Impact of Vutrisiran on Outpatient Worsening Heart Failure in Patients with Transthyretin Amyloidosis with Cardiomyopathy in the HELIOS-B Trial

IF 2.6 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart & Lung Pub Date : 2025-05-30 DOI:10.1016/j.hrtlng.2025.04.012

Cynthia Bither ACNP, ANP, AACC, CHFN, Marianna Fontana MD, PhD, Mathew S. Maurer MD, Scott D. Solomon MD, Julian Gillmore MD, PhD, Shaun Bender PhD, Emre Aldinc MD, Satish Eraly MD, PhD, Patrick Jay MD, PhD

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Abstract

Background

Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a fatal disease, caused by transthyretin amyloid fibril deposits in the heart. Practical and sensitive methods are needed to monitor patients with disease progression and optimize treatment decisions. Outpatient worsening heart failure (HF) (oral diuretic intensification or initiation) has been shown to be prognostic of mortality in patients with ATTR-CM. In the phase 3 HELIOS-B trial (NCT04153149), the RNAi therapeutic vutrisiran reduced the risk of all-cause mortality (ACM) and recurrent CV events (CV hospitalizations and urgent HF visits) vs placebo in patients with ATTR-CM.

Aim

To investigate the clinical and prognostic value of—in addition to the effect of vutrisiran on—outpatient worsening HF in patients with ATTR-CM.

Methods

Associations between outpatient worsening HF and the HELIOS-B primary composite of ACM and recurrent CV events, ACM alone, and other disease progression-related endpoints were evaluated. The impact of vutrisiran over 36 months on outpatient worsening HF and an expanded composite of ACM, recurrent CV events, and outpatient worsening HF was also assessed.

Results

In the overall population (n=655 randomized; n=654 treated), 321 (49.1%) patients had ≥1 outpatient worsening HF event, 245 (37.5%) had ≥1 CV event(s), and 120 (18.3%) died; 237 patients (36.2%) had no events. Patients with, vs those without, outpatient worsening HF had an increased risk of ACM and CV events (hazard ratio [HR] 2.58, 95% confidence interval [CI] 2.04–3.27) and ACM (HR 2.45, 95% CI 1.70–3.52) (Figure 1), as well as greater deterioration in 6-minute walk test distance and Kansas City Cardiomyopathy Questionnaire-Overall Summary score, and a greater increase in N-terminal prohormone of B-type natriuretic peptide. In recurrent event analyses over the double-blind period, vutrisiran reduced the rate of outpatient worsening HF (relative rate ratio 0.66, 95% CI 0.56–0.78) vs placebo. Vutrisiran also reduced the risk of the composite of ACM, recurrent CV events and outpatient worsening HF vs placebo (HR 0.69 [95% CI 0.57–0.83]) (Figure 2).

Conclusions

Outpatient worsening HF was frequent in patients with ATTR-CM and was associated with an increased risk of mortality and recurrent CV events. Vutrisiran reduced the risk of outpatient worsening HF vs placebo.

This abstract has been presented at AHA 2024, Nov 16–18, 2024, Chicago, IL.

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在HELIOS-B试验中，Vutrisiran对转甲状腺蛋白淀粉样变合并心肌病患者门诊心力衰竭恶化的影响

转甲状腺蛋白淀粉样变合并心肌病（atr - cm）是一种由转甲状腺蛋白淀粉样纤维沉积在心脏引起的致命疾病。需要实用和敏感的方法来监测患者的疾病进展和优化治疗决策。门诊心衰恶化（口服利尿剂强化或开始）已被证明是atr - cm患者死亡率的预后因素。在3期helos - b试验（NCT04153149）中，RNAi治疗的vutrisiran与安慰剂相比，降低了atr - cm患者的全因死亡率（ACM）和复发性CV事件（CV住院和紧急HF就诊）的风险。目的探讨乌曲西兰对atr - cm患者门诊心衰恶化的临床及预后价值。方法评估门诊心衰恶化与HELIOS-B主要复合ACM和复发性CV事件、单独ACM和其他疾病进展相关终点之间的关系。我们还评估了36个月以上vutrisiran对门诊心衰恶化的影响，以及ACM、复发性CV事件和门诊心衰恶化的扩大复合效应。结果在总人群中(n=655，随机；n=654例接受治疗的患者)，321例（49.1%）患者有≥1例门诊心衰恶化事件，245例（37.5%）患者有≥1例CV事件，120例（18.3%）患者死亡；237例（36.2%）无不良事件发生。门诊加重心衰患者与未加重心衰患者相比，发生ACM和CV事件的风险增加（风险比[HR] 2.58, 95%可信区间[CI] 2.04-3.27）和ACM（风险比[HR] 2.45, 95% CI 1.70-3.52）（图1），6分钟步行测试距离和堪萨斯城心肌病问卷-总体总结评分恶化更大，b型利钠肽n端原激素增加更大。在双盲期间的复发事件分析中，与安慰剂相比，vutrisiran降低了门诊心衰恶化率（相对率比0.66,95% CI 0.56-0.78）。与安慰剂相比，Vutrisiran还降低了ACM、复发性CV事件和门诊HF恶化的综合风险（HR 0.69 [95% CI 0.57-0.83]）（图2）。结论门诊心衰恶化在atr - cm患者中很常见，并与死亡率和复发性心血管事件的风险增加相关。与安慰剂相比，Vutrisiran降低了门诊心衰恶化的风险。该摘要发表于AHA 2024年11月16-18日，芝加哥，伊利诺伊州。

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来源期刊

Heart & Lung 医学-呼吸系统

CiteScore

4.60

自引率

3.60%

发文量

184

审稿时长

35 days

期刊介绍： Heart & Lung: The Journal of Cardiopulmonary and Acute Care, the official publication of The American Association of Heart Failure Nurses, presents original, peer-reviewed articles on techniques, advances, investigations, and observations related to the care of patients with acute and critical illness and patients with chronic cardiac or pulmonary disorders. The Journal''s acute care articles focus on the care of hospitalized patients, including those in the critical and acute care settings. Because most patients who are hospitalized in acute and critical care settings have chronic conditions, we are also interested in the chronically critically ill, the care of patients with chronic cardiopulmonary disorders, their rehabilitation, and disease prevention. The Journal''s heart failure articles focus on all aspects of the care of patients with this condition. Manuscripts that are relevant to populations across the human lifespan are welcome.