Abstract
Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a cause of heart failure with preserved ejection fraction in older adults. Tafamidis, a transthyretin stabilizer, is the first disease-modifying therapy approved for ATTR-CM. Although its efficacy was demonstrated in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) trial, real-world data are essential to evaluate its effectiveness across broader and more diverse patient populations. This review synthesizes real-world evidence on tafamidis, including patient characteristics, diagnostic and therapeutic delays, and clinical outcomes such as mortality, hospitalization, cardiac biomarker trends, imaging findings, and functional capacity. Compared with clinical trial participants, real-world patients are generally older, often present with more advanced disease, and initiate treatment later in the disease course. Nevertheless, observational studies from Japan and other countries consistently show that tafamidis is associated with improved survival, reduced heart failure hospitalizations, stabilization of cardiac structure and biomarkers, and preservation of physical function – especially when therapy is started early. Accumulating such data will be crucial for optimizing patient care, particularly in the context of future treatment strategies involving emerging agents such as a next-generation oral transthyretin stabilizer and a subcutaneously administered RNA interference therapeutic. This review aims to bridge the gap between clinical trial findings and routine practice, supporting informed decision-making in the management of this progressive and underdiagnosed condition.
