Key result
TTR stabilizers and gene silencers advance ATTR cardiac amyloidosis care, but optimal combination strategies remain undefined.
Why the study?
Despite advances in pharmacological treatments for ATTR cardiac amyloidosis, substantial knowledge gaps remain regarding head-to-head comparisons, optimal combination therapies, and the role of conventional medical therapy.
This review highlights the rapid advancement in ATTR-CA therapies, including stabilizers and gene silencers, while identifying key knowledge gaps such as the lack of head-to-head trials and undefined combination regimens.
TTR therapies advance ATTR-CA care; leaves open optimal combinations and conventional therapy role pending prospective trials.
The purpose of this review article is to discuss the current treatment modalities and ongoing clinical trials regarding cardiac amyloidosis (CA), specifically transthyretin cardiac amyloidosis (ATTR-CA). Amyloidosis refers to the extracellular deposition of insoluble amyloid fibrillar proteins. When these proteins are deposited in the heart’s myocardium, it is referred to as cardiac amyloidosis. CA can be divided into two main groups: light chain cardiac amyloidosis (AL-CA) and transthyretin cardiac amyloidosis (ATTR-CA), which can be further subdivided into wild-type transthyretin amyloidosis (ATTRwt) and hereditary transthyretin amyloidosis (ATTRv). ATTR-CA is an increasingly recognized cause of heart failure in the setting of progressive restrictive cardiomyopathy, particularly among older adults, males, and individuals of African descent, with remarkable advances in the therapeutic landscape. TTR stabilizers, including Tafamidis (approved in 2019) and Acoramidis (approved in 2024), have demonstrated significant reductions in mortality and cardiovascular hospitalizations. Gene silencing therapies, including Vutrisiran (approved in 2025), represent a new drug group that targets TTR production at the RNA level. Meanwhile, CRISPR-based gene editing with nexiguran ziclumeran (nex-z or NTLA-2001) and amyloid-depleting monoclonal antibodies offer the prospect of one-time curative treatments and active fibril clearance, respectively. However, despite these advances, substantial knowledge gaps persist: no head-to-head trials have compared stabilizers to silencers, optimal combination therapy regimens remain undefined, and the role of conventional guideline-directed medical therapy in ATTR-CA has only been supported by observational data.
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Bains et al. (2026) conducted a review in Transthyretin cardiac amyloidosis (ATTR-CA). Pharmacological management (TTR stabilizers, gene silencing therapies, CRISPR-based gene editing, monoclonal antibodies) was evaluated. TTR stabilizers and gene silencing therapies have advanced ATTR cardiac amyloidosis treatment, though optimal combination regimens and the role of conventional medical therapy remain undefined.
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