Effect of Vutrisiran According to Baseline Tafamidis Use in Transthyretin Amyloidosis With Cardiomyopathy: Insights From HELIOS-B.

Tafamidis, a transthyretin stabilizer, also improves clinical outcomes.

Tafamidis，一种甲状腺转运蛋白稳定剂，也能改善临床结果。

Although combining these therapies is mechanistically appealing, clinical evidence supporting this approach is limited.

尽管将这些疗法结合在理论上是有吸引力的，但支持这种方法的临床证据有限。

We sought to evaluate whether the treatment effects of vutrisiran differed according to baseline tafamidis use in HELIOS-B.

我们试图评估在HELIOS-B研究中，vutrisiran的治疗效果是否根据基线时是否使用tafamidis而有所不同。

Methods

In HELIOS-B, patients with ATTR-CM were randomized to vutrisiran 25 mg or placebo every 3 months for up to 36 months, with tafamidis use permitted and stratified.

在HELIOS-B研究中， ATTR-CM患者被随机分配接受每3个月一次25毫克的vutrisiran或安慰剂，最长可达36个月，允许并按tafamidis使用情况进行分层。

We assessed treatment effects according to baseline tafamidis use for the primary outcome of all-cause mortality and recurrent cardiovascular events and secondary endpoints, including individual components of the primary outcome, composite of all-cause mortality, cardiovascular events and outpatient worsening heart failure events, functional capacity (6-minute walk distance), and health status (Kansas City Cardiomyopathy Questionnaire-overall summary score [KCCQ-OSS]).

我们根据基线时是否使用tafamidis，评估了全因死亡率和复发性心血管事件的主要结果，以及包括主要结果的各个组成部分、全因死亡率、心血管事件和门诊恶化心力衰竭事件的复合结果、功能能力（6分钟步行距离）和健康状况（堪萨斯城心肌病问卷总体总结评分[KCCQ-OSS]）的次要终点。

Results

Among 654 participants, 259 (40%) were receiving tafamidis at baseline.

在654名参与者中，有259名（40%）在基线时正在使用tafamidis。

Patients on tafamidis were slightly younger and had higher baseline 6-minute walk distance and higher KCCQ-OSS, while baseline characteristics were generally balanced between randomized groups.

正在使用tafamidis的患者年龄略低，基线时的6分钟步行距离更高，KCCQ-OSS更高，而随机分组之间的基线特征总体上是平衡的。

The treatment effect estimates of vutrisiran compared with placebo for the primary outcome were directionally consistent across baseline tafamidis strata (rate ratio: 0.79 [95% CI: 0.51-1.21] with tafamidis vs 0.67 [95% CI: 0.49-0.93] without), with no statistically significant interaction (Pinteraction = 0.55).

Vutrisiran与安慰剂相比，主要结果的治疗效果估计在基线Tafamidis分层中是一致的（率比：0.79 [95% CI: 0.51-1.21] 有Tafamidis vs 0.67 [95% CI: 0.49-0.93] 无），没有统计学上的显著交互作用（Pinteraction = 0.55）。

Similar patterns were observed for all-cause mortality, cardiovascular events, and outpatient worsening heart failure (all Pinteraction > 0.20), although the magnitudes of the estimated effects were numerically smaller among patients receiving tafamidis at baseline.

所有原因的死亡率、心血管事件和门诊心力衰竭恶化观察到了类似模式，尽管基线接受Tafamidis治疗的患者的估计效果数值上较小（所有Pinteraction > 0.20）。

Vutrisiran preserved 6-minute walk distance in both baseline tafamidis strata (Pinteraction = 0.24), whereas improvement in KCCQ-OSS appeared attenuated among patients receiving tafamidis at baseline.

Vutrisiran在两个基线Tafamidis分层中都保持了6分钟步行距离（Pinteraction = 0.24），而KCCQ-OSS的改善在基线接受Tafamidis治疗的患者中似乎减弱。

Conclusions

Treatment effect estimates for vutrisiran on clinical outcomes were consistent across baseline tafamidis strata, with no statistically significant interaction according to baseline tafamidis use, with reduced effect size noted in those receiving baseline stabilizers in comparison to monotherapy.

Vutrisiran对临床结果的治疗效果估计在基线Tafamidis分层中是一致的，没有统计学上的显著交互作用，根据基线Tafamidis使用情况，与单药治疗相比，基线稳定剂接受者的效应大小有所减少。

These data underscore the need for future prospective studies examining combination therapy in this population.

这些数据强调了未来需要进行前瞻性研究，以检查这一人群中的联合治疗。

(HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy; NCT04153149).

(HELIOS-B: 一项评估Vutrisiran在患有心脏淀粉样变性的转甲状腺素淀粉样变性患者中的研究; NCT04153149).