Effect of Acoramidis on Recurrent and Cumulative Cardiovascular Outcomes in ATTR-CM: Exploratory Analysis From ATTRibute-CM.

Acoramidis, an approved oral therapy for ATTR-CM, achieves early, near-complete (≥90%) TTR stabilization.

Acoramidis是一种已批准的ATTR-CM口服疗法，能够实现早期、接近完全（≥90%）的TTR稳定。

In the phase 3 ATTRibute-CM (Efficacy and Safety of Acoramidis in Participants with Transthyretin Amyloid Cardiomyopathy) study, acoramidis significantly reduced the composite of all-cause mortality or first CV-related hospitalization (CVH), with an effect observed at month 3.

在第3阶段ATTRibute-CM（Acoramidis在转甲状腺素淀粉样变性心肌病患者中的疗效和安全性）研究中，Acoramidis显著降低了全因死亡或首次心血管相关住院（CVH）的复合终点，这种效果在第3个月就被观察到。

Its efficacy on the burden of cumulative CV outcome events has not been reported.

其对累积心血管结果事件负担的疗效尚未被报道。

This study was a post hoc exploratory recurrent-event analysis of the efficacy of acoramidis on the cumulative incidenceof CV outcomes from ATTRibute-CM and its open-label extension.

本研究是对acoramidis在ATTRibute-CM及其开放标签扩展研究中对心血管事件累积发生率影响的事后探索性复发事件分析。

Methods

Cumulative incidences of centrally adjudicated CV-related mortality (CVM) or recurrent CVH (first and, if applicable, subsequent CVH), recurrent CVH alone (month 30), and CVM (month 42) were measured in the modified intention-to-treatpopulation (acoramidis, n = 409; placebo, n = 202).

在修改后的意向治疗人群中测量了中心评估的心血管相关死亡（CVM）或复发性心血管事件（首次及如有后续事件）的累积发生率，仅复发性心血管事件（第30个月），以及CVM（第42个月），acoramidis组为409人，安慰剂组为202人。

Mean cumulative events by treatment, and the difference between treatment groups were estimated by using a modified Andersen-Gill model.

通过使用改良的Andersen-Gill模型估计了治疗组的平均累积事件数以及治疗组之间的差异。

Results

Acoramidis significantly reduced the cumulative risk of CVM or recurrent CVH through month 30 vs placebo (HR: 0.51; 95% CI: 0.43-0.62; P < 0.0001).

Acoramidis在30个月内显著降低了CVM或复发性CVH的累积风险，与安慰剂相比（HR: 0.51; 95% CI: 0.43-0.62; P < 0.0001）。

A notable proportion of CV outcome events (19% of CVM or recurrent CVH events, 22% of CVH) occurred within the first 6 months.

值得注意的是，心血管结局事件中有相当比例（19%的心血管死亡或复发性心血管事件，22%的心血管事件）发生在最初的6个月内。

Numerically fewer cumulative events were observed with acoramidis compared with placebo at month 1, and the difference increased progressively, resulting at month 30 in 53 events avoided per 100 treated participants (95% CI: 29-79).

与安慰剂相比，acoramidis在第1个月观察到的累积事件数量较少，差异逐渐增大，到第30个月时，每100名接受治疗的参与者避免了53次事件（95%置信区间：29-79）。

At month 42, CVM was reduced with continuous acoramidis vs placebo-to-acoramidis (HR: 0.55; 95% CI: 0.39-0.79; P = 0.0011).

在第42个月时，与安慰剂转为acoramidis相比，持续使用acoramidis可降低CVM（风险比：0.55；95%置信区间：0.39-0.79；P = 0.0011）。

The annualized frequency of recurrent CVH was significantly decreased through month 30 (relative risk ratio: 0.50; 95% CI: 0.35-0.69; P < 0.0001).

在第30个月时，复发性CVH的年化频率显著降低（相对风险比：0.50；95%置信区间：0.35-0.69；P < 0.0001）。

Conclusions

Acoramidis significantly reduced the cumulative burden of CV outcomes in ATTR-CM over 30 months.

Acoramidis显著降低了ATTR-CM患者在30个月内的心血管事件累积负担。

Numerically fewer events were observed with acoramidis vs placebo by month 1, and the difference increased progressively over time, resulting in 53 events avoided per 100 treated patients at month 30.

与安慰剂相比，从第1个月开始观察到acoramidis的事件数量较少，并且随着时间的推移差异逐渐增大，到第30个月时，每100名接受治疗的患者避免了53次事件。

Almost one-fourth of the cumulative CV events occurred within the first 6 months.

近四分之一的心血管事件累积发生在前6个月内。

These exploratory findings suggest that cumulative event burden may occur early, highlighting the importance of timely evaluation, diagnosis and treatment in ATTR-CM.

这些探索性发现表明，累积事件负担可能早期发生，强调了在ATTR-CM中及时评估、诊断和治疗的重要性。