Abstract
Transthyretin (TTR) amyloid cardiomyopathy occurs when stable TTR, normally a 4-protein tetramer, becomes misfolded and aggregates to form amyloid fibrils that accumulate in the heart. Progressive accumulation causes cardiomyopathy, leading to arrhythmia and heart failure. Acoramidis is a high-affinity TTR stabilizer (⩾90%) evaluated in the ATTRibute-CM clinical trial. In this podcast discussion, Dr Mathew Maurer and Dr Adam Castaño provide insights into their recent analysis of prognostic implications of acoramidis-mediated changes to serum TTR (sTTR) in 557 patients and the associated implications for all-cause mortality. For the patients included in this analysis, acoramidis fully mediated a sharp and significant early rise in sTTR levels (mean 9.1 mg/dL) by day 28, sustained through month 30. Incremental changes (+5 mg/dL) in sTTR were associated with a 31.6% lower odds of mortality through month 30. This evidence strongly supports a direct association between early, sustained sTTR increases with acoramidis treatment and survival.