Ann Med Surg (Lond). 2026 Jun 9;88(7):4763-4764. doi: 10.1097/MS9.0000000000005215. eCollection 2026 Jul.
ABSTRACT
Transthyretin amyloid cardiomyopathy (ATTR-CM) now has three approved disease-modifying agents: tafamidis, acoramidis, and vutrisiran, representing two mechanistically distinct classes: TTR tetramer stabilizers and RNA interference (RNAi) gene silencers. The phase 3 HELIOS-B trial, published in the New England Journal of Medicine, demonstrated that vutrisiran, a subcutaneous RNAi therapeutic, reduced the composite of all-cause mortality and recurrent cardiovascular events compared with placebo (hazard ratio 0.72; P = 0.01) in 655 patients with ATTR-CM over 33-36 months. These results supported the March 2025 FDA approval of vutrisiran for this indication. This letter contextualizes the mechanistic shift from stabilization to silencing, discusses the limitations of the HELIOS-B trial design, and examines the implications of an expanding therapeutic landscape for which patient-level selection criteria remain undefined. The ongoing CARDIO-TTRansform trial of the antisense oligonucleotide eplontersen will provide further comparative data, but head-to-head evidence across existing approved agents is absent. The question of how to sequence or select between mechanistically distinct agents for individual patients represents the central unresolved issue in ATTR-CM management.
PMID:42433826 | PMC:PMC13354343 | DOI:10.1097/MS9.0000000000005215