Improvements in Efficacy Measures With Tafamidis in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial.

ABSTRACT

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a fatal disease. Tafamidis was approved to treat patients with ATTR-CM based on findings from the ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial). Objectives: This post hoc analysis examined the proportion of patients who experienced improved efficacy measures through 30 months of treatment with tafamidis or placebo in ATTR-ACT. Methods: Patients with ATTR-CM were randomized to tafamidis (80 mg or 20 mg) or placebo. Change from baseline in 6-minute walk test distance, Kansas City Cardiomyopathy Questionnaire Overall Summary score, N-terminal pro-B-type natriuretic peptide concentration, patient global assessment of overall health, and New York Heart Association functional class were assessed at regular time points. The proportion of patients with improvement was summarized for each time point with odds ratio. Missing data were imputed as deterioration. Results: Higher proportions of tafamidis-treated patients (n = 264) than placebo-treated patients (n = 177) showed improvement in all assessments. The odds ratio for improvement favored tafamidis for all measures and at all time points. It was significant (P < 0.001) at month 30 for 6-minute walk test distance (4.9; 95% CI 2.28-10.69), Kansas City Cardiomyopathy Questionnaire Overall Summary score (3.3; 95% CI 1.85-5.78), N-terminal pro-B-type natriuretic peptide concentration (5.3; 95% CI 2.66-10.73), and patient global assessment of overall health (2.9; 95% CI 1.69-4.95). Conclusions: This analysis found that higher proportions of patients treated with tafamidis experienced improvement from baseline in measures of heart failure, functional capacity, and health-related quality of life than those treated with placebo during ATTR-ACT. These data provide further evidence of the clinical benefits of tafamidis in patients with ATTR-CM. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT]; NCT01994889).