Hellenbart Erika L, Ipema Heather J, Rodriguez-Ziccardi Mary C, Krishna Hema, DiDomenico Robert J
Department of Pharmacy Practice, University of Illinois Chicago, Chicago, Illinois, USA.
Department of Medicine, Section of Cardiology, University of Illinois Chicago, Chicago, Illinois, USA.
Pharmacotherapy. 2025 Feb;45(2):124-144. doi: 10.1002/phar.4639. Epub 2024 Dec 23.
Transthyretin amyloidosis (ATTR) is a rare disease that results in amyloid fibril misfolding and deposition in multiple organs, including the heart, leading to the development of ATTR cardiomyopathy (ATTR-CM), which is associated with poor outcomes. In the last decade, several disease-modifying medications are in advanced stages of clinical development or have been approved to treat ATTR-CM. The purpose of this review is to critically evaluate clinical trial data investigating the use of approved and investigational medications for the treatment of ATTR-CM. We performed a comprehensive literature search via PubMed and EMBASE to identify randomized controlled trials evaluating medications for the treatment of ATTR-CM published through August 2024. This narrative review describes the pathophysiology of ATTR-CM, highlights important screening and diagnostic work-up, and summarizes the existing clinical evidence resulting from our literature search. Several classes of disease-modifying medications are in development for ATTR-CM. The tetramer stabilizers and transthyretin silencers have proven to be the most effective therapies to date. Tafamidis and acoramidis are currently approved for ATTR-CM while vutrisiran approval for ATTR-CM may be forthcoming. Other disease-modifying medication classes in development include antisense oligonucleotides, gene editing therapies, and monoclonal antibodies. However, several unmet needs exist including the lack of cost-effectiveness due to the extremely high acquisition costs of these medications. Disease-modifying medications approved and in development to treat ATTR-CM offer hope for patients with this disease, but their lack of affordability is the biggest barrier to their use.
转甲状腺素蛋白淀粉样变性（ATTR）是一种罕见疾病，可导致淀粉样纤维错误折叠并沉积于包括心脏在内的多个器官，进而引发ATTR心肌病（ATTR-CM），其预后较差。在过去十年中，几种疾病修饰药物正处于临床开发的后期阶段，或已获批用于治疗ATTR-CM。本综述的目的是严格评估关于使用已获批和正在研究的药物治疗ATTR-CM的临床试验数据。我们通过PubMed和EMBASE进行了全面的文献检索，以确定截至2024年8月发表的评估治疗ATTR-CM药物的随机对照试验。这篇叙述性综述描述了ATTR-CM的病理生理学，强调了重要的筛查和诊断检查，并总结了我们文献检索所得的现有临床证据。有几类疾病修饰药物正在开发用于治疗ATTR-CM。四聚体稳定剂和转甲状腺素蛋白沉默剂已被证明是迄今为止最有效的治疗方法。塔法米迪斯和阿考米迪斯目前已获批用于治疗ATTR-CM，而维曲西泮获批用于治疗ATTR-CM可能也即将实现。其他正在开发的疾病修饰药物类别包括反义寡核苷酸、基因编辑疗法和单克隆抗体。然而，仍存在一些未满足的需求，包括由于这些药物的获取成本极高而缺乏成本效益。已获批和正在开发用于治疗ATTR-CM的疾病修饰药物为该病患者带来了希望，但它们缺乏可承受性是其应用的最大障碍。
