The plasma protein transthyretin (TTR) transports retinol-binding protein and thyroxine1.Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive cause of heart failure caused by the deposition of misfolded TTR protein as amyloid fibrils in the myocardium, leading to impaired cardiac function1. As the disease progresses, supportive care alone has limited impact, which has prompting the development of disease-modifying therapies in recent years.
The most well-established therapy is tafamidis, approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). It binds to thyroxine-binding sites on TTR, preventing tetramer dissociation and thereby inhibiting amyloid formation. Numerous post-2020 real-world trials validate that tafamidis substantially prolongs survival, decreases cardiovascular hospitalizations, and provides the maximum benefit when started early 2. Diflunisal, an off-label non-steroidal anti-inflammatory drug (NSAID), also stabilises TTR but is not commonly used because of its gastrointestinal and renal side effects. Novel gene-silencing therapies, such as patisiran and inotersen, reduce hepatic production of TTR, lowering circulating levels and preventing further amyloid deposition 3.