Sex Differences in a Contemporary, Real-World Cohort of Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis

INTRODUCTION: Tafamidis improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) versus placebo. ATTR-CM has historically been considered a predominantly male disease, and women are underrepresented in prior studies. Sex-specific data in contemporary patients treated with tafamidis remain limited. METHODS: Data from two cohorts were pooled: an early-access cohort (NCT02791230) and patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS; NCT00628745) in 2019-2023. This analysis evaluated sex-related differences in clinical characteristics and all-cause mortality, adjusting for age, cohort, baseline New York Heart Association (NYHA) class, and wild-type (ATTRwt-CM) versus variant (ATTRv-CM) disease. RESULTS: Overall, 1924 patients treated with tafamidis were included (1476 from the early-access cohort and 448 from THAOS), of whom 214 (11.1%) were women. A smaller proportion of women than men had ATTRwt-CM (59.8% vs. 88.9%), whereas a greater proportion had ATTRv-CM (40.2% vs. 11.1%; p < 0.0001). Women were more frequently of African descent (23.9% vs. 7.4%; overall p < 0.001). Age at enrollment, age at symptom onset, and time from symptom onset to diagnosis were similar between sexes (p > 0.05). Women appeared more symptomatic at baseline, with a higher proportion in NYHA class III/IV (37.7% vs. 29.4%; overall p = 0.036) and classified as National Amyloidosis Centre stage II/III (68.1% vs. 47.7%; overall p = 0.023), despite similar N-terminal pro-B-type natriuretic peptide levels (p > 0.05). In adjusted analyses, women had a higher estimated glomerular filtration rate than men (β [men vs. women] = - 10.61; p < 0.001). Over a mean follow-up of 1.5 years, men had a higher risk of all-cause mortality than women (adjusted hazard ratio [men vs. women], 1.60, 95% CI 1.12-2.30). CONCLUSIONS: In this analysis of contemporary patients with ATTR-CM treated with tafamidis, women represented a small proportion of the overall population, and a greater proportion had ATTRv-CM compared with men. Although women appeared more symptomatic at presentation, men had a higher risk of all-cause mortality. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02791230 and NCT00628745.