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. 2025 Apr;7(3):282-293.
doi: 10.1016/j.jaccao.2024.12.005. Epub 2025 Feb 11.

A Multicenter Study of Contemporary Long-Term Tafamidis Outcomes in Transthyretin Amyloid Cardiomyopathy

Ahmad Masri  1 , Priyanka Bhattacharya  2 , Brent Medoff  3 , Ain U Ejaz  4 , Miriam R Elman  5 , Pranav Chandrashekar  5 , Lauren Ives  6 , Alfonsina Mirabal Santos  2 , Sergio L Teruya  2 , Yuanzi Zhao  5 , Shuaiqi Huang  7 , Xiaofeng Wang  7 , Brett W Sperry  4 , Mathew S Maurer  2 , Prem Soman  3 , Mazen Hanna  6
Affiliations

A Multicenter Study of Contemporary Long-Term Tafamidis Outcomes in Transthyretin Amyloid Cardiomyopathy

Ahmad Masri et al. JACC CardioOncol. 2025 Apr.

Abstract

Background: Tafamidis improved survival and decreased cardiovascular hospitalizations in the ATTR-ACT trial. Due to improved recognition and earlier diagnosis, the epidemiology of transthyretin amyloid cardiomyopathy (ATTR-CM) is rapidly evolving.

Objectives: The authors sought to evaluate the contemporary long-term outcomes of patients with ATTR-CM treated with tafamidis.

Methods: Patients with ATTR-CM who received at least 1 dose of tafamidis between 2018 and 2021 at 5 amyloidosis centers in the United States were enrolled. Primary outcome was all-cause mortality.

Results: Among 624 patients, mean age was 76.9 ± 8.4 years, 12.5% were female, 17.5% were Black, and 17.5% had variant ATTR-CM. At the time of tafamidis start, 52% had NYHA functional class II, 34% had NYHA functional class III, 40% were in National Amyloidosis Center (NAC) Stage ≥II, 38% were in Columbia Stage ≥II, and the median NT-proBNP level was 1,914 (Q1-Q3: 957-3914) pg/mL. Over a median follow-up of 43.2 months (Q1-Q3: 25.2-52.8 months), 241 patients (38.6%) died. The probability of freedom from death at 65 months was 54.1% (95% CI: 47.4%-60.4%). Similarly, restricting the cohort to patients who received tafamidis within 6 months of their ATTR-CM diagnosis (n = 397, 63.6%) showed similar results, with a survival probability of 49.6% (95% CI: 37.6%-60.5%) at 65 months.

Conclusions: In a contemporary cohort of tafamidis-treated patients with ATTR-CM, 39% of patients died over a median of 43 months. Further work is needed to improve our understanding of ATTR-CM, its natural history, and how to further improve survival and prevent progression of heart failure.

Keywords: ATTR cardiomyopathy; amyloidosis; epidemiology; outcomes; tafamidis.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Masri has received research grants from Pfizer, Ionis, Attralus, and Cytokinetics and consulting fees from Cytokinetics, BMS, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, Akros, Prothena, BioMarin, AstraZeneca, and Tenaya. Dr Maurer has received grant support from NIH R01HL139671, R01AG081582-01 and grants and personal fees from Alnylam, Pfizer, Eidos, Prothena, and Ionis; and personal fees from AstraZeneca, Akcea, Intellia, and Novo-Nordisk. Dr Hanna has served on advisory boards for Pfizer, Alnylam, Ionis, Eidos, and Alexion Pharmaceuticals. Dr Soman has received institutional grant funding from Pfizer and personal consulting fees/ advisory fees from Eidos, Alnylam, and Pfizer. Dr Sperry has served on advisory boards for Alnylam, BridgeBio, and AstraZeneca and as a speaker for Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

