Xia Jiachun, Wang Xinyue, Zhou Jun, Wang Dong, Pang Yanan, Xu Xin, Sang Zhenchi, Zhang Yi, Zhang Junfeng, Wu Sicheng, Xiao Zhengguang, Hou Lei
Institute of Cardiovascular Diseases, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Cardiovasc Med. 2022 Sep 23;9:1009674. doi: 10.3389/fcvm.2022.1009674. eCollection 2022.
Primary percutaneous coronary intervention (PPCI) is the most effective treatment strategy for ST-segment elevation myocardial infarction (STEMI). Nevertheless, dysregulated inflammation induced by myocardial reperfusion injury may increase the final infarct size and induce maladaptive myocardial remodeling. Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor, as a novel and potent lipid-lowering drug, plays an important role in inflammation. The aim of this study is to investigate whether the early application of PCSK9 inhibitor can increase the myocardial salvage index (MSI) and improve ventricular remodeling in patients with STEMI.
The PERFECT II trial is a prospective, open-label, multicenter, randomized controlled study involving 160 patients with STEMI who are scheduled to undergo PPCI. The eligible patients will be divided into PCSK9 inhibitor group and control group the interactive web response system, at a 1:1 ratio. In the PCSK9 inhibitor group, the PCSK9 inhibitor alirocumab at a dose of 75 mg will be subcutaneously injected immediately after PPCI and administered every 2 weeks thereafter for 3 months based on conventional treatment. In the control group, conventional treatment will be administered. The primary endpoint is MSI, as measured by cardiac magnetic resonance imaging (CMR) at 1 week after PPCI. The secondary endpoints are the peak time of creatine kinase (CK)-MB and troponin I (TnI)/TnT after PPCI; the postoperative fall time of the ST segment on electrocardiography (ECG); the rate of plasma low-density lipoprotein cholesterol (LDL-C) compliance (< 1.4 mmol/L and a reduction of >50% from baseline) at 1, 3, and 6 months after PPCI; infarct size and ejection fraction (EF) measured by CMR at 6 months after PPCI; the occurrence of major adverse cardiovascular event (MACE: a composite of cardiovascular death, non-fatal myocardial infarction, stent thrombosis, repeat revascularization, stroke, and heart failure needed to be hospitalized).
This is the first multicenter study to investigate the effect of early application of the PCSK9 inhibitor alirocumab on MSI in patients with STEMI undergoing PPCI. The findings will provide an opportunity to explore novel ideas and methods for the treatment of acute myocardial infarction.
ClinicalTrials.gov, identifier: NCT05292404.
直接经皮冠状动脉介入治疗（PPCI）是ST段抬高型心肌梗死（STEMI）最有效的治疗策略。然而，心肌再灌注损伤引起的炎症调节异常可能会增加最终梗死面积并导致适应性不良的心肌重塑。前蛋白转化酶枯草溶菌素/克新9（PCSK9）抑制剂作为一种新型强效降脂药物，在炎症中起重要作用。本研究的目的是探讨早期应用PCSK9抑制剂是否能提高STEMI患者的心肌挽救指数（MSI）并改善心室重塑。
PERFECT II试验是一项前瞻性、开放标签、多中心、随机对照研究，纳入160例计划接受PPCI的STEMI患者。符合条件的患者将通过交互式网络响应系统以1:1的比例分为PCSK9抑制剂组和对照组。在PCSK9抑制剂组中，75 mg剂量的PCSK9抑制剂阿利西尤单抗将在PPCI后立即皮下注射，此后每2周给药一次，共3个月，并基于常规治疗。对照组将给予常规治疗。主要终点是MSI，在PPCI后1周通过心脏磁共振成像（CMR）测量。次要终点是PPCI后肌酸激酶（CK）-MB和肌钙蛋白I（TnI）/TnT的峰值时间；心电图（ECG）上ST段的术后下降时间；PPCI后1、3和6个月时血浆低密度脂蛋白胆固醇（LDL-C）达标率（<1.4 mmol/L且较基线降低>50%）；PPCI后6个月通过CMR测量的梗死面积和射血分数（EF）；主要不良心血管事件（MACE：心血管死亡、非致命性心肌梗死、支架血栓形成、再次血管重建、中风和需住院治疗的心力衰竭的复合事件）的发生情况。
这是第一项研究早期应用PCSK9抑制剂阿利西尤单抗对接受PPCI的STEMI患者MSI影响的多中心研究。研究结果将为探索急性心肌梗死的新治疗思路和方法提供契机。
ClinicalTrials.gov，标识符：NCT05292404。
