Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM

• Published in: Journal of clinical medicine 2024-09, Vol.13 (17), p.5291
• Main Authors: Dobner, Stephan, Zarro, Sara, Wieser, Fabian, Kassar, Mohammad, Alaour, Bashir, Wiedemann, Sebastian, Bakula, Adam, Caobelli, Federico, Stortecky, Stefan, Gräni, Christoph, Hunziker, Lukas, Bernhard, Benedikt
• Format: Article
• Language: English
• Subjects: Amyloidosis; Biopsy; Heart failure; Hospitalization; Insurance coverage; Mortality; Scintigraphy; Statistical analysis
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm13175291

: Tafamidis reduces cardiovascular morbidity and mortality in transthyretin amyloid cardiomyopathy (ATTR-CM), yet availability and access to therapy vary. : To determine how availability and access to tafamidis impact time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in ATTR-CM. : Ninety-one consecutive ATTR-CM (~97% wt-TTR) patients diagnosed between June 2019 and June 2021 were evaluated for tafamidis. Access to therapy was regulated by compassionate use [n(CU) = 42] prior to, and insurance [n(IA) = 49] after regulatory approval. : Tafamidis was started in 37/42 (88.1%), and 39/49 (79.6%) patients, respectively. At diagnosis, ATTR-CM disease stage (≤stage 2: 88.2% vs. 90.9%, = 0.92) was similar between groups. Timely access (after tafamidis approval) reduced the median time from first presentation to diagnosis from 6.2 (IQR: 1.3-28.9) to 2.4 (0.7-21.7) months, and from first presentation to therapy from 24.4 (10.7-46.8) to 11.8 (6.4-32.4) months. While RV function significantly worsened between diagnosis and therapy initiation in CU patients diagnosed before tafamidis approval (S'-velocity 10.0 ± 2.2 to 9.2 ± 2.2 cm/s; = 0.018; TAPSE 17.3 ± 4.7 to 15.7 ± 3.9 mm, = 0.008), it remained unchanged in IA patients (S'-velocity 9.6 ± 2.6 to 9.4 ± 2.3 cm/s; = 0.83; TAPSE 15.6 ± 4.2 to 16.3 ± 3.1 mm, = 0.45). After a median follow-up of 42.3 and 24.9 months in CU and IA patients, respectively, timely availability was associated with a reduction in annual heart failure hospitalizations (0.40 vs. 0.16 per patient, < 0.001) and improved MACE-free survival (HR = 0.51; 95%CI: 0.26-1.00; = 0.051). Timely diagnosis (