Acoramidis Reduced Outpatient Worsening Heart Failure in ATTR-CM: Post Hoc ATTRibute-CM Analysis

Edited by:
Jennifer J. Spector, DPM, FACFAS

Key Highlights

  • Outpatient worsening heart failure, defined as starting or increasing a loop diuretic after baseline, occurred in 47.0% of participants.
  • First outpatient worsening heart failure was less frequent with acoramidis than placebo (hazard ratio [HR], 0.59; 95% CI, 0.46-0.75).
  • After adjustment for the timing of first outpatient worsening heart failure, acoramidis remained associated with lower risks of the combined outcome of all-cause mortality and recurrent cardiovascular-related hospitalization, and of first cardiovascular-related hospitalization.

Acoramidis was associated with a lower risk of outpatient worsening heart failure than placebo in a post hoc analysis of the phase 3 ATTRibute-CM trial, according to findings presented at the Heart Failure Society of America 2026 Annual Scientific Meeting. The analysis also found that outpatient worsening heart failure was associated with subsequent clinical outcomes in participants with transthyretin amyloid cardiomyopathy (ATTR-CM).

Researchers analyzed the trial’s modified intention-to-treat population of 611 participants. They defined outpatient worsening heart failure as initiation of, or an increase in, loop diuretics after baseline. Cox regression models assessed its association with clinical outcomes through month 30, accounting for randomization factors and baseline 6-minute walk distance. The investigators also compared acoramidis with placebo and examined treatment outcomes after adjusting for first outpatient worsening heart failure as a time-dependent variable. Reported P values were nominal.

Study Findings

Outpatient worsening heart failure occurred in 287 participants (47.0%). It was associated with higher risks of the combined outcome of all-cause mortality and recurrent cardiovascular-related hospitalization (HR, 1.95; 95% CI, 1.51-2.51), first cardiovascular-related hospitalization (HR, 2.78; 95% CI, 1.95-3.95), all-cause mortality (HR, 1.64; 95% CI, 1.14-2.36), and cardiovascular-related mortality (HR, 1.63; 95% CI, 1.08-2.46). All reported comparisons had nominal P values below .05.

Outpatient worsening heart failure occurred in 167 of 409 acoramidis recipients (40.8%) and 120 of 202 placebo recipients (59.4%). Acoramidis was associated with a 41% lower risk of a first event (HR, 0.59; 95% CI, 0.46-0.75; nominal P<.0001). The abstract reports separation of the Kaplan-Meier curves by day 30.

After adjustment for first outpatient worsening heart failure as a time-dependent variable, acoramidis remained associated with lower risks of all-cause mortality and recurrent cardiovascular-related hospitalization (HR, 0.59; 95% CI, 0.45-0.77; nominal P=.0001) and first cardiovascular-related hospitalization (HR, 0.63; 95% CI, 0.45-0.88; nominal P=.0072) compared with placebo.

Clinical Implications

According to the authors, outpatient worsening heart failure was prognostic of other clinical outcomes in participants with ATTR-CM. They concluded that acoramidis reduced the risk of this event early in follow-up and remained associated with lower hospitalization-related risks after adjustment for its timing.

Reference

Fontana M, Cappelli F, Garcia-Pavia P, et al. Effect of acoramidis on outpatient worsening heart failure in transthyretin amyloid cardiomyopathy: findings from ATTRibute-CM. HFSA ePoster Library. October 11, 2026. Poster 4235183.