Advancements in pharmacological therapy for transthyretin cardiac amyloidosis and its comorbidities / 中国药房

ABSTRACT

Transthyretin cardiac amyloidosis myocardiopathy （ATTR-CM） is an infiltrative cardiomyopathy characterized by the deposition of amyloidogenic material in the myocardial interstitium due to the misfolding of monomers following the dissociation of unstable transthyretin （TTR） tetramers. Previous treatments for ATTR-CM lacked specificity，primarily targeting symptomatic management of heart failure and arrhythmias. In recent years，researchers have developed two major classes of drugs addressing the pathogenesis of ATTR-CM. The first class stabilizes TTR tetramer structure （such as tafamidis and acoramidis）， while the second class interferes with TTR synthesis （such as patisiran）. Among these，tafamidis has been confirmed as the only currently effective treatment for ATTR-CM，while other drugs are still in clinical trial stages with limited clinical evidence. Concerning the management of comorbidities in ATTR-CM，treatment mainly focuses on common cardiac comorbidities （such as heart failure and arrhythmias）. Traditional drugs used to improve heart failure prognosis （such as β-blockers and renin-angiotensin- receptor blocker），have not demonstrated prognosis improvement in ATTR-CM patients and may even lead to adverse reactions. For ATTR-CM patients with concurrent atrial fibrillation，anticoagulation therapy is recommended to prevent thrombus formation，and amiodarone can be used for rhythm control. Despite significant advancements in pharmaceutical treatments for ATTR-CM，the overall prognosis remains poor，necessitating further research into the pathogenesis and target development to enhance the prognosis of ATTR-CM patients.