CBS - The 17th Left Main & Coronary Bifurcation Summit, CBS2025

HOME | SCIENTIFIC LIBRARY | DAPT Duration

DAPT Duration

Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCIThe STOPDAPT-2 Randomized Clinical Trial DAPT, Our Genome and Clopidogrel 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery Characterization of the Average Daily Ischemic and Bleeding Risk After Primary PCI for STEMI Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial Patterns and associations between DAPT cessation and 2-year clinical outcomes in left main/proximal LAD versus other PCI: Results from the Patterns of Non-Adherence to Dual Antiplatelet Therapy in Stented Patients (PARIS) Reduced risk of gastrointestinal bleeding associated with proton pump inhibitor therapy in patients treated with dual antiplatelet therapy after myocardial infarction

Sort by hits |<< 1 2 3 4 5 6 7 ...>>|

Original Research

JOURNAL：CBSMD Article Link

PCSK9 抑制剂的今生未来

CBSMD

Pre-reading

胆固醇假说的核心观点，即血浆高胆固醇是动脉粥样硬化性心血管疾病的主要致病因素，降低胆固醇可以降低心血管疾病事件。PCSK9（前蛋白转化酶枯草溶菌素9）于2003年经首次报道，PCSK9主要的生理作用是介导肝细胞低密度脂蛋白受体(low density lipoprotein receptor，LDLR)降解，减少LDLR对血浆低密度脂蛋白胆固醇(LDL-cholesterol，LDL-C)的摄取，在LDL-C代谢中扮演关键角色。然而，PCSK9基因突变患者的高胆固醇血症更严重，且使用他汀类难以治疗; PCSK9基因错义突变（missense mutation）导致的功能增加（gain-of-function）会引起常染色体显性高胆固醇血症; PCSK9无义突变（nonsense mutation)导致的功能丧失（loss-of-function）可导致血浆LDL-C降低幅度高达40%。

“Sequence variations in PCSK9, low LDL, and protection against coronary heart disease”于2006年发现PCSK9无义突变杂合携带者的LDL-C水平与非携带者的相比降低了28%，冠状动脉疾病（心梗、致死性冠心病或冠状动脉重建）降低了80%，开启了PCSK9作为心血管患者降脂靶向基因的新纪元。

近日发表的“Cholesterol-Lowering Agents”全面系统地剖析PCSK9的各个层面：
1. 说明了PCSK9主要在肝脏中调节低密度脂蛋白的作用机制；
2. 介绍了PCSK9在此之外与动脉粥样硬化病变及与可导致粥样硬化炎性之间的反应机制（详见图一）；
3. 梳理了现今所有有关PCSK9抑制剂相关的临床研究及进展（详见表一）；
4. 以及PCSK9抑制剂降低血管事件的成效。

PCSK9抑制剂依伏库单抗（Evolocumab）

最新发表的"Effect of the PCSK9 Inhibitor Evolocumab on Total Cardiovascular Events in Patients With Cardiovascular DiseaseA Prespecified Analysis From the FOURIER Trial"进一步报道了依伏库单抗（Evolocumab）对动脉粥样硬化患者中期罹患主要临床终点事件总人次的削弱作用，主要预防作用是通过降低心梗、卒中和血运重建发生率而实现的。

现有CBSMD Scientific Library收录的“Evolocumab”与临床事件相关的研究文献可参阅：
“Mortality Differences Associated With Treatment Responses in CANTOS and FOURIER: Insights and Implications”

“Clinical Efficacy and Safety of Evolocumab in High-Risk Patients Receiving a Statin: Secondary Analysis of Patients With Low LDL Cholesterol Levels and in Those Already Receiving a Maximal-Potency Statin in a Randomized Clinical Trial”

“Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease”

PCSK9抑制剂阿利库单抗(alirocumab)

2018年10月ODYSSEY研究首项证实最大耐受剂量他汀（statins）基础上联合PCSK9抑制剂阿利库单抗(alirocumab)治疗改善ACS患者的预后。ODYSSEY OUTCOMES研究结果显示每2周服用阿利库单抗可有效降低既往1-12个月内发生ACS事件患者未来缺血性事件，包括全因死亡和心梗。试验设计为在经最大耐受剂量他汀治疗后低密度脂蛋白胆固醇（LDL-C）水平仍未达标的患者中加入阿利库单抗，观察其相较于安慰剂对主要心血管事件的降幅，其中LDL-C≥100 mg/dl的ACS患者获益最大。

2019年4月26日FDA（The U.S. Food and Drug Administration）更新了阿利库单抗的药物说明书：

- 可作为降低成年心血管疾病患者发生心肌梗死、卒中和需要住院治疗的不稳定心绞痛的风险的二级预防药物；
- 可作为配合节食、单独或联合其他降脂疗法(如他汀类药物、依扎替米布)治疗成人原发性高脂血症(包括杂合子家族性高胆固醇血症)，以降低低密度脂蛋白胆固醇LDL-C的药物。

Abstract

Recommended Article

PCSK9 抑制剂的今生未来

Pre-reading