Survival in a contemporary, real-world, matched cohort of patients with transthyretin amyloid cardiomyopathy treated vs not treated with tafamidis

Background Tafamidis (meglumine 80 mg/free acid 61 mg) is approved to treat transthyretin amyloid cardiomyopathy (ATTR-CM). In the pivotal phase 3 study ATTR-ACT, tafamidis significantly reduced all-cause mortality (ACM) and cardiovascular-related hospitalisations in patients with ATTR-CM (1). Real-world data further extend and support the benefit of long-term tafamidis for improving survival in contemporary patients with ATTR-CM (2). Purpose To further compare survival in a contemporary, real-world, pooled, matched cohort of patients with ATTR-CM treated vs not treated with tafamidis, adjusted for potential prognosticators of treatment effect. Methods Data were pooled from 2 studies. One study included a contemporary cohort of patients with ATTR-CM who received early access to tafamidis in the ATTR-ACT long-term extension (LTE) study but did not participate in the parent study. The other study included a contemporary cohort of patients from the Transthyretin Amyloidosis Outcomes Survey (THAOS; NCT00628745) with predominantly cardiac or mixed phenotype ATTR-CM enrolled between 2019–2023 who received tafamidis throughout the study or never received tafamidis. THAOS was a longitudinal, observational, phase 4 study of patients with transthyretin amyloidosis and asymptomatic gene carriers. Treated patients were pooled from the 2 studies; all received the approved dose of tafamidis. Untreated patients were from THAOS. A propensity score matching procedure was used to match treated and not treated patients 1:1 on 3 significant variables identified from a multivariate logistic regression analysis: baseline age, New York Heart Association (NYHA) class and phenotype (cardiac, mixed); other variables considered were sex, estimated glomerular filtration rate (eGFR), follow-up time and modified body mass index (mBMI). Results In all, 566 patients (283 treated, 283 not treated) were included; 85 treated patients were from the LTE study and 198 were from THAOS. In treated and not treated patients, respectively, median age at enrolment was 78.0 and 78.7 years, and 89.0% and 83.4% were male (Table). The estimated adjusted survival probabilities for ACM for treated vs not treated patients were 78.0% vs 67.9% at 30 months and 70.2% vs 57.9% at 42 months (Figure). The hazard ratio (HR) for time to event for ACM was 0.62 (95% CI 0.41–0.92), favouring tafamidis. Conclusions This matched-cohort analysis showed better survival in a contemporary, real-world cohort of patients with ATTR-CM receiving the approved dose of tafamidis vs those not treated. These findings further extend results of ATTR-ACT to contemporary populations of patients with ATTR-CM treated clinically with tafamidis. These data show greater effectiveness of tafamidis for ATTR-CM in clinical practice than observed in earlier clinical trials, which may reflect earlier diagnosis and treatment in contemporary patients.