Transthyretin Amyloid Cardiomyopathy: Contemporary Pharmacological Management

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive infiltrative cardiomyopathy increasingly recognised as a cause of heart failure. Advances in the understanding of its pathophysiology have enabled the development of targeted therapies, making ATTR-CM a paradigm of precision medicine in cardiology. Currently approved disease-modifying therapies, including two stabilisers (tafamidis and acoramidis) and one gene-silencing agent (vutrisiran), slow disease progression and reduce hospitalisations and mortality, particularly when initiated early. Because these therapies do not reverse established amyloid deposition, supportive management remains a critical component of care and presents distinct challenges. These include universal anticoagulation in AF, careful diuretic management, the benefits of sodium–glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists, and limited tolerance to other foundational heart failure therapies. On-going intensive research is expanding the therapeutic landscape, with several Phase III trials evaluating next-generation silencers, gene-editing strategies and amyloid-removal therapies. While these advances hold promise for disease reversal and prevention, important unresolved issues arise, including optimal treatment selection, monitoring strategies and economic sustainability.