Advances in Diagnosis and Treatment Linked to Better Baseline Risk Profiles in ATTR-CM Trials

A systematic review presented at the 2024 AHA Scientific Sessions highlights how advancements in diagnostic tools and treatments for transthyretin amyloid cardiomyopathy (ATTR-CM) have improved the baseline risk profiles of patients participating in clinical trials. Led by Ahmad Masri and colleagues, this study underscores the evolution of patient characteristics over time, reflecting earlier diagnosis and improved prognosis.

Background

ATTR-CM affects approximately 120,000 adults in the United States but remains underdiagnosed. Innovations in diagnostic techniques and the availability of disease-modifying therapies have increased awareness and detection of this progressive condition. The researchers sought to evaluate temporal trends in baseline risks of patients enrolled in clinical trials for ATTR-CM.

Methods

The review analyzed 39 publications from eight clinical trials, including randomized and single-arm studies, conducted between 2008 and 2021. Data sources included Embase, MEDLINE, CENTRAL, and conference abstracts. The baseline characteristics of patients, particularly those in placebo arms, were compared across studies to assess changes over time.

Results

Several notable trends emerged:

• Recent trials (e.g., ATTRibute-CM, APOLLO-B) enrolled patients with lower NT-proBNP levels (median 1911–3178 pg/mL) and higher eGFR levels (mean 54.7–69.0 mL/min/1.73 m²), suggesting less advanced disease at enrollment.
• The proportion of patients with New York Heart Association (NYHA) Class III symptoms decreased in more recent trials, indicating earlier-stage disease in trial populations.
• All-cause mortality (ACM) rates in placebo groups declined markedly, from 9% at 12 months in the ATTR-ACT trial (2013–2015) to 5.6% in APOLLO-B (2019–2021). At 30 months, ACM rates dropped from 42.9% in ATTR-ACT to 25.7% in ATTRibute-CM.

Takeaways

This review highlights how advances in ATTR-CM diagnostics and therapies have enabled earlier identification and treatment, resulting in improved baseline health among clinical trial participants. These changes underscore the need for cautious interpretation of results when comparing older and newer trials, as differences in patient populations may impact outcomes.

By shedding light on evolving baseline risk, this study emphasizes the transformative role of improved diagnostic and therapeutic strategies in the management of ATTR-CM, ultimately contributing to better patient outcomes. Continued emphasis on early disease recognition is essential.