Abstract
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.