Survival in a Real-World Cohort of Patients With Transthyretin Amyloid Cardiomyopathy Treated With Tafamidis: An Analysis From the Transthyretin Amyloidosis Outcomes Survey (THAOS)

IF 6.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of Cardiac Failure Pub Date : 2025-03-01 DOI:10.1016/j.cardfail.2024.06.003

PABLO GARCIA-PAVIA MD, PhD , ARNT V. KRISTEN MD , BRIAN DRACHMAN MD , MARTIN CARLSSON MS , LESLIE AMASS PhD , FRANCA STEDILE ANGELI MD, PhD , MATHEW S. MAURER MD , THAOS investigators

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Abstract

Background

In the pivotal Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis significantly reduced mortality rates, leading to its approval in many countries for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). Real-world evidence on survival in patients with ATTR-CM following tafamidis treatment has not been extensively reported.

Methods and Results

The Transthyretin Amyloidosis Outcomes Survey (THAOS) was a longitudinal, observational, phase 4 study of patients with transthyretin amyloidosis and asymptomatic participants carrying pathogenic transthyretin variants. Patients from THAOS with a predominantly cardiac phenotype at enrollment were included, and survival was analyzed according to tafamidis treatment status (treated or untreated). Results are based on the completed THAOS dataset. In tafamidis-treated (n = 587) and tafamidis-untreated (n = 854) patients, respectively, median age at enrollment was 77.7 and 76.4 years, 91.8% and 90.0% were male, and 91.8% and 83.8% had wild-type disease. Survival rates (95% CI) at 30 and 42 months, respectively, were 84.4% (80.5–87.7) and 76.8% (70.9–81.7) in tafamidis-treated patients, and 70.0% (66.4-73.2) and 59.3% (55.2-63.0) in tafamidis-untreated patients. Survival rates in genotype subgroups (wild-type and variant) were similar to those of the overall cohort. Survival rates were better in a contemporary cohort, as reflected by a sensitivity analysis performed in patients enrolled after vs before 2019. No new safety signals were identified.

Conclusions

In this real-world cohort of patients with ATTR-CM, survival rates were higher than in ATTR-ACT and consistent with more recent reports, suggesting early diagnosis and treatment with tafamidis has improved life expectancy in ATTR-CM. These results provide further evidence supporting tafamidis’ safety and effectiveness.

Trial registration: ClinicalTrials.gov identifier: NCT00628745

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经淀粉样蛋白淀粉样变性心肌病患者接受塔法米地治疗后的实际生存情况：经淀粉样蛋白淀粉样变性结果调查 (THAOS) 分析。

背景：在关键的塔法米地斯治疗转甲状腺素心肌病临床试验（ATTR-ACT）中，塔法米地斯显著降低了死亡率，因此许多国家批准其用于治疗转甲状腺素淀粉样心肌病（ATTR-CM）。有关经淀粉样蛋白淀粉样心肌病（ATTR-CM）患者接受他伐米迪治疗后的存活率的实际证据尚未得到广泛报道：转甲状腺素淀粉样变性结果调查（THAOS）是一项针对转甲状腺素淀粉样变性患者和携带致病性转甲状腺素变体的无症状参与者的纵向观察性四期研究。研究纳入了入组时以心脏表型为主的 THAOS 患者，并根据他法米迪治疗状态（治疗或未治疗）分析了患者的存活率。结果基于完整的 THAOS 数据集。在接受过他法米迪治疗（587人）和未接受过他法米迪治疗（854人）的患者中，入组时的中位年龄分别为77.7岁和76.4岁，91.8%和90.0%为男性，91.8%和83.8%为野生型疾病患者。他法米迪治疗患者在30个月和42个月时的存活率（95% CI）分别为84.4%（80.5-87.7）和76.8%（70.9-81.7），而他法米迪未治疗患者的存活率分别为70.0%（66.4-73.2）和59.3%（55.2-63.0）。基因型亚组（野生型和变异型）的存活率与总体队列相似。对2019年之后和之前入组的患者进行的敏感性分析表明，现代队列的存活率更高。未发现新的安全性信号：在这个真实世界的ATTR-CM患者队列中，生存率高于ATTR-ACT，与最近的报道一致，表明早期诊断和他法米迪治疗改善了ATTR-CM患者的预期寿命。这些结果进一步证明了他法米迪的安全性和有效性：试验注册：ClinicalTrials.gov identifier：NCT00628745。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cardiac Failure 医学-心血管系统

CiteScore

7.80

自引率

8.30%

发文量

653

审稿时长

21 days

期刊介绍： Journal of Cardiac Failure publishes original, peer-reviewed communications of scientific excellence and review articles on clinical research, basic human studies, animal studies, and bench research with potential clinical applications to heart failure - pathogenesis, etiology, epidemiology, pathophysiological mechanisms, assessment, prevention, and treatment.