Wixner Jonas, Dispenzieri Angela, Amass Leslie, Carlsson Martin, Riley Steve, Powers Evan, Kelly Jeffery W
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Department of Medicine, Umeå University Hospital, Akutvägen 1, 90185, Umeå, Sweden.
Cardiol Ther. 2025 Jul 9. doi: 10.1007/s40119-025-00421-9.
Tafamidis is approved to treat transthyretin amyloid cardiomyopathy (ATTR-CM). Many patients with ATTR-CM present with a mixed phenotype of both cardiac and neurologic symptoms, but real-world effectiveness studies of tafamidis in this population are lacking. This study assessed survival and other outcomes in a real-world, contemporary cohort of tafamidis-treated and untreated patients with mixed-phenotype ATTR-CM.
The Transthyretin Amyloidosis Outcomes Survey (THAOS) was a longitudinal, observational, phase 4 study of patients with transthyretin amyloidosis and asymptomatic carriers of pathogenic transthyretin gene variants and was completed in June 2023. This analysis included a contemporary cohort of patients enrolled in THAOS in 2019-2023 who were characterized as having mixed-phenotype ATTR-CM at enrollment. The tafamidis-treated cohort received the approved dose of tafamidis (meglumine 80 mg/free acid 61 mg) throughout the study, and the untreated cohort never received tafamidis.
In tafamidis-treated (n = 116) and untreated patients (n = 223), respectively, median age at enrollment was 77.8 and 72.8 years, and 42.2% and 77.6% had variant ATTR-CM. Survival rates at 30 months were 81.5% (95% CI 66.7-90.2) in tafamidis-treated patients and 75.1% (95% CI 66.1-82.0) in untreated patients. Median yearly incidence of cardiovascular-related hospitalizations was 0.89 for tafamidis-treated and 1.70 for untreated patients, and median duration of cardiovascular-related hospitalizations was 7.0 and 11.5 days, respectively. There were 13 (11.2%) and 40 (17.9%) deaths in the respective groups.
Patients with mixed-phenotype ATTR-CM treated with the approved dose of tafamidis had numerically higher survival rates, a numerically lower rate of cardiovascular-related hospitalizations, and fewer deaths than untreated patients. These data parallel recent results for patients with predominantly cardiac ATTR-CM from THAOS and extend results of ATTR-ACT to a contemporary, real-world, mixed-phenotype population.
ClinicalTrials.gov identifier NCT00628745.
他法米地已获批用于治疗转甲状腺素蛋白淀粉样变心肌病（ATTR-CM）。许多ATTR-CM患者同时表现出心脏和神经症状的混合表型，但缺乏他法米地在该人群中的真实世界有效性研究。本研究评估了在真实世界中，接受他法米地治疗和未接受治疗的混合表型ATTR-CM当代队列患者的生存率和其他结局。
转甲状腺素蛋白淀粉样变结局调查（THAOS）是一项针对转甲状腺素蛋白淀粉样变患者以及致病性转甲状腺素蛋白基因变异无症状携带者的纵向、观察性4期研究，于2023年6月完成。该分析纳入了2019 - 2023年参加THAOS的当代队列患者，这些患者在入组时被判定为具有混合表型ATTR-CM。接受他法米地治疗的队列在整个研究过程中接受批准剂量的他法米地（葡甲胺80mg/游离酸61mg），未治疗队列从未接受过他法米地治疗。
在接受他法米地治疗的患者（n = 116）和未接受治疗的患者（n = 223）中，入组时的中位年龄分别为77.8岁和72.8岁，分别有42.2%和77.6%的患者患有变异型ATTR-CM。接受他法米地治疗的患者30个月时的生存率为81.5%（95%CI 66.7 - 90.2），未接受治疗的患者为75.1%（95%CI 66.1 - 82.0）。接受他法米地治疗的患者心血管相关住院的年中位发生率为0.89，未接受治疗的患者为1.70，心血管相关住院的中位持续时间分别为7.0天和11.5天。两组分别有13例（11.2%）和40例（17.9%）死亡。
接受批准剂量他法米地治疗的混合表型ATTR-CM患者在数值上比未接受治疗患者的生存率更高，心血管相关住院率在数值上更低，死亡人数更少。这些数据与THAOS中主要为心脏型ATTR-CM患者的近期结果相似，并将ATTR-ACT的结果扩展到了当代真实世界的混合表型人群。
ClinicalTrials.gov标识符NCT00628745。
