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

Background: Tafamidis reduces cardiovascular morbidity and mortality in transthyretin amyloid cardiomyopathy (ATTR-CM), yet availability and access to therapy vary. Objective: To determine how availability and access to tafamidis impact time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in ATTR-CM. Methods and Results: 91 consecutive ATTR-CM 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%, p= 0.92) was similar between groups. Timely access (after tafamidis approval) reduced time-from-first-presentation-to-diagnosis from median 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±2.2cm/s; p=0.018; TAPSE 17.3±4.7 to 15.7±3.9mm, p=0.008), it remained unchanged in IA patients (S’-velocity 9.6±2.6 to 9.4±2.3cm/s; p=0.83; TAPSE 15.6±4.2 to 16.3±3.1mm, p=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 of annual heart failure hospitalizations (0.40 vs. 0.16 per patient, p<0.001) and improved MACE-free survival (HR=0.51; 95%CI: 0.26-1.00; p=0.051). Timely diagnosis (<12-months) prolonged MACE-free survival (HR=0.424; 95%CI:0.22-0.81; p=0.004), and reduced HFH (HR=0.40; 95%CI:0.19-0.81); p=0.011) and all-cause mortality (HR=0.29; 95%CI:0.11-0.74); p=0.009). Conclusions: Availability of tafamidis improves diagnostic efficacy in ATTR-CM patients. Timely diagnosis and initiation of therapy reduces adverse cardiovascular events.