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Introduction
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.
Hypothesis
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.
Methods
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.
Results
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).
Conclusions
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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© 2020 Published by Elsevier Inc.
