Effect of Acoramidis on Heart Failure-Related Health Status: A Secondary Analysis of the ATTRibute-CM Randomized Clinical Trial.

Authors

Charles F Sherrod, Marianna Fontana, Julian D Gillmore, Efstathios Kastritis, Joshua D Mitchell, Jan Krejci, James M Tauras, Peter van der Meer, Chris Chen, Heather Falvey, Suresh Siddhanti, Jean-François Tamby, Jonathan C Fox, Francesco Cappelli, Ahmad Masri, Pablo Garcia-Pavia, Mazen Hanna, Brett W Sperry

Published in

JAMA cardiology. Jul 29, 2026. Epub Jul 29, 2026.

Abstract

In patients with transthyretin amyloid cardiomyopathy (ATTR-CM), acoramidis achieves near-complete (≥90%) transthyretin stabilization and reduces mortality and cardiovascular-related hospitalizations; however, its effect on patient-reported health status has not been comprehensively described.
To evaluate the effect of acoramidis on heart failure (HF)-related health status as assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-OS) in patients with ATTR-CM.
ATTRibute-CM was a phase 3, multicenter, international, placebo-controlled randomized clinical trial conducted from April 2019 through May 2023. Adults with ATTR-CM were eligible for inclusion. Data were analyzed from July 2023 through November 2023.
Acoramidis hydrochloride (800 mg) or placebo twice daily for 30 months.
The prespecified secondary outcome was least-squares mean (LSM) difference in KCCQ-OS over 30 months, analyzed using a mixed-effects model for repeated measures. Post hoc analysis at month 30 included being "alive and not worse" (KCCQ-OS <5-point decrease from baseline), "alive and well" (KCCQ-OS >60 and <10-point decrease from baseline), and "alive and better" (KCCQ-OS >5-point increase from baseline).
Among 632 adults with ATTR-CM enrolled, 611 were included in the modified intention-to-treat population. Overall mean (SD) age was 77.2 (6.6) years, and 56 participants (9.2%) were female. Baseline mean (SD) KCCQ-OSs were 71.7 (19.4) and 70.5 (20.7) in the acoramidis (n = 409) and placebo (n = 202) groups, respectively. At month 30, a statistically significant, clinically meaningful treatment benefit was observed for acoramidis vs placebo (LSM difference, 9.9; 95% CI, 6.0-13.9; P < .001). At month 30 (acoramidis: 367; placebo: 188), 171 acoramidis recipients (47%) were "alive and not worse" vs 56 placebo recipients (30%) (odds ratio, 2.1; 95% CI, 1.4-3.1; P < .001; number needed to treat [NNT] = 6). More acoramidis recipients (168 [46%]) were "alive and well" vs placebo (59 [31%]) (odds ratio, 1.9; 95% CI, 1.3-2.8; P < .001; NNT = 7). Similarly, 93 acoramidis recipients (25%) were "alive and better" vs 26 placebo recipients (14%) (odds ratio, 2.1; 95% CI, 1.3-3.4; P = .002; NNT = 9).
In this secondary analysis of the ATTRibute-CM randomized clinical trial, in patients with ATTR-CM, acoramidis significantly attenuated the decline in HF-related health status compared with placebo. These results suggest meaningful patient-centered benefits and clinically relevant modification of disease trajectory with acoramidis.
ClinicalTrials.gov Identifier: NCT03860935.

PMID:
42525404
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.

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