Evolution of patient characteristics and outcomes in ATTR-CM clinical trials: A systematic review

Over the past decade, advancements in awareness, diagnosis, and new treatment options for transthyretin amyloid cardiomyopathy (ATTR-CM) have likely influenced the characteristics of patient populations enrolled in clinical trials. This systematic review aims to assess temporal trends in baseline characteristics of patients enrolled in ATTR-CM clinical trials.

Systematic literature searches were conducted on September 25, 2024, using Embase, MEDLINE, and Cochrane databases via Ovid and were supplemented by gray literature searches. Overall, 58 publications on 13 clinical trials enrolling patients with ATTR-CM during 2008-2022 were included. Baseline characteristics of participants enrolled in these trials and key clinical outcomes, including all-cause mortality were analyzed.

Key baseline characteristics - including the proportion of participants with variant ATTR-CM; New York Heart Association class; N-terminal pro-B-type natriuretic peptide and troponin levels; and estimated glomerular filtration rate - varied according to enrollment year. All-cause mortality in placebo groups at 12 months decreased from 9.0% in ATTR-ACT (2013-2015) to 6.9% in ATTRibute-CM (2019-2020), 5.6% in APOLLO-B (2019-2021), and 4.3% and 5.5% in HELIOS-B (overall and monotherapy populations, respectively; 2019-2021).

Patients enrolled in more recent clinical trials exhibited baseline characteristics consistent with less advanced ATTR-CM than earlier clinical trials. These descriptive findings are consistent with a temporal shift toward earlier identification and enrollment of patients with ATTR-CM, occurring alongside advances in diagnostic techniques and availability of disease-modifying treatments. These observations highlight the importance of evaluating the relevance of clinical outcomes and trial design in evolving patient populations and therapeutic landscapes.