Cardiovascular Hospitalization Associated With Increased Mortality Risk in ATTR-CM

A new analysis of the phase 3 ATTRibute-CM study has highlighted an association between cardiovascular-related hospitalization (CVH) and increased risk of all-cause mortality (ACM) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).1

These data were presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026 in Phoenix, Arizona, by Quan Bui, MD, assistant professor of medicine in advanced heart failure and transplant cardiology at University of California San Diego Health.1

“CVH, a known predictor of mortality in patients with general heart failure, is not well characterized in ATTR-CM,” Bui and colleagues wrote. “The relationship between CVH burden and survival has not been fully evaluated.”1

ATTRibute-CM was a phase 3, double-blind trial evaluating the efficacy of acoramidis, a high-affinity transthyretin (TTR) stabilizer, in patients with ATTR-CM. Patients were eligible for inclusion if they were between the ages of 18 and 90 years, had an established diagnosis of ATTR-CM, and had clinical heart failure with ≥1 previous hospitalization, among other criteria. Patients with acute coronary syndrome, coronary revascularization, or stroke within 90 days before screening were excluded, among other criteria.2

Eligible patients were randomly assigned in a 2:1 ratio to either acoramidis hydrochloride 800 mg or matching placebo twice daily for 30 months. The primary outcome was a 4-step hierarchical analysis including death from any cause, cumulative frequency of CVH, change from baseline in NT-proBNP levels, and change from baseline in 6-minute walk distance. Key secondary outcomes included change from baseline in 6-minute walk distance and Kansas City Cardiomyopathy Questionnaire—Overall Summary (KCCQ-OS) score, among others.2

A total of 632 patients were ultimately enrolled in the trial – of these, 421 received acoramidis and 211 received placebo. 21 patients with stage 4 kidney disease (12 from the treatment arm and 9 from placebo) were excluded from the primary analysis. Of the remaining 611, investigators saw that the primary analysis favored acoramidis (P <.001), with a corresponding win ratio of 1.8 (95% CI, 1.4-2.2). 63.7% of pairwise comparisons favored acoramidis, while 35.9% favored placebo.2

In the present analysis, Bui and colleagues created a modified intention-to-treat population including all patients with baseline estimated glomerular filtration rates ≥30 mL/min/1.73m2. In particular, they evaluated patients who experienced 0, 1, and ≥2 CVH events during the study, which were defined as nonelective admissions to acute care settings for cardiovascular-related morbidity or an urgent heart failure visit.1

Of the 611 total patients, 416 exhibited no CVH events, 117 had 1 CVH event, and 78 had ≥2 CVH events. Patients with 0, 