ATTR amyloid cardiomyopathy therapy reference (2026)

Transthyretin amyloidosis therapy in 2026 organises around two main presentations and three mechanism classes.

Cardiac amyloidosis (ATTR-CM): TTR stabilisers (tafamidis, acoramidis) bind TTR and prevent the dissociation that leads to amyloid formation. TTR silencers reduce hepatic TTR production via siRNA or ASO mechanisms; vutrisiran has ATTR-CM approval (March 2025), eplontersen carries ATTR-PN approval with cardiac data pending CARDIO-TTRansform, and patisiran is ATTR-PN-only (FDA rejected its ATTR-CM application in October 2023). Stabilisers and the cardiac-approved silencer class have outcome-positive trial data in ATTR-CM.

Polyneuropathy (hATTR-PN): TTR silencers (patisiran, vutrisiran, inotersen, eplontersen) are first-line. TTR stabilisers are options in selected populations.

Emerging tier: CRISPR-based one-time TTR knock-out programs (NTLA-2001 / nexiguran ziclumeran) are reaching pivotal data with the proposition of a single intervention replacing chronic therapy.

The diagnostic-pathway question matters. ATTR-CM has historically been underdiagnosed; bone scintigraphy, monoclonal protein workup, and genetic testing for hereditary forms are the standard workup. Diagnostic awareness in heart failure clinics and amyloid centres is the addressable-population enabler.