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

Importance 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. Objective 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. Design, Setting, and Participants 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. Interventions Acoramidis hydrochloride (800 mg) or placebo twice daily for 30 months. Main Outcomes and Measures 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). Results 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). Conclusions and Relevance 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.