Acoramidis reduces the burden of cumulative CV events in ATTR-CM

In a post hoc exploratory analysis of ATTRibute-CM, acoramidis significantly reduced the risk of cumulative cardiovascular mortality or recurrent cardiovascular-related hospitalization in patients with ATTR-CM compared with placebo.

This summary is based on the publication of Masri M, Judge DP, Ruberg FL, et al. - Effect of Acoramidis on Recurrent and Cumulative Cardiovascular Outcomes in ATTR-CM: Exploratory Analysis From ATTRibute-CM. J Am Coll Cardiol. 2025 Sep 28:S0735-1097(25)07774-5. [Online ahead of print] doi: 10.1016/j.jacc.2025.09.013.

Introduction and methods

Background

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal disease associated with a high burden of cardiovascular morbidity and mortality, particularly recurrent cardiovascular-related hospitalizations (CVH) [1-7]. While prior analyses of the phase 3 ATTRibute-CM trial demonstrated that the TTR stabilizer acoramidis reduces the composite of all-cause mortality or first CVH [7], the effect of acoramidis on the cumulative burden of cardiovascular events has not been fully characterized.

Aim of the study

The aim of this analysis was to evaluate the effect of acoramidis on recurrent and cumulative incidence of cardiovascular outcomes from ATTRibute-CM trial and its open-label extension (OLE) study.

Methods

This post hoc exploratory analysis included 611 participants with ATTR-CM from the modified intention-to-treat population (acoramidis n=409; placebo n=202). Cumulative incidences of cardiovascular mortality and recurrent CVH were assessed through 30 months, with cardiovascular mortality additionally evaluated through 42 months in OLE. Cumulative events were estimated using a modified Andersen-Gill model. All cardiovascular events were centrally adjudicated.

Outcomes

The main outcome of this analysis was a composite of cardiovascular mortality or recurrent CVH (first and subsequent CVH). The individual components of the composite were also assessed individually (cardiovascular mortality at 42 months and recurrent CVH at 30 months).

Main results

• At 30 months, acoramidis reduced the risk of cumulative cardiovascular mortality or recurrent CVH compared with placebo (HR 0.51; 95%CI: 0.43–0.62; P<0.0001).
• Numerically fewer CV events were observed at month 1 in the acoramidis group compared with the placebo group, and this difference increased progressively through month 30.
• At 42 months, continued treatment with acoramidis was associated with a lower risk of cardiovascular mortality compared with patients who switched from placebo to acoramidis in OLE (HR: 0.55; 95%CI: 0.39-0.79; P=0.0011).
• At 30 months, acoramidis reduced the risk of recurrent CVH compared with placebo (RR: 0.50; 95%CI: 0.35-0.69; P<0.0001).

Conclusion

In this post hoc exploratory analysis of ATTRibute-CM, acoramidis significantly reduced the risk of cumulative cardiovascular mortality or CVH in patients with ATTR-CM. According to the authors, “these findings suggest that acoramidis may provide early and sustained reductions in the burden of CV outcomes, underscoring the importance of strategies for prompt treatment initiation following a diagnosis of ATTR-CM.”

Find this article online at J Am Coll Cardiol.

References

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