Improved long‐term survival with tafamidis treatment in patients with transthyretin amyloid cardiomyopathy and severe heart failure symptoms

Aim The value of disease‐modifying therapies (such as tafamidis) in patients with transthyretin amyloid cardiomyopathy (ATTR‐CM) and severe heart failure symptoms has been debated. This study assessed long‐term all‐cause survival in patients with New York Heart Association (NYHA) class III symptoms in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR‐ACT) long‐term extension (LTE) study. Methods and results At the baseline of ATTR‐ACT, 55/176 (31.3%) patients receiving tafamidis 80 mg and 63/177 (35.6%) receiving placebo had NYHA class III symptoms. After 30 months of treatment, patients could join an ongoing LTE study to receive open‐label tafamidis. In an interim analysis of the LTE study (August 2021), all‐cause mortality was lower among patients with NYHA class III symptoms who received continuous tafamidis in ATTR‐ACT and the LTE study (hazard ratio 0.64; 95% confidence interval 0.41–0.99; median follow‐up: 60 months), as compared with those who received placebo in ATTR‐ACT and tafamidis in the LTE study (median follow‐up: 56 months). Similar findings were observed in patients with NYHA class I/II symptoms at baseline (0.50; 0.35–0.73; tafamidis 80 mg n = 121; placebo n = 114; median follow‐up of 61 and 60 months, respectively). Conclusion We observed reduced all‐cause mortality with continuous tafamidis treatment compared with delayed tafamidis treatment (placebo then tafamidis) in patients with NYHA class III symptoms at baseline over a median follow‐up of ∼5 years. These findings demonstrate the value of tafamidis treatment in patients with ATTR‐CM and severe heart failure symptoms, and emphasize the importance of early treatment. Clinical Trial Registrations: ClinicalTrials.gov NCT01994889 and NCT02791230.