In patients with transthyretin amyloid cardiomyopathy (ATTR-CM), treatment with acoramidis reduced all-cause mortality and cardiovascular disease hospitalization, compared with placebo, according to findings from the ATTRibute-CM trial presented at ESC Congress 2023. Additionally, patients saw improved functional capacity and quality of life, researchers said.

The multinational trial randomized 632 patients (2:1 ratio) with wilde-type or variant symptomatic ATTR-CM to receive either oral acoramidis (800 mg/twice daily) or placebo for 30 months. According to researchers, participants in both groups had the option of initiating open-label, commercially available tafamidis after 12 months in the study. The median age of participants was 78 years, 90% were male, 10% were variant TTR carriers and most had New York Heart Association Class II (72.0%) or Class III (17.2%) symptoms.

The primary endpoint, analyzed at 30 months, was a hierarchical analysis by the Finklestein-Schoenfeld method of all-cause mortality, cardiovascular-related hospitalization, NT-proBNP and six-minute walkding distance (6MWD). Secondary endpoints included the components of the primary endpoint, KCCQ-OS, and serum transthyretin levels.

Results showed a highly statistically significant primary hierarchical endpoint analysis, resulting in a win ratio of 1.8 (95% CI 1.4 to 2.2; p<0.0001). Researchers observed a consistent, positive treatment effect across all components of the primary endpoint analysis, including a numerical reduction in all-cause mortality, with an absolute risk reduction of 6.4%, relative risk reduction of 25%, and hazard ratio of 0.772.

Additionally, the cumulative frequency of cardiovascular-related hospitalizations was reduced by about 50% in the acoramidis group, and improvements in NT-proBNP from baseline, as well as 6MWD were greater in the acoramidis group as well.

"The trial showed that in patients with ATTR-CM, acoramidis was consistently associated with clinical benefits," said principal investigator Julian Gillmore, MD, PhD, of University College London at the Royal Free London NHS Foundation Trust, UK. "The positive treatment effect was consistent across components of the primary endpoint, amongst key clinical subgroups, and across key secondary endpoints. Acoramidis was more effective in preserving both functional capacity and quality of life, and increased circulating transthyretin levels, compared with placebo. Acoramidis has the potential to be an effective and safe alternative to tafamidis for the treatment of ATTR-CM."

Clinical Topics: Heart Failure and Cardiomyopathies

Keywords: ESC Congress, ESC23, ACC International, Amyloidosis

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