Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) frequently develop worsening heart failure (HF) symptoms that require outpatient treatment intensification. A post hoc exploratory analysis of the phase 3 ATTRibute-CM trial evaluated associations between outpatient worsening HF and clinical outcomes and assessed the effect of acoramidis on worsening HF events. The findings were published in the European Journal of Heart Failure.

The analysis included participants from the modified intention-to-treat population of ATTRibute-CM. Outpatient worsening HF was defined as initiation or escalation of oral loop diuretics. Clinical outcomes were evaluated through 30 months of follow-up.

Findings

• Among 611 participants, 287 (47.0%) experienced outpatient worsening HF during follow-up.
• Outpatient worsening HF was associated with a higher risk of the composite of all-cause mortality and recurrent cardiovascular hospitalization (HR, 1.95; 95% CI, 1.51-2.51).
• Risks of first cardiovascular hospitalization (HR, 2.78; 95% CI, 1.95-3.95), all-cause mortality (HR, 1.64; 95% CI, 1.14-2.36), and cardiovascular mortality (HR, 1.63; 95% CI, 1.08-2.46) were also higher among participants with outpatient worsening HF.
• Acoramidis reduced the risk of first outpatient worsening HF by 41% versus placebo (HR, 0.59; 95% CI, 0.46-0.75).
• Kaplan-Meier curves separated early, with nominal statistical significance reached by day 30 (HR, 0.562; 95% CI, 0.317-0.998; p=0.0492) and maintained from day 134 through month 30.
• After adjustment for time-dependent first outpatient worsening HF, acoramidis continued to reduce risks of all-cause mortality or recurrent cardiovascular hospitalization and first cardiovascular hospitalization versus placebo.

The findings suggest that outpatient worsening HF is associated with adverse clinical outcomes in ATTR-CM. Acoramidis reduced worsening HF events, with benefits emerging early and persisting throughout follow-up.