Phenotypic Considerations for Tafamidis Use in a Real-World Cohort of Older Patients with Transthyretin Amyloid Cardiomyopathy

Disease-modifying therapies for transthyretin amyloid cardiomyopathy (ATTR-CM) improve clinical outcomes, yet older patients are undertreated. In this analysis, we evaluated survival and cardiovascular-related hospitalizations (CVH) among patients treated with tafamidis (tafamidis free acid at 61 mg or bioequivalent tafamidis meglumine at 80 mg) aged < 80, 80–85, and > 85 years to assess effects of baseline clinical phenotype on outcomes. Data were pooled from an early access cohort (ClinicalTrials.gov ID: NCT02791230) and the Transthyretin Amyloidosis Outcomes Survey registry (NCT00628745; enrollment 2019–2023; cardiac/mixed phenotype). Outcomes included all-cause mortality (ACM), CVH, and ACM or CVH. Cox proportional hazards and negative binomial regression models were adjusted for age, sex, TTR genotype, phenotype, New York Heart Association (NYHA) class, and estimated glomerular filtration rate (eGFR). Among the 1924 patients enrolled in the study, 1188, 505, and 231 were aged < 80, 80–85, and > 85 years, respectively. Patients aged > 85 versus 80–85 and < 80 years had lower baseline mean eGFR (39.7 vs. 49.8 and 64.1 mL/min/1.73 m 2 , respectively) and lower modified body mass index (mBMI; 1047.1 vs. 1084.0 and 1134.3 kg g/[m 2 L]). Also, more patients aged > 85 years versus 80–85 and < 80 years were NYHA class IV (3.3% vs. 0.8% and 0.9%). Kaplan–Meier estimated survival rates were significantly lower in patients aged > 85 and 80–85 years versus those aged < 80 years at months 30 (56.3% and 66.2% vs. 77.0%) and 42 (42.9% and 57.2% vs. 70.9%). ACM risk was higher in patients aged > 85 years than in those aged < 80 years (hazard ratio 1.49, 95% confidence interval [CI] 1.11–2.01). Total annual CVH rates in patients aged > 85, 80–85, and < 80 years were 0.79, 0.65, and 0.59, respectively. CVH and ACM or CVH risks were similar across groups. Patients aged 80–85 and < 80 years with preserved mBMI, eGFR, or NYHA class I/II symptoms had similar survival rates. Across groups, patients with NYHA class III symptoms or eGFR < 45 mL/min/1.73 m 2 had similar survival rates. Patients aged ≥ 80 years who were treated with tafamidis had outcomes comparable to those of younger patients when clinical vulnerability markers were considered. These findings support individualized treatment decisions based on patient’s overall clinical profile and multidimensional assessment rather than age alone. ClinicalTrials.gov identifiers: NCT02791230, NCT00628745.