Early and continuous acoramidis therapy was associated with sustained reductions in mortality and cardiovascular hospitalizations through 54 months among patients with transthyretin amyloid cardiomyopathy, according to researchers.
In an international, multicenter open-label extension of the ATTRibute-CM randomized clinical trial, 389 patients who completed the parent study received acoramidis 800 mg twice daily and were followed through month 54, wrote lead study author Prem Soman, MD, PhD, of the University of Pittsburgh Medical Center, and colleagues. Patients with transthyretin amyloid cardiomyopathy who were originally assigned to acoramidis continued therapy (n = 263), whereas those assigned to placebo switched to acoramidis (n = 126).
Continuous acoramidis treatment was associated with a 45% lower risk of all-cause mortality compared with delayed initiation (26% vs 44%) and a 49% lower risk of cardiovascular mortality (19% vs 34%). First cardiovascular hospitalization occurred in 35% of patients receiving continuous therapy vs 57% of those who switched.
The primary outcome was time to all-cause mortality, cardiovascular mortality, and first cardiovascular hospitalization through month 54. The survival benefit was consistent across prespecified subgroups, including age, sex, race, genotype, New York Heart Association class, and disease stage, with no evidence of heterogeneity.
Biomarker and functional outcomes were evaluated as secondary measures. Continuous acoramidis treatment was associated with smaller increases in N-terminal pro–B-type natriuretic peptide levels compared with delayed initiation (40% vs 149%). Serum transthyretin levels increased by 37% with continuous therapy vs 25% after delayed initiation.
Functional capacity and health status were assessed using the Kansas City Cardiomyopathy Questionnaire overall summary score and six-minute walk distance. At month 54, questionnaire scores declined by 5% with continuous therapy vs 16% with delayed initiation. Six-minute walk distance declined by 9% vs 10%, respectively. Improvement in walk distance was observed after patients switched to acoramidis at month 30.
Safety was evaluated throughout the extension period. Treatment-emergent adverse events occurred in 94% of patients in both groups, with discontinuation due to adverse events in approximately 3% of patients. No new long-term safety concerns were identified.
The researchers noted several limitations, including the open-label design, imbalances in baseline characteristics at study entry, and concomitant use of therapies such as tafamidis, sodium-glucose cotransporter 2 inhibitors, and mineralocorticoid receptor antagonists, which may have influenced treatment effect estimates. The study was also not powered for subgroup analyses.
Delayed initiation of acoramidis was associated with stabilization in some biomarkers and functional measures, with improvement in others, although outcomes remained more favorable with continuous therapy.
“These findings support the importance of early and continuous long-term treatment with acoramidis in [transthyretin amyloid cardiomyopathy],” the researchers wrote.
Disclosures: Several researchers reported consulting fees, advisory roles, research support, or employment with pharmaceutical companies, including BridgeBio Pharma, which funded the study.
Source:JAMA Cardiology
The findings were also presented at the American College of Cardiology 75th Annual Scientific Session & Expo.
