Functional Capacity, Health-related Quality-of-life and Cardiac Biomarker Improvement with Tafamidis in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT)

Abstract

Introduction In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis significantly reduced all-cause mortality and cardiovascular-related hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Tafamidis inhibits formation of amyloid and may result in improvement of additional endpoints associated with disease stage. Hypothesis Patients with ATTR-CM treated with tafamidis are more likely to show improvement in functional capacity, health related quality-of-life and cardiac biomarkers compared with patients treated with placebo. Methods In ATTR-ACT, 441 adult patients with ATTR-CM (variant or wild-type) were randomized (2:1:2) to tafamidis 80 mg, tafamidis 20 mg, or placebo for 30 months, with pooled tafamidis (80mg and 20mg; n = 264) compared with placebo (n = 177). In this post-hoc analysis, change from baseline to Month 30 was assessed to determine the proportion of patients who improved in: 6-minute walk test distance (6MWT); Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score; Patient Global Assessment (PGA); NYHA class; and NT-proBNP concentration. Results In total, 33.5% of tafamidis-treated patients had an improved 6MWT distance, compared with 12.9% of placebo-treated patients. KCCQ-OS score improved in 41.8% of patients treated with tafamidis compared with 21.4% with placebo. As reported on the PGA, a greater proportion of patients were ‘very much improved’, ‘much improved’, or ‘minimally improved’ with tafamidis (42.3%) compared with placebo (23.8%). For patients with baseline NYHA Class II, 8.2% of tafamidis-treated patients and 3.7% of placebo-treated patients improved to Class I. There was a greater proportion of patients whose NT-proBNP concentration decreased with tafamidis (37.6%) compared with placebo (12.5%). Conclusions ATTR-CM is a progressive disease for which either stabilization or improvement indicates an efficacious treatment. In ATTR-ACT over one-third of patients at Month 30 had improvements in measures of functional capacity, health-related quality of life, and cardiac biomarkers. These data provide evidence of clinical improvement for patients with ATTR-CM treated with tafamidis, in addition to the benefits in survival and reduced cardiovascular hospitalization.