Functional Stability Measured by Changes in the 6-min Walk Test in Patients Treated with Tafamidis Versus Placebo: Post hoc Analysis from ATTR-ACT

Abstract

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. 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. 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. 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. Clinicaltrials.gov ID NCT01994889. Tafamidis is a treatment for transthyretin amyloid cardiomyopathy (ATTR-CM for short), a type of heart failure. During the 6-min walk test (6MWT for short), researchers measure how far patients can walk in 6 minutes. In this study, patients with ATTR-CM were given either tafamidis or placebo for 30 months. Patients took the 6MWT at the start and after 12 months. If the distance walked after 12 months was no more than 35 m shorter than at the start, this was called 6MWT stability. If the distance was 35 m shorter or more, this was called 6MWT progression. The researchers wanted to know how many patients had 6MWT stability or progression after 12 months. They then looked at how many patients died or had to go to hospital because of heart-related issues by the end of the 30 months in the 6MWT stability and progression subgroups. After 12 months, 64% of patients who received tafamidis had 6MWT stability compared to 53% of patients on placebo. Patients who had 6MWT stability and took tafamidis had a lower risk of dying than those with 6MWT stability who took placebo. Patients with 6MWT stability who took tafamidis had a lower risk of having to go to hospital due to heart-related issues than those with stability who took placebo. The researchers concluded that more patients taking tafamidis had 6MWT stability than those taking placebo. They also concluded that treatment with tafamidis had positive effects on patients.