Wild type transthyretin amyloidosis: real-life experience of tafamidis use and frailty analysis of treated patients

Background

Tafamidis was the first treatment approved in Spain to treat wild-type transthyretin cardiac amyloidosis (TTRwtCA). However, there is limited information on its use in real-world clinical practice, especially regarding patient frailty. Cardiac amyloidosis is associated with a higher risk of mortality and hospital readmission, and presents a frailty phenotype that requires multidisciplinary care.

Purpose

The aim of this study was to describe the experience with Tafamidis 61 mg and the degree of frailty in treated patients at a regional hospital with a catchment population of 450,000.

Methods

A prospective cohort study was conducted on patients with TTRwtCA treated with Tafamidis from 01/04/2024 to 31/12/2025.

Baseline data and data at 12 months of follow-up were analyzed. Clinical variables were evaluated (left ventricular ejection fraction -LVEF-, presence of atrial fibrillation or flutter, distance covered in the six minute walk test -6MWT-), laboratory tests (Nt proBNP, glomerular filtration rate (GFR), CA125…), use of diuretics and frailty parameters (Barthel Index, Frailty Index, Profund Index).

Results

A total of 48 patients (15% women, mean age 83 years) initiated Tafamidis 61 mg, 89% were in NYHA class II and 54% had atrial fibrillation. The median results were: LVEF 56%, 6MWT 310 meters, NT-ProBNP 1946 pg/mL, CA125 14 U/mL, and GFR 50 mL/min/1.73 m². 71% of patients were treated with loop diuretics, 17% with thiazide diuretics, 88% with SGLT2 inhibitors, 33% with beta-blockers, and 35% with mineralocorticoid receptor antagonists (MRA). Regarding frailty indices, the median Barthel Index was 95, Frailty Index was 0.16, and PROFUND Index was 3.

Tafamidis was well tolerated, with definitive discontinuation required in 3 cases due to diarrhea and 1 due to drowsiness and dizziness.

Data obtained after one year of follow-up and treatment with Tafamidis in 24 patients showed that 83% were in NYHA class II and 56% had atrial fibrillation. Median results were: LVEF 53%, 6MWT 315 meters, NT-ProBNP 1924 pg/mL, CA125 11.5 U/mL, and GFR 52 mL/min/1.73 m². 69% of patients were still being treated with loop diuretics, 17% with thiazide diuretics, 96% with SGLT2 inhibitors, 23% with beta-blockers, and 35% were receiving MRA. Regarding frailty indices, the median Barthel Index was 95, Frailty Index was 0.15, and PROFUND Index was 6.

Conclusions

Our cohort of patients with TTRwtCA treated with Tafamidis presented a low frailty profile and good survival as estimated by validated scales. The drug was well tolerated, with definitive discontinuation required in 2 cases due to adverse effects. At the review after one year of tafamidis treatment, few changes were observed in the parameters analyzed at baseline, except for a worsening of the Profund Index. One of the patients died before the end of the one-year follow-up from cardiovascular causes, but not because of heart failure.