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Graphical abstract
Figure 1
Figure 1
Survival of 624 Tafamidis-Treated Patients in the Current Study Over a median follow-up of 43.2 months (Q1-Q3: 25.2-52.8 months), 241 patients (38.6%) died. Tafamidis use was associated with a survival probability of 54.1% (95% CI: 47.4%-60.4%) at 65 months.
Figure 2
Figure 2
Survival Probability at 65 Months on Tafamidis in Subgroups (A) NYHA functional class I, II, III, and IV were associated with survival probability at 65 months of 83.0% (95% CI: 72.1%-89.9%) , 62.0% (95% CI: 55.4%-67.9%), 33.2% (95% CI: 20.4%-46.5%), and 0.0% (95% CI: 0.0%-0.0%), respectively; P < 0.001. (B) National Amyloidosis Center (NAC) Stage I, II, III, and missing were associated with survival probability at 65 months of 74% (95% CI: 67.7%-79.3%), 46.3% (95% CI: 37.6%-54.5%), 0.0% (95% CI: 0.0%-0.0%), and 53.9% (95% CI: 39.3%-66.5%), respectively; P < 0.001. Survival probability of NAC Stage III at 62 months was 18.1% (95% CI: 9.9%-28.2%). (2) Columbia Stage I, II, III, and missing were associated with survival probability at 65 months of 79.3% (95% CI: 71.5%-85.1%), 44.7% (95% CI: 37.4%-51.8%), 0.0% (95% CI: 0.0%-0.0%), and 57.4% (95% CI: 46.3%-66.9%), respectively; P < 0.001. Survival probability of Columbia Stage III at 62 months was 16.9% (95% CI: 8.4%-27.9%). (D) Variant and wild-type transthyretin amyloid cardiomyopathy were associated with survival probability of 54.9% (95% CI: 47.4%-61.8%) and 52.4% (95% CI: 42.0%-61.7%), respectively; P = 0.066.
Figure 2
Figure 2
Survival Probability at 65 Months on Tafamidis in Subgroups (A) NYHA functional class I, II, III, and IV were associated with survival probability at 65 months of 83.0% (95% CI: 72.1%-89.9%) , 62.0% (95% CI: 55.4%-67.9%), 33.2% (95% CI: 20.4%-46.5%), and 0.0% (95% CI: 0.0%-0.0%), respectively; P < 0.001. (B) National Amyloidosis Center (NAC) Stage I, II, III, and missing were associated with survival probability at 65 months of 74% (95% CI: 67.7%-79.3%), 46.3% (95% CI: 37.6%-54.5%), 0.0% (95% CI: 0.0%-0.0%), and 53.9% (95% CI: 39.3%-66.5%), respectively; P < 0.001. Survival probability of NAC Stage III at 62 months was 18.1% (95% CI: 9.9%-28.2%). (2) Columbia Stage I, II, III, and missing were associated with survival probability at 65 months of 79.3% (95% CI: 71.5%-85.1%), 44.7% (95% CI: 37.4%-51.8%), 0.0% (95% CI: 0.0%-0.0%), and 57.4% (95% CI: 46.3%-66.9%), respectively; P < 0.001. Survival probability of Columbia Stage III at 62 months was 16.9% (95% CI: 8.4%-27.9%). (D) Variant and wild-type transthyretin amyloid cardiomyopathy were associated with survival probability of 54.9% (95% CI: 47.4%-61.8%) and 52.4% (95% CI: 42.0%-61.7%), respectively; P = 0.066.
Figure 3
Figure 3
Survival Probability Sensitivity Analyses in Patients Receiving Tafamidis (A) By year of starting tafamidis (2018 to 2021) and (B) survival probability in patients who were started on tafamidis within 6 months of their transthyretin amyloid cardiomyopathy diagnosis.
Central Illustration
Central Illustration
Contemporary Long-Term Tafamidis Outcomes in Transthyretin Amyloid Cardiomyopathy In this study, 624 tafamidis-treated patients with transthyretin amyloid cardiomyopathy (ATTR-CM) were enrolled from 5 centers in the United States between 2018 and 2021, and were followed up for the primary outcome of all-cause mortality. Over a median follow-up of 43.2 months (Q1-Q3: 25.2-52.8 months), 241 patients (38.6%) died, with a survival probability of 54.1% (95% CI: 47.4%-60.4%) at 65 months (A). The survival probability varied according to NYHA functional class (B), National Amyloidosis Center (NAC) stage (C), and Columbia stage (D). vATTR = variant transthyretin amyloid cardiomyopathy.
Figure 4
Figure 4
Nonstatistical Comparison of All-Cause Mortality in the Current Cohort and Contemporary ATTR-CM Clinical Trials Current real-world survival on tafamidis (purple) is compared with the ATTR-ACT (Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy trial) pooled tafamidis (light blue with transition to dark blue at the time of transition to open-label tafamidis in the long-term extension study of ATTR-ACT), ATTR-ACT placebo (navy with transition to purple at the time of transition to open-label tafamidis in the long-term extension study of ATTR-ACT), ATTRibute-CM (Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy) acoramidis (orange), ATTRibute-CM placebo (red), HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy) vutrisiran (light green), and HELIOS-B placebo (dark green). ATTR-CM = transthyretin amyloid cardiomyopathy.
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