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. 2025 Jul 9.
doi: 10.1007/s40119-025-00421-9. Online ahead of print.

Survival in a Contemporary, Real-World Cohort of Patients with Mixed-Phenotype Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis: An Analysis from THAOS

Jonas Wixner  1   2 , Angela Dispenzieri  3 , Leslie Amass  4 , Martin Carlsson  4 , Steve Riley  5 , Evan Powers  6 , Jeffery W Kelly  6 ; THAOS investigators
Collaborators, Affiliations

Survival in a Contemporary, Real-World Cohort of Patients with Mixed-Phenotype Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis: An Analysis from THAOS

Jonas Wixner et al. Cardiol Ther. .

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov identifier NCT00628745.

Keywords: Mixed phenotype; Real-world; Tafamidis; Transthyretin amyloid cardiomyopathy.

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Conflict of interest statement

Declarations. Conflict of Interest: Jonas Wixner reports consulting fees and travel support for lectures and advisory boards from Alnylam and Pfizer and consulting fees from Akcea, AstraZeneca, Bayer and Intellia. Angela Dispenzieri reports research grants from Alnylam, Celgene, Janssen, Millennium, and Pfizer; funding for meeting expenses (travel) from Pfizer; and attending advisory boards for Akcea and Intellia. Leslie Amass, Martin Carlsson, and Steve Riley are employees of Pfizer. Evan Powers receives royalty payments from tafamidis sales. Jeffery W Kelly receives royalty payments from tafamidis sales and reports consulting fees and travel support for lectures from Pfizer and attending advistory boards for Pfizer. Ethical Approval: All THAOS sites received ethical or institutional review board approval before patient enrollment, and all patients provided written informed consent. The ethics committee that approved the study at the lead author’s institution was Regionala etikprövningsnämnden i Umeå. All other committees are listed in Supplementary Table S1. The study followed the Good Pharmacoepidemiology Practice guidelines and the principles of the Declaration of Helsinki.

References

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