BACKGROUND

Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a fatal disease, caused by misfolded transthyretin depositing as amyloid fibrils in the heart. Because disease progression is common, practical and sensitive methods are needed to monitor patients and optimize treatment decisions. Outpatient worsening heart failure (HF) (oral loop diuretic intensification or initiation) is simple to assess and has been shown to be prognostic of mortality in patients with ATTR-CM.

OBJECTIVES

We aimed to assess the clinical and prognostic significance of and the effect of vutrisiran treatment on outpatient worsening HF in patients with ATTR-CM from the HELIOS-B trial.

METHODS

Associations between outpatient worsening HF and a composite of all-cause mortality and recurrent cardiovascular (CV) events (CV hospitalizations and urgent HF visits), all-cause mortality, and other disease progression-related endpoints were evaluated. The impact of vutrisiran over 36 months on outpatient worsening HF and an expanded composite of all-cause mortality, recurrent CV events, and outpatient worsening HF was also assessed.

RESULTS

Overall, 321 patients (49.1%) had ≥1 outpatient worsening HF, 245 (37.5%) had ≥1 CV event(s), and 120 (18.3%) died; 237 patients (36.2%) had no events. Patients with outpatient worsening HF had an increased risk of all-cause mortality and CV events (hazard ratio [HR]: 2.58; 95% confidence interval [CI]: 2.04-3.27) and all-cause mortality (HR: 2.45; 95% CI: 1.70-3.52), as well as a 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 versus placebo reduced the rate of outpatient worsening HF (relative rate ratio: 0.66; 95% CI: 0.56-0.78). Vutrisiran also reduced the risk of the composite of all-cause mortality, CV events, and outpatient worsening HF versus placebo (HR: 0.69; 95% CI: 0.57-0.83).

CONCLUSIONS

Outpatient worsening HF was frequent in patients with ATTR-CM in HELIOS-B, and was associated with increased mortality, and reduced by vutrisiran.

中文翻译：

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HELIOS-B 试验中转甲状腺素蛋白淀粉样变性伴心肌病患者的门诊心力衰竭恶化

 背景

转甲状腺素蛋白淀粉样变性伴心肌病 （ATTR-CM） 是一种致命的疾病，由错误折叠的转甲状腺素蛋白以淀粉样蛋白原纤维的形式沉积在心脏中引起。由于疾病进展很常见，因此需要实用且敏感的方法来监测患者并优化治疗决策。门诊恶化的心力衰竭 （HF） （口服袢利尿剂强化或启动） 易于评估，并且已被证明是 ATTR-CM 患者死亡的预后。

 目标

我们旨在评估 HELIOS-B 试验中 vutrisiran 治疗对门诊 ATTR-CM 患者 HF 恶化的临床和预后意义和影响。

 方法

评估门诊 HF 恶化与全因死亡率和复发性心血管 （CV） 事件 （CV 住院和 HF 紧急就诊） 、全因死亡率和其他疾病进展相关终点的复合之间的关联。还评估了 vutrisiran 超过 36 个月对门诊恶化 HF 的影响，以及全因死亡率、复发性 CV 事件和门诊恶化 HF 的扩展复合。

 结果

总体而言，321 例患者 （49.1%） 门诊 ≥1 例 HF 恶化，245 例 （37.5%） ≥1 例 CV 事件，120 例 （18.3%） 死亡;237 例患者 （36.2%） 无事件。门诊 HF 恶化患者全因死亡和 CV 事件的风险增加 （风险比 [HR]： 2.58;95% 置信区间 [CI]： 2.04-3.27） 和全因死亡率 （HR： 2.45;95% CI： 1.70-3.52），以及 6 分钟步行测试距离和堪萨斯城心肌病问卷 - 总体总分的恶化程度更高，N 的增加幅度更大-B 型利钠肽的末端激素原。在双盲期的复发事件分析中，vutrisiran 与安慰剂相比降低了门诊 HF 恶化的发生率（相对比率：0.66;95% CI：0.56-0.78）。与安慰剂相比，Vutrisiran 还降低了全因死亡率、CV 事件和门诊 HF 恶化的复合风险 （HR： 0.69;95% CI： 0.57-0.83）。

 结论

HELIOS-B 中的 ATTR-CM 患者门诊 HF 恶化很常见，并且与死亡率增加相关，并通过 vutrisiran 降低。