Conference Coverage

Tafamidis-Associated Functional Stability Predicts Lower Mortality in ATTR-CM, Post-Hoc Analysis Finds

Edited by:
Anthony Calabro, MA

Key Highlights

  • A higher proportion of patients receiving tafamidis achieved functional stability at 12 months compared with placebo (64% vs 53%).
  • Patients with 12-month functional stability receiving tafamidis had significantly lower all-cause mortality during follow-up.
  • Tafamidis reduced the risk of cardiovascular hospitalization in patients with functional decline compared with placebo.
  • Functional stability measured by 6-minute walk distance may be associated with improved outcomes in transthyretin amyloid cardiomyopathy.

Research presented at the American College of Cardiology’s Annual Scientific Session, held March 28–30, 2026, in New Orleans, LA, suggests that functional stability measured by 6-minute walk distance (6MWD) may be associated with improved outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) treated with tafamidis. A post-hoc analysis of the phase 3 Tafamidis in Transthyretin Cardiomyopathy Clinical Trial evaluated whether early functional stability predicted subsequent clinical outcomes.1

In the original trial,2 tafamidis slowed disease progression, prolonged survival, and significantly reduced the decline in 6MWD, a marker of functional capacity in patients with ATTR-CM. In the current analysis, investigators examined whether maintaining 6MWD stability during the first year of treatment was associated with subsequent reductions in mortality and cardiovascular hospitalization.

In this post-hoc analysis, patients receiving tafamidis meglumine 80 mg or placebo were categorized according to their change in 6MWD at Month 12. Functional stability was defined as a decline of 35 meters or less from baseline, whereas progression was defined as a decline greater than 35 meters. Investigators used a Cox proportional hazards model to evaluate time to all-cause mortality and a Poisson regression model to assess cardiovascular hospitalization rates from Months 12 to 30, corresponding to the end of the study.1

Study Findings

At Month 12, a greater proportion of patients receiving tafamidis maintained functional stability compared with those receiving placebo (64% vs 53%). Among patients treated with tafamidis, those with 6MWD stability at Month 12 experienced substantially lower all-cause mortality during the subsequent follow-up period. By Month 30, the incidence of all-cause mortality was 11.5% among patients receiving tafamidis with 12-month 6MWD stability compared with 34.0% among those with 6MWD progression, representing a 73% hazard reduction (HR, 0.267; 95% CI, 0.125–0.568; P = .0006).1

Among patients receiving placebo, mortality incidence was also higher among those with functional decline. All-cause mortality incidence was 27.8% among patients with stability compared with 42.9% among those with progression, corresponding to a 41% hazard reduction when comparing stability with progression (HR, 0.593; P = .0648).1

Cardiovascular hospitalization rates were also lower among patients receiving tafamidis. Annual cardiovascular hospitalization rates with placebo were 0.79 per year among patients with 6MWD stability and 1.31 per year among those with progression. In comparison, rates among patients receiving tafamidis were 0.71 per year with stability and 0.88 per year with progression. Among patients treated with tafamidis who experienced 6MWD progression, tafamidis was associated with a significant 35% reduction in cardiovascular hospitalization risk compared with placebo (risk ratio, 0.648; 95% CI, 0.542–0.776; P < .0001).1

Clinical Implications

According to the study authors, maintaining functional stability after 1 year of treatment was associated with a lower risk of all-cause mortality during the subsequent follow-up period and reduced cardiovascular hospitalization in patients with transthyretin amyloid cardiomyopathy. The findings highlight the potential importance of preserving functional capacity, as measured by 6MWD, in improving outcomes among patients receiving tafamidis. 1

Expert Commentary

“Tafamidis resulted in a higher proportion of patients with functional stability after 1 year of treatment, with a significantly lower risk of all-cause mortality during the subsequent 18 months of follow-up,” the researchers concluded. “In patients with 6MWD progression, tafamidis significantly reduced the risk of cardiovascular hospitalization, underscoring the importance of treatment in maintaining functional stability and improving outcomes for patients with worsening heart failure.”1

References

  1. Witteles R, Hanna MA, Grogan M, Marino V, Wang R, Garcia Pavia P, et al. Functional stability measured with 6MWD in patients treated with tafamidis vs placebo: post-hoc analysis from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial. Presented at: American College of Cardiology Annual Scientific Session (ACC.26); March 28–30, 2026; New Orleans, LA. https://accscientificsession.acc.org/
  2. Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016. doi:10.1056/NEJMoa1805689