Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR‐ACT) and long‐term extension study

Abstract

Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM) in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). While ATTRACT was not designed for a dose-specific assessment, further analysis from ATTRACT and its long-term extension study (LTE) can guide determination of the optimal dose.

Tafamidis is entering the clinical arena for the treatment of transthyretin‐related cardiomyopathy: certainties and unmet needs

“…4 Although the conclusions are reasonable, there are some issues deserving further considerations. During study extension, patients in the placebo arm of ATTR-ACT were randomized to tafamidis 80 mg or 20 mg. 4 Therefore, patients were not continuously on 80 mg or 20 mg for the entire study duration (ATTR-ACT plus extension study), with a poorly predictable impact on the observed relative efficacy of the two doses. 22 Another aspect not clarified by the study is whether the 80 mg dose can anticipate the moment where survival curves begin to diverge, which in ATTR-ACT was around 18 months from the start of treatment.…”

“…22 Another aspect not clarified by the study is whether the 80 mg dose can anticipate the moment where survival curves begin to diverge, which in ATTR-ACT was around 18 months from the start of treatment. 1 The 80 mg and 20 mg dose seemed equally effective in reducing the decline in functional capacity or quality of life over time, 4 but further evidence is needed to clarify this point. Finally, this study did not explore the difference in survival between patients in New York Heart Association class I-II vs. III and its interaction with tafamidis dose.…”

“…This formulation is bioequivalent to tafamidis meglumine 4 × 20 mg capsules, 3 which was evaluated in the Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT). 1 In this issue of the Journal, Damy et al 4 address the important issue of the best tafamidis dose, analysing data from the ATTR-ACT study and its long-term extension study. To better interpret these results, we will briefly recapitulate the biological and structural characteristics of transthyretin (TTR), the pharmacodynamics and pharmacokinetics of tafamidis, and some data about tafamidis treatment for FAP.…”

“…1 In the current study, Damy et al performed a more in-depth analysis of ATTR-ACT and ATTR-ACT plus the longer-term treatment data (median 51 months). 4 The three endpoints were: (i) stabilization of plasma TTR, (ii) change in N-terminal pro-B-type natriuretic peptide (NT-proBNP), and (iii) all-cause mortality. The three conclusions are that:…”

February 2021 at a glance: focus on amyloidosis, myocarditis and cardiomyopathy

“…9 In an analysis of the long-term extension of ATTR-ACT, both tafamidis 80 mg and 20 mg reduced all-cause mortality and cardiovascular hospitalizations at 30 months compared with placebo, with the higher dose associated with better outcomes without safety issues in the long-term extension. 10 .…”