Clinical phenotype and prognosis of real‐world patients with wild‐type transthyretin amyloid cardiomyopathy treated with tafamidis

Aims Tafamidis reshaped the treatment paradigm in transthyretin amyloid cardiomyopathy (ATTR‐CM) based on a phase‐3 randomized controlled trial, but real‐world data on its use remain limited. This study aimed to assess in a large, contemporary, real‐world cohort of patients with wild‐type ATTR‐CM (ATTRwt‐CM) (i) the clinical phenotype of patients receiving tafamidis, and (ii) the association of tafamidis with survival using propensity‐matched observational data. Methods and results Data of patients diagnosed with ATTRwt‐CM (January 2017 to June 2023) from 19 Italian centres were analysed. A propensity score (PS) reflecting the likelihood of being treated with tafamidis for each patient was determined using four variables that were significantly different among the two groups: age, New York Heart Association (NYHA) class, National Amyloidosis Centre (NAC) stage and mineralocorticoid receptor antagonists (MRAs). The primary outcome was all‐cause mortality. The study comprised 1556 ATTRwt‐CM patients: 965 (62%) patients initiated on tafamidis by June 2023 and 591 (38%) patients never treated with disease‐modifying therapy. Tafamidis‐treated patients were older, exhibited a lower NYHA class and NAC stage, and were more often treated with MRAs compared to untreated patients. The PS‐matched cohort comprised 426 patients treated with tafamidis and 426 PS‐matched untreated patients (mean age 78.9 ± 5.0 years, 88.3% men, 12.9% in NYHA class III). Adequacy of matching was verified (standardized differences: <0.20 between groups). Over 25 months (interquartile range: 15–40), treatment with tafamidis was associated with lower rates of all‐cause mortality (hazard ratio 0.55, 95% confidence interval 0.39–0.77, p = 0.001) across the spectrum of NAC disease stages ( p ‐interaction = 0.94). Conclusions In this large, contemporary, real‐world cohort of patients with ATTRwt‐CM, predominantly in NYHA class I or II, treatment with tafamidis was consistently associated with a significantly lower risk of all‐cause mortality.