Acoramidis Shows Promise in Reducing Cardiovascular Hospitalizations and Improving Survival in ATTR-CM

A recent post-hoc analysis of the ATTRibute-CM trial, presented at the 2024 AHA Scientific Sessions, highlights the potential of acoramidis to reduce cardiovascular hospitalizations (CVH) and improve survival in transthyretin amyloid cardiomyopathy (ATTR-CM). Led by Kevin M. Alexander and colleagues, the study underscores the correlation between CVH and mortality, showing that acoramidis-treated patients who avoided CVH had significantly higher survival rates at 30 months when compared to those who had a CVH. However, as a post-hoc analysis, these findings warrant careful interpretation.

Background

ATTR-CM is a progressive disease that results in cardiac dysfunction and heart failure due to amyloid deposition. Acoramidis, a potent transthyretin stabilizer, demonstrated a 50% reduction in CVH risk compared to placebo in the primary results of ATTRibute-CM. This post-hoc analysis sought to evaluate whether avoiding CVH translated into improved survival among patients treated with acoramidis.

Using data from the ATTRibute-CM trial, researchers applied the Kaplan-Meier estimator to compare survival rates in acoramidis-treated participants with and without CVH over 30 months.

At Month 30, survival was significantly higher among acoramidis-treated participants without CVH (86.8%, 95% CI: 82.2–90.3) compared to those with CVH (62.4%, 95% CI: 52.6–70.7; p<0.0001). Patients with CVH had higher baseline NT-proBNP and lower eGFR, suggesting greater disease severity.

While these findings suggest a beneficial role for acoramidis in improving outcomes by reducing CVH, the post-hoc nature of this analysis introduces limitations. Post-hoc analyses are inherently exploratory and subject to selection bias, as they rely on predefined data that may not account for all confounding variables. Furthermore, the observed survival benefit may partly reflect differences in baseline disease severity between those who experienced CVH and those who did not.

Takeaways

This analysis reinforces the importance of CVH as a marker of disease progression and mortality in ATTR-CM. Acoramidis shows promise in mitigating these risks, but conclusions about its survival benefits require further validation through prospective studies. Clinicians should interpret these findings cautiously, balancing optimism about acoramidis’ potential with the need for robust, pre-specified evidence to confirm these results.

As ATTR-CM treatment strategies evolve, this study highlights the critical need for therapies that address both disease progression and its complications, while underscoring the importance of rigorous study design to ensure reliable and actionable conclusions.