本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2305434

摘要内容如下：

背景

甲状腺素运载蛋白淀粉样心肌病的特征是在心脏中沉积错误折叠的单体甲状腺素运载蛋白（TTR）。Acoramidis是一种高亲和力TTR稳定剂，其作用是抑制四聚体TTR的解离，并导致在整个给药间隔中超过90%的稳定性（如离体测量）。

方法

在这项3期、双盲试验中，我们将甲状腺素运载蛋白淀粉样心肌病患者以2:1的比例随机分配接受盐酸阿可拉米斯（剂量为800 mg，每日两次）或匹配的安慰剂治疗30个月。在估计肾小球滤过率至少为每分钟30 mL/1.73 m2体表面积的患者中评估疗效。四步初步分层分析包括任何原因导致的死亡、心血管相关住院、N末端B型利钠肽前体（NT-proBNP）水平相对于基线的变化以及6分钟步行距离相对于基线的变化。我们使用Finkelstein-Schoenfeld方法来比较地层内所有可能的患者对，以生成P值。关键的次要转归是任何原因导致的死亡、6分钟步行距离、堪萨斯城心肌病问卷-总体总结评分和血清TTR水平。

结果

共有632名患者接受了随机分组。与安慰剂相比，主要分析更倾向于使用菖蒲（P<0.001）；相应的赢率为1.8（95%可信区间[CI]，1.4至2.2），63.7%的两两比较支持菖蒲，35.9%支持安慰剂。总之，任何原因导致的死亡和心血管相关的住院治疗对赢率的输赢贡献超过一半（所有配对比较的58%）；NT-proBNP两两比较产生了最高的胜负比（23.3%vs.7.0%）。总的不良事件发生率在菖蒲组和安慰剂组相似（分别为98.1%和97.6%）；54.6%和64.9%的患者报告了严重不良事件。

结论

在甲状腺素运载蛋白淀粉样心肌病患者中，与安慰剂相比，接受Acoramidis治疗可产生显著更好的四步主要分级结果，包括死亡率、发病率和功能。两组不良事件相似。（由BridgeBio Pharma资助；Attribute-CM ClinicalTrials.gov编号，NCT03860935。）

英文原文如下：

Abstracts

BACKGROUND  Transthyretin amyloid cardiomyopathy is characterized by the deposition of misfolded monomeric transthyretin (TTR) in the heart. Acoramidis is a high-affinity TTR stabilizer that acts to inhibit dissociation of tetrameric TTR and leads to more than 90% stabilization across the dosing interval as measured ex vivo.

METHODS  In this phase 3, double-blind trial, we randomly assigned patients with transthyretin amyloid cardiomyopathy in a 2:1 ratio to receive acoramidis hydrochloride at a dose of 800 mg twice daily or matching placebo for 30 months. Efficacy was assessed in the patients who had an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area. The four-step primary hierarchical analysis included death from any cause, cardiovascular-related hospitalization, the change from baseline in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and the change from baseline in the 6-minute walk distance. We used the Finkelstein-Schoenfeld method to compare all potential pairs of patients within strata to generate a P value. Key secondary outcomes were death from any cause, the 6-minute walk distance, the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary, and the serum TTR level.

RESULTS  A total of 632 patients underwent randomization. The primary analysis favored acoramidis over placebo (P<0.001); the corresponding win ratio was 1.8 (95% confidence interval [CI], 1.4 to 2.2), with 63.7% of pairwise comparisons favoring acoramidis and 35.9% favoring placebo. Together, death from any cause and cardiovascular-related hospitalization contributed more than half the wins and losses to the win ratio (58% of all pairwise comparisons); NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3% vs. 7.0%). The overall incidence of adverse events was similar in the acoramidis group and the placebo group (98.1% and 97.6%, respectively); serious adverse events were reported in 54.6% and 64.9% of the patients.

CONCLUSIONS  In patients with transthyretin amyloid cardiomyopathy, the receipt of acoramidis resulted in a significantly better four-step primary hierarchical outcome containing components of mortality, morbidity, and function than placebo. Adverse events were similar in the two groups. (Funded by BridgeBio Pharma; ATTRibute-CM ClinicalTrials.gov number, NCT03860935.).

-----------分割线---------

点击链接：https://www.mediecogroup.com/community/user/vip/categories/ ，成为医咖会员，获取12项专属权益。

现在购买可享受最大优惠（买一年送三个月，买两年送一年），2024年2月10日起将不再享有该优惠。