Fontana Marianna, Berk John L, Drachman Brian, Garcia-Pavia Pablo, Hanna Mazen, Lairez Olivier, Witteles Ronald
Division of Medicine, National Amyloidosis Centre, UCL, Royal Free Hospital, London, United Kingdom (M.F.).
Amyloidosis Center, Boston University School of Medicine, MA (J.L.B.).
Circ Heart Fail. 2025 Mar 31:e012112. doi: 10.1161/CIRCHEARTFAILURE.124.012112.
The demographics of patients with transthyretin amyloidosis with cardiomyopathy have evolved over the past decade, mostly driven by improved awareness of the disease among clinicians, noninvasive imaging tools for diagnosis, and new, effective treatments. Patients are now diagnosed earlier in their disease course, and treatment is initiated in those with milder disease, leading to improved outcomes. Earlier treatment of patients with milder disease may lead to accelerated disease stabilization and greater preservation of function. In addition, identification of patients with transthyretin amyloidosis with cardiomyopathy at an earlier disease stage translates to healthier study populations at enrollment in clinical trials, with slower disease progression compared with patients in prior trials. In this context, effect sizes between active treatment and placebo arms will likely be smaller than those seen in historic trials, although it is still possible to observe clinically relevant differences. In this review, we discuss how patient characteristics have changed from the ATTR-ACT trial to the more recent APOLLO-B, ATTRibute-CM, and HELIOS-B studies. In addition, we consider how measures of the minimal clinically important difference for particular end points can assist in clinical decision-making and targeting treatment goals. Treatment goals are evolving over time with the need for evidence-based recommendations in this clinical space. Lastly, we address unmet needs and future expectations for the management of transthyretin amyloidosis with cardiomyopathy.
在过去十年中，转甲状腺素蛋白淀粉样变心肌病患者的人口统计学特征发生了变化，这主要是由于临床医生对该疾病的认识提高、用于诊断的非侵入性成像工具以及新的有效治疗方法。患者现在在疾病进程中更早被诊断出来，并且在病情较轻的患者中开始治疗，从而改善了治疗结果。对病情较轻的患者进行早期治疗可能会加速疾病稳定并更好地保留功能。此外，在疾病早期阶段识别出转甲状腺素蛋白淀粉样变心肌病患者，意味着在临床试验入组时研究人群更健康，与先前试验中的患者相比疾病进展更慢。在这种情况下，尽管仍有可能观察到临床相关差异，但活性治疗组与安慰剂组之间的效应大小可能会小于历史试验中的情况。在本综述中，我们讨论了从ATTR-ACT试验到最近的APOLLO-B、ATTRibute-CM和HELIOS-B研究，患者特征是如何变化的。此外，我们考虑了特定终点的最小临床重要差异测量如何有助于临床决策和确定治疗目标。随着在这个临床领域对循证推荐的需求，治疗目标也在不断演变。最后，我们讨论了转甲状腺素蛋白淀粉样变心肌病管理中未满足的需求和未来期望。
