Effect of Tafamidis on Renal Function in Patients With Transthyretin Amyloid Cardiomyopathy in ATTR-ACT.

Background: Chronic kidney disease (CKD) is common among patients with amyloid cardiomyopathy. Tafamidis was approved for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) based on findings from ATTR-ACT (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy). Objectives: This post hoc analysis evaluated changes in renal function among patients with ATTR-CM in ATTR-ACT. Methods: Patients were randomized to receive tafamidis (20 mg and 80 mg pooled) or placebo for 30 months. The change from baseline in the estimated glomerular filtration rate (eGFR) was compared over time. A composite endpoint of all-cause death, dialysis, kidney transplant, or ≥30% decline in eGFR from baseline was analyzed based on the time to first event. Results: The mean baseline eGFR was 57.5 ± 17.3 and 55.6 ± 16.8 mL/min/1.73 m2 in the tafamidis (n = 264) and placebo (n = 177) groups, respectively. At 30 months, patients treated with tafamidis had a significantly smaller decline in eGFR compared with placebo (least squares mean difference = 3.99 mL/min/1.73 m2; 95% CI: 1.31-6.68; P = 0.004). In patients who completed ATTR-ACT, improvement in CKD staging was more common with tafamidis vs placebo treatment (17.7% vs 7.2%; OR: 2.75; 95% CI: 1.10-6.90; P = 0.034). A lower proportion of tafamidis-treated patients reached the composite renal endpoint (crude rates 34.5% vs 44.1%; HR: 0.73, 95% CI: 0.54-0.99; P = 0.040). Conclusions: Renal function deteriorates over time in patients with ATTR-CM, and tafamidis treatment was associated with a reduction in this deterioration, and a higher incidence of improved eGFR and CKD staging over 30 months compared with placebo. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT] NCT01994889).

Effect of long-term tafamidis treatment on health-related quality of life in patients with transthyretin amyloid cardiomyopathy.

AIMS: To evaluate the effect of long-term tafamidis treatment on health-related quality of life (HRQoL) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) enrolled in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension (LTE) study. METHODS AND RESULTS: We examined change from baseline in Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) and clinical summary (KCCQ-CS) scores in patients who received tafamidis meglumine 80 mg for 30 months in ATTR-ACT and tafamidis (meglumine 80 mg or bioequivalent free acid 61 mg) for 30 months in the LTE study, and in patients who received placebo for 30 months in ATTR-ACT and tafamidis for 30 months in the LTE study. In ATTR-ACT, 176 and 177 patients were randomized to tafamidis 80 mg and placebo, respectively. Patients who continuously received tafamidis had a 6- to 7-point reduction in least squares (LS) mean (standard error) KCCQ-OS and KCCQ-CS scores at month 30 (-6.25 [1.53] and -7.48 [1.39]), with little or no further decline over the next 30 months (-5.92 [1.77] and -9.21 [1.88] at month 60). Patients who received placebo in ATTR-ACT had a 20-point reduction in LS mean KCCQ-OS and KCCQ-CS scores at month 30 (-19.60 [1.94] and -19.90 [2.01]), but the decline slowed after initiating tafamidis (-24.70 [3.04] and -25.30 [3.36] at month 60). CONCLUSION: Tafamidis reduced HRQoL decline in patients with ATTR-CM. Patients continuously treated with tafamidis for 60 months demonstrated stabilized HRQoL. In patients who initially received placebo in ATTR-ACT, tafamidis reduced the decline in HRQoL during the LTE study.

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

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).