Survival in a Contemporary, Real-World, Matched Cohort of Patients with Transthyretin Amyloid Cardiomyopathy Treated vs Not Treated with Tafamidis

INTRODUCTION: Tafamidis is approved for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) and has shown a survival benefit in the phase 3 study ATTR-ACT and in real-world settings. This analysis compared survival in a contemporary, matched, real-world cohort of patients with ATTR-CM treated with tafamidis vs untreated. METHODS: Data were pooled from an early access cohort (NCT02791230) and from patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS; NCT00628745) in 2019-2023 with a mixed or predominantly cardiac phenotype. Propensity score matching (1:1) was performed to match treated and untreated patients in the pooled sample based on baseline age, New York Heart Association class, and phenotype. Treated patients received tafamidis at the approved dose for ATTR-CM. RESULTS: A total of 283 treated and 283 untreated patients were included. Of the 283 treated patients, 85 were from the early access cohort and 198 from THAOS. All untreated patients were from THAOS. In treated vs untreated patients, mean age at enrollment was 76.9 vs 77.4 years, 89.0% vs 83.4% were male, 11.0% vs 16.6% were female, and 80.9% vs 73.1% had wild-type ATTR-CM. Estimated adjusted survival probabilities for all-cause mortality for treated vs untreated patients were 90.2% vs 76.0% at 30 months and 85.3% vs 67.5% at 42 months. Treated patients had a 74% lower risk of all-cause mortality compared with untreated patients (hazard ratio 0.26; 95% confidence interval 0.13-0.51). No new safety signals were identified. CONCLUSIONS: This matched-cohort analysis demonstrated improved survival in a contemporary, real-world cohort of patients with ATTR-CM receiving the approved dose of tafamidis compared with those untreated. These findings further extend the results of ATTR-ACT to contemporary populations of patients with ATTR-CM treated clinically with tafamidis and reinforce earlier real-world evidence supporting tafamidis use. TRIAL REGISTRATION: Clinicaltrials.gov identifiers NCT00628745 and NCT02791230.