Functional Stability Measured by Changes in the 6-min Walk Test in Patients Treated with Tafamidis Versus Placebo: Post hoc Analysis from ATTR-ACT
6 affiliations
- 1Stanford Amyloid Center, Division of Cardiovascular Medicine, Stanford University School of Medicine
- 2Department of Cardiology, Cleveland Clinic
- 3Mayo Clinic
- 4Department of Cardiology, UCL Institute of Cardiovascular Science
- 5Pfizer
- 6Hospital Universitario Puerta de Hierro Majadahonda, IDIPHISA, CIBERCV, and Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Abstract
Introduction Tafamidis, a transthyretin stabilizer for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM), significantly reduced the decline in 6-min walk test (6MWT) distance, a marker of functional stability, compared with placebo in the pivotal study ATTR-ACT. In this post hoc analysis, functional stability was assessed at month 12, and the subsequent impact of treatment on all-cause mortality (ACM) and cardiovascular-related hospitalization (CVH) was examined. Methods Patients alive at month 12 who received tafamidis meglumine 80 mg (n = 149) or placebo (n = 149) were categorized by month 12 changes in 6MWT distance: stability (≤ 35-m decline from baseline) or progression (> 35-m decline from baseline). ACM and CVH rates during months 12–30 were evaluated using Cox proportional hazard and Poisson regression models, respectively. Results A greater proportion of patients treated with tafamidis had 6MWT stability at month 12 (64%) vs. placebo (53%). Month 30 ACM incidence was 12% and 34% with 6MWT stability and progression, respectively, in the tafamidis group and 28% and 43%, respectively, in the placebo group. Among patients with 6MWT stability, tafamidis resulted in a 65% hazard reduction for ACM vs. placebo (hazard ratio 0.347 [95% CI 0.166–0.724]; p = 0.0048). Model-adjusted annual CVH rates with tafamidis were numerically lower vs. placebo (6MWT stability: 0.65 vs. 0.96; 6MWT progression: 1.19 vs. 1.59). A 32% reduction in CVH risk was observed with tafamidis vs. placebo (risk ratio 0.677 [0.500–0.916]; p = 0.0115) with 6MWT stability. Conclusions Tafamidis resulted in a larger proportion of patients with functional stability after 12 months of treatment, with a significantly lower risk of ACM and CVH in patients with 6MWT stability during the subsequent 18 months. This post hoc analysis suggests treatment with tafamidis plays an important role in maintaining functional stability and improving outcomes for patients with ATTR-CM. Graphical abstract available for this article. Trial Registration Clinicaltrials.gov ID NCT01994889. Graphical Abstract
Related
- Neurologic Stability During Tafamidis Treatment in Transthyretin Amyloidosis with a Mixed Phenotype: A Multicenter Real-World Study.
- Survival in a Contemporary, Real-World, Matched Cohort of Patients with Transthyretin Amyloid Cardiomyopathy Treated vs Not Treated with Tafamidis
- Impact of Tafamidis on Transthyretin Concentration and Its Relation to All-Cause Mortality in Patients with Transthyretin Amyloid Cardiomyopathy: An Analysis from ATTR-ACT
- Cardiovascular-Related Mortality and Hospitalizations in Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis: A Post Hoc Analysis of the Phase 3 ATTR-ACT and Long-Term Extension
- Sex Differences in a Contemporary, Real-World Cohort of Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis
BibTeX
@article{witteles2026functional,
title = {{Functional Stability Measured by Changes in the 6-min Walk Test in Patients Treated with Tafamidis Versus Placebo: Post hoc Analysis from ATTR-ACT}},
author = {Ronald Witteles and Mazen A. Hanna and Martha Grogan and Perry Elliott and Ronnie Wang and Pablo Garcia-Pavia},
journal = {Cardiology and Therapy},
year = {2026},
month = aug,
doi = {10.1007/s40119-026-00471-7},
url = {https://doi.org/10.1007/s40119-026-00471-7},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Functional Stability Measured by Changes in the 6-min Walk Test in Patients Treated with Tafamidis Versus Placebo: Post hoc Analysis from ATTR-ACT
AU - Ronald Witteles
AU - Mazen A. Hanna
AU - Martha Grogan
AU - Perry Elliott
AU - Ronnie Wang
AU - Pablo Garcia-Pavia
PY - 2026
DA - 2026/08/01
JO - Cardiology and Therapy
DO - 10.1007/s40119-026-00471-7
UR - https://doi.org/10.1007/s40119-026-00471-7
AB - Introduction Tafamidis, a transthyretin stabilizer for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM), significantly reduced the decline in 6-min walk test (6MWT) distance, a marker of functional stability, compared with placebo in the pivotal study ATTR-ACT. In this post hoc analysis, functional stability was assessed at month 12, and the subsequent impact of treatment on all-cause mortality (ACM) and cardiovascular-related hospitalization (CVH) was examined. Methods Patients alive at month 12 who received tafamidis meglumine 80 mg (n = 149) or placebo (n = 149) were categorized by month 12 changes in 6MWT distance: stability (≤ 35-m decline from baseline) or progression (> 35-m decline from baseline). ACM and CVH rates during months 12–30 were evaluated using Cox proportional hazard and Poisson regression models, respectively. Results A greater proportion of patients treated with tafamidis had 6MWT stability at month 12 (64%) vs. placebo (53%). Month 30 ACM incidence was 12% and 34% with 6MWT stability and progression, respectively, in the tafamidis group and 28% and 43%, respectively, in the placebo group. Among patients with 6MWT stability, tafamidis resulted in a 65% hazard reduction for ACM vs. placebo (hazard ratio 0.347 [95% CI 0.166–0.724]; p = 0.0048). Model-adjusted annual CVH rates with tafamidis were numerically lower vs. placebo (6MWT stability: 0.65 vs. 0.96; 6MWT progression: 1.19 vs. 1.59). A 32% reduction in CVH risk was observed with tafamidis vs. placebo (risk ratio 0.677 [0.500–0.916]; p = 0.0115) with 6MWT stability. Conclusions Tafamidis resulted in a larger proportion of patients with functional stability after 12 months of treatment, with a significantly lower risk of ACM and CVH in patients with 6MWT stability during the subsequent 18 months. This post hoc analysis suggests treatment with tafamidis plays an important role in maintaining functional stability and improving outcomes for patients with ATTR-CM. Graphical abstract available for this article. Trial Registration Clinicaltrials.gov ID NCT01994889. Graphical Abstract
SN - 2193-8261
SN - 2193-6544
ER -