Introduction

ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial) demonstrated the efficacy and safety of tafamidis in transthyretin amyloid cardiomyopathy (ATTR-CM). Model-based analyses from ATTR-ACT can examine predictor effects on dose–response/exposure–response relationships.

Methods

Parametric hazard distributions were developed for all-cause mortality and frequency of cardiovascular-related hospitalization. Time-to-event models were fitted to survival data, and repeated time-to-event models were fitted to hospitalization data. Disease-specific characteristics were assessed as baseline predictors of event hazards.

Results

There were 441 patients in this analysis. At month 30, 70.5% (tafamidis) and 57.1% (placebo) of patients were alive, with 154/441 deaths reported; 495 cardiovascular-related hospitalizations occurred. The cumulative risk of death was 42.1% (95% confidence interval [CI] 24.2–58.0) lower with tafamidis than with placebo, regardless of New York Heart Association (NYHA) class; significant predictors of decreased risk were genotype (wild-type), greater 6-Minute Walk Test (6MWT) distance, higher left ventricular ejection fraction (LVEF), and lower blood urea nitrogen (BUN) and N-terminal pro-B-type natriuretic peptide concentrations. The average cumulative risk of cardiovascular-related hospitalization up to 30 months was 40.8% (95% CI 31.0–49.7) lower with tafamidis in NYHA class I/II patients. Significant predictors of reduced risk were greater 6MWT distance, higher LVEF, and lower BUN and troponin I concentrations.

Conclusions

Tafamidis reduced cumulative mortality and hospitalization risk versus placebo in patients with ATTR-CM. Baseline predictors of outcome were consistent with the cardiovascular nature of the disease and suggested that earlier treatment may improve outcomes.

Clinical Trials.gov Identifier

NCT01994889 (date of registration: November 26, 2013).

中文翻译：

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用 Tafamidis 治疗的转甲状腺素蛋白淀粉样蛋白心肌病患者的生存率和心血管相关住院频率的建模

介绍

ATTR-ACT（Tafamidis 在转甲状腺素蛋白心肌病临床试验中）证明了 tafamidis 在转甲状腺素蛋白淀粉样蛋白心肌病（ATTR-CM）中的疗效和安全性。ATTR-ACT 的基于模型的分析可以检查预测因子对剂量-反应/暴露-反应关系的影响。

方法

为全因死亡率和心血管相关住院频率制定了参数风险分布。事件发生时间模型拟合生存数据，重复事件发生时间模型拟合住院数据。疾病特异性特征被评估为事件危害的基线预测因子。

结果

在这项分析中有 441 名患者。在第 30 个月时，70.5%（tafamidis）和 57.1%（安慰剂）的患者存活，报告有 154/441 例死亡；发生 495 例心血管相关住院。无论纽约心脏协会 (NYHA) 等级如何，tafamidis 组的累积死亡风险比安慰剂组低 42.1%（95% 置信区间 [CI] 24.2–58.0）；风险降低的显着预测因子是基因型（野生型）、更大的 6 分钟步行测试 (6MWT) 距离、更高的左心室射血分数 (LVEF) 以及更低的血尿素氮 (BUN) 和 N 末端前 B 型利钠肽浓度。在 NYHA I/II 级患者中，使用 tafamidis 后 30 个月内心血管相关住院的平均累积风险降低了 40.8% (95% CI 31.0–49.7)。

结论

与安慰剂相比，Tafamidis 降低了 ATTR-CM 患者的累积死亡率和住院风险。结果的基线预测因子与疾病的心血管性质一致，并表明早期治疗可能会改善结果。

Clinical Trials.gov 标识符

NCT01994889（注册日期：2013 年 11 月 26 日）。