Witteles Ronald M, Garcia-Pavia Pablo, Damy Thibaud, Grogan Martha, Sheikh Farooq H, Morbach Caroline, Bender Shaun, Exter Jason, Eraly Satish A, Fontana Marianna
Division of Cardiovascular Medicine and Stanford Amyloid Center, Stanford University School of Medicine, Stanford, California, USA.
Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, IDIPHISA, CIBERCV, and Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
J Am Coll Cardiol. 2025 Apr 30. doi: 10.1016/j.jacc.2025.04.008.
Patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) have high mortality and morbidity. Vutrisiran, a subcutaneous RNA interference therapeutic, reduced the composite of all-cause mortality (ACM) and cardiovascular (CV) events (CV hospitalizations and urgent heart failure [HF] visits) in HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy) in patients with ATTR-CM.
Here we present data from HELIOS-B evaluating the impact of vutrisiran on ACM and CV mortality with additional patient follow-up through 42 months, and CV events such as CV hospitalizations, HF hospitalizations, and urgent HF visits.
The HELIOS-B trial randomized 655 patients to vutrisiran 25 mg or placebo once every 3 months for up to 33 to 36 months in the double-blind (DB) period, followed by an open-label extension. Prespecified mortality and CV mortality analyses used data through 39 to 42 months of follow-up (DB period and up to 6 months of the open-label extension). CV hospitalizations and HF events were evaluated over the DB period of 33 to 36 months. Differences between vutrisiran and placebo were evaluated in the overall population, and in those stratified by baseline tafamidis use.
In the overall population, vutrisiran reduced the risk of ACM (HR: 0.64; 95% CI: 0.46-0.88) and CV mortality (HR: 0.67; 95% CI: 0.47-0.96) vs placebo. Vutrisiran also reduced the risk of a composite of CV mortality and CV events (HR: 0.72; 95% CI: 0.55-0.94), and lowered rates of CV hospitalizations (rate ratio [RR]: 0.75; 95% CI: 0.62-0.91), urgent HF visits (RR: 0.54; 95% CI: 0.30-0.98), and HF hospitalizations (RR: 0.67; 95% CI: 0.52-0.86) vs placebo. Consistent trends were seen regardless of baseline tafamidis use.
Consistent with the primary trial results, vutrisiran reliably reduced the risk of ACM, CV mortality, CV hospitalizations, HF hospitalizations, and urgent HF visits vs placebo in patients with ATTR-CM. (HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy; NCT04153149).
转甲状腺素蛋白淀粉样变心肌病（ATTR-CM）患者的死亡率和发病率很高。皮下注射RNA干扰疗法vutrisiran在HELIOS-B（一项评估vutrisiran治疗转甲状腺素蛋白淀粉样变心肌病患者的研究）中降低了ATTR-CM患者的全因死亡率（ACM）和心血管（CV）事件（CV住院和紧急心力衰竭[HF]就诊）的综合发生率。
在此，我们展示HELIOS-B的数据，评估vutrisiran对ACM和CV死亡率的影响，并对患者进行长达42个月的额外随访，同时评估CV事件，如CV住院、HF住院和紧急HF就诊。
HELIOS-B试验将655例患者随机分为vutrisiran 25mg组或安慰剂组，每3个月给药一次，双盲期长达33至36个月，随后进行开放标签扩展。预先设定的死亡率和CV死亡率分析使用了随访39至42个月（双盲期和开放标签扩展期长达6个月）的数据。在33至36个月的双盲期内评估CV住院和HF事件。在总体人群以及根据基线使用tafamidis分层的人群中评估vutrisiran与安慰剂之间的差异。
在总体人群中，与安慰剂相比，vutrisiran降低了ACM风险（风险比[HR]：0.64；95%置信区间[CI]：0.46-0.88）和CV死亡率（HR：0.67；95%CI：0.47-0.96）。vutrisiran还降低了CV死亡率和CV事件综合发生率的风险（HR：0.72；95%CI：0.55-0.94），并降低了CV住院率（率比[RR]：0.75；95%CI：0.62-0.91）、紧急HF就诊率（RR：0.54；95%CI：0.30-0.98）和HF住院率（RR：0.67；95%CI：0.52-0.86）。无论基线是否使用tafamidis，均观察到一致的趋势。
与主要试验结果一致，在ATTR-CM患者中，与安慰剂相比，vutrisiran可靠地降低了ACM、CV死亡率、CV住院、HF住院和紧急HF就诊的风险。（HELIOS-B：一项评估vutrisiran治疗转甲状腺素蛋白淀粉样变心肌病患者的研究；NCT04153149）
