维曲西泮对转甲状腺素蛋白淀粉样变心肌病患者心脏结构和功能的影响：HELIOS-B试验的次要结果

Effects of vutrisiran on cardiac structure and function in patients with transthyretin amyloidosis with cardiomyopathy: secondary outcomes of the HELIOS-B trial.

作者信息

Jering Karola S, Fontana Marianna, Lairez Olivier, Longhi Simone, Azevedo Olga, Morbach Caroline, Bender Shaun, Jay Patrick Y, Vest John, Bulwer Bernard E, Prasad Narayana, Solomon Scott D, Skali Hicham

机构信息

Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.

National Amyloidosis Centre, Division of Medicine, University College London, Royal Free Hospital, London, UK.

出版信息

Nat Med. 2025 Aug 6. doi: 10.1038/s41591-025-03851-z.

DOI:10.1038/s41591-025-03851-z

PMID:40770082

Abstract

In the HELIOS-B randomized clinical trial, the RNA interference therapeutic agent vutrisiran reduced the risk of all-cause mortality and recurrent cardiovascular events among patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). In this secondary analysis of HELIOS-B, we evaluated vutrisiran's effects on echocardiographic measures of cardiac structure and function in patients with ATTR-CM receiving vutrisiran or placebo (n = 654, 93% men). At 30 months after treatment, as compared to the placebo group, vutrisiran treatment attenuated increases in mean left ventricular (LV) wall thickness (least squares mean difference: -0.4 mm; 95% confidence interval (CI): -0.8, 0.0; P = 0.03) and LV mass index (-10.6 g m; 95% CI: -18.0, -3.3; P < 0.01). Vutrisiran treatment also attenuated declines in LV ejection fraction (2.0%; 95% CI: 0.3, 3.7; P = 0.02), absolute global longitudinal strain (1.2%; 95% CI: 0.7, 1.7; P < 0.01) and LV stroke volume (4.1 ml; 95% CI: 1.7, 6.4; P < 0.01), and decreased both the average ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity (-2.0; 95% CI: -2.9, -1.2; P < 0.01) and the early to late diastolic transmitral flow velocities ratio (-0.3; 95% CI: -0.6, -0.0; P = 0.04), as compared to placebo. Consistent with its clinical benefits, these echocardiographic findings indicate favorable effects of vutrisiran on cardiac structure and function in patients with ATTR-CM. ClinicalTrials.gov registration: NCT04153149 .

摘要

在HELIOS-B随机临床试验中，RNA干扰治疗药物vutrisiran降低了转甲状腺素蛋白淀粉样变心肌病（ATTR-CM）患者的全因死亡率和心血管事件复发风险。在对HELIOS-B的这项二次分析中，我们评估了vutrisiran对接受vutrisiran或安慰剂治疗的ATTR-CM患者心脏结构和功能的超声心动图测量指标的影响（n = 654，93%为男性）。治疗30个月后，与安慰剂组相比，vutrisiran治疗减弱了平均左心室（LV）壁厚度的增加（最小二乘均值差异：-0.4毫米；95%置信区间（CI）：-0.8，0.0；P = 0.03）和LV质量指数（-10.6克/平方米；95% CI：-18.0，-3.3；P < 0.01）。vutrisiran治疗还减弱了LV射血分数的下降（2.0%；95% CI：0.3，3.7；P = 0.02）、绝对整体纵向应变（1.2%；95% CI：0.7，1.7；P < 0.01）和LV每搏输出量（4.1毫升；95% CI：1.7，6.4；P < 0.01），并且与安慰剂相比，降低了舒张早期二尖瓣血流速度与舒张早期二尖瓣环组织速度的平均比值（-2.0；95% CI：-2.9，-1.2；P < 0.01）以及舒张早期与晚期二尖瓣血流速度比值（-0.3；95% CI：-0.6，-0.0；P = 0.04）。与其临床益处一致，这些超声心动图结果表明vutrisiran对ATTR-CM患者的心脏结构和功能有有利影响。ClinicalTrials.gov注册号：NCT04153149 。