背景:淀粉样变性是由不溶性错误折叠蛋白的细胞外沉积引起的一组异质性疾病,导致终末器官损伤。转甲状腺素蛋白淀粉样心肌病(ATTR-CM)是一种亚型,其中称为转甲状腺素蛋白的蛋白质在心脏组织内积累,逐渐导致限制性心肌病和心力衰竭。由于ATTR-CM的渐进性,临床管理需要有效的治疗方案来控制衰弱状况,Tafamidis在这方面显示出有希望的结果.
方法:ATTR-CM由于其性质和有限的治疗选择而提出了重大挑战。Tafamidis是一种新颖的疗法,旨在稳定运甲状腺素蛋白四聚体,抑制淀粉样纤维的形成。它已成为一种有前途的治疗方法,也是唯一获得FDA批准的ATTR-CM药物。Tafamidis在减缓ATTR-CM患者的疾病进展和改善预后方面的作用已在主要的随机对照试验ATTR-ACT中得到证实,具有有希望的开放标签扩展研究。一些仍在进行中。此外,真实世界的证据支持它在临床实践中的使用,显示其在降低与这种情况相关的发病率和死亡率方面的作用。临床证据表明其在改善患者症状和心功能方面的功效。案例研究还揭示了对患者的显着益处,例如减少心肌损伤,心房颤动逆转,和心力衰竭症状的解决。真实世界的结果和临床试验显示淀粉样蛋白沉积持续减少,心血管相关的住院,以及Tafamidis治疗的全因死亡率。
结论:Tafamidis是ATTR-CM治疗的重要组成部分,本叙述性综述综合了目前有关安全性的证据,功效,以及在实际实践中的利用。虽然它显示出有希望的效果,其有效性也可能有所不同,高成本阻碍了现实世界的大规模研究。总的来说,Tafamidis成为管理ATTR-CM的有价值的治疗选择。
BACKGROUND: Amyloidosis is a heterogeneous group of disorders caused by the extracellular deposition of insoluble misfolded proteins, leading to end-organ damage. Transthyretin amyloid
cardiomyopathy (ATTR-CM) is a subtype in which a protein known as transthyretin accumulates within the heart tissue, progressively resulting in restrictive
cardiomyopathy and heart failure. Due to the progressive nature of ATTR-CM, clinical management requires efficacious regimens to manage the debilitating condition and Tafamidis shows promising results in this regard.
METHODS: ATTR-CM poses a significant challenge due to its nature and limited therapeutic options. Tafamidis is a novel therapy designed to stabilize the transthyretin tetramers, inhibiting the formation of amyloid fibrils. It has emerged as a promising treatment and the only FDA-approved drug for ATTR-CM. Tafamidis\' role in slowing disease progression and improving outcomes in patients with ATTR-CM has been demonstrated in the major randomized control trial ATTR-ACT with promising open-label extension studies, some still ongoing. Additionally, real-world evidence supports its use in clinical practice, showing its role in reducing morbidity and mortality associated with this condition. Clinical evidence shows its efficacy in improving symptoms and cardiac function in patients. Case studies also reveal significant benefits to patients like reducing myocardial damage, reversal of atrial fibrillation, and resolution of heart failure symptoms. Real-world outcomes and clinical trials show a consistent reduction in amyloid deposition, cardiovascular-related hospitalizations, and all-cause mortality with Tafamidis therapy.
CONCLUSIONS: Tafamidis is an essential component of the treatment of ATTR-CM and this narrative
review synthesizes the current evidence regarding safety, efficacy, and utilization in real practice. While it shows promising effects, its effectiveness may also vary and high cost precludes real-world large-scale studies. Overall, Tafamidis emerges as a valuable therapeutic option for managing ATTR-CM.