In the phase 3 ATTRibute-CM (Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy) trial, whose results were published in the New England Journal of Medicine,¹ acoramidis was compared with placebo in patients with symptomatic transthyretin (TTR) cardiac amyloidosis. Acoramidis was found to have benefits in all-cause mortality, cardiovascular (CV)–related hospitalizations, N-terminal pro–B-type natriuretic peptide level, and 6-min walk distance (6MWD). Acoramidis is a more potent tetramer stabilizer than is tafamidis,² which is the only approved therapy at present. There was a 25% mortality rate in untreated patients in the trial at 30 months, with maximum benefit derived by symptomatic patients with New York Heart Association (NYHA) class I or II heart failure (HF). Treatment with acoramidis was associated with: 1) significant reduction in CV-related hospitalizations by 50% over 30 months; 2) significant attenuation in decline of 6MWD; and 3) a low number needed to treat of 7 to prevent the composite endpoint of all-cause mortality and CV-related hospitalization.

Intervention at earlier stages of symptomology can offer profound composite benefits. The results of the ATTRibute-CM and ATTR-ACT (Transthyretin Amyloidosis Cardiomyopathy Clinical Trial) trials indicate that patients not receiving TTR-stabilizing therapy or those presenting with more advanced symptomology (NYHA class III or greater HF symptoms) are far more likely to be at risk of HF hospitalizations, death, and functional decline than are those receiving TTR-stabilizing therapy or those who present with NYHA class I or II HF symptoms.

The onus is on the cardiology community to develop proactive strategies to screen for patients >55 years of age with some or all risk factors, including unexplained moderate to severe left ventricular hypertrophy with diastolic dysfunction, peripheral neuropathies, autonomic dysfunction, bilateral carpal tunnel syndrome, or spinal stenosis, to name some of the most common clinical findings. Use of modern technology and electronic health records to collate these clinical and echocardiographic variables may improve screening on a system-wide level, and cascade testing of patients with hereditary variants may allow for family members to have close follow-up and observation for development of disease phenotypes.

References

1. Gillmore JD, Judge DP, Cappelli F, et al.; ATTRibute-CM Investigators. Efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy. N Engl J Med 2024;390:132-42.
2. Maurer MS, Schwartz JH, Gundapaneni B, et al.; ATTR-ACT Study Investigators. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med 2018;379:1007-16.