机制仍知之甚少。正在评估依洛尤单抗在无心肌梗死或中风病史的患者中的应用（NCT03872401）。对 PCSK9 抑制剂的成本效益的担忧继续阻碍这些药物的使用，尽管创新的护理提供模式和价格降低改善了这种情况。小干扰核糖核酸（siRNA）依洛西仑可降低 PCSK9 的翻译，并可更持久地降低低密度脂蛋白胆固醇（LDL-C）。目前正在对患有已确诊血管疾病的患者进行 III 期心血管结局试验（NCT03705234）。
目前，PCSK9 抑制剂治疗在预防心脏病学中的应用仅限于家族性高胆固醇血症和/或已确诊的动脉粥样硬化性心血管疾病患者。在一级预防中使用 PCSK9 阻断抗体和在二级预防中使用 siRNA 治疗 PCSK9 的未来心血管结局试验结果、对 PCSK9 抑制降低脂蛋白（a）的驱动因素的更深入了解以及成本效益将决定这种治疗类别的未来作用。
