022| Volume 26, ISSUE 10, SUPPLEMENT , S10, October 2020

Efficacy of Tafamidis by Baseline 6-minute Walk Test Distance in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT)

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      Tafamidis significantly reduced all-cause mortality and cardiovascular (CV)-related hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). The effect of tafamidis treatment was more pronounced in patients who were NYHA class I or II at baseline than in patients who were NYHA class III. However, NYHA class can be an imperfect measure of disease severity. The 6-minute walk test (6MWT), a measure of functional capacity, was identified as a predictor of overall survival in patients with ATTR-CM.


      Understanding the effect of tafamidis treatment in patients by functional capacity, as assessed by baseline 6MWT distance, will provide new data on measures of baseline disease severity and the efficacy of tafamidis.


      In ATTR-ACT, adult patients with ATTR-CM were randomized to tafamidis (n=264) or placebo (n=177) for 30 months. Patients with 6MWT distance <100m were excluded. In this post-hoc analysis, patients were grouped into quartiles based on 6MWT distance at baseline: Q1, <269m; Q2, ≥269m to 351m; Q3, ≥351m to 445m; Q4, ≥445m. Primary (hierarchical combination of all-cause mortality and CV-hospitalization frequency) and key secondary outcomes (change in 6MWT distance and Kansas City Cardiomyopathy Questionnaire-Overall Summary [KCCQ-OS] score at Month 30) with tafamidis compared with placebo were assessed for each 6MWT quartile.


      The improvement with tafamidis in the primary outcome (win ratio [95% CI]) was more pronounced in patients with a greater baseline 6MWT distance: Q1, 1.15 (0.71, 1.87); Q2, 1.48 (0.88, 2.49); Q3, 1.78 (0.95, 3.31); Q4, 2.56 (1.36, 4.84). Overall, all-cause mortality was higher in the shorter baseline 6MWT quartiles. Tafamidis significantly reduced the decline in 6MWT distance (LS mean difference [95% CI] from placebo) with minimal difference between quartiles: Q1, 73.4 (23.9, 122.9); Q2, 58.3 (0.4, 116.2); Q3, 78.2 (41.2, 115.2); Q4, 92.0 (49.2, 134.8). The reduction in the overall decline in KCCQ-OS score with tafamidis (vs placebo) was more pronounced in patients with greater baseline 6MWT distance (LS mean difference [95% CI]): Q1, 8.5 (-0.7, 17.7); Q2, 11.3 (-1.4, 24.0); Q3, 19.9 (10.7, 29.1); Q4, 15.1 (8.6, 21.6).


      Tafamidis reduces all-cause mortality and CV-related hospitalizations, and the decline in functional capacity and health-related quality of life, in all patients with ATTR-CM. The reduction in disease progression with tafamidis was observed across all quartiles; however, it was more pronounced in patients with a greater baseline 6MWT distance. These data highlight the importance of early diagnosis and treatment.
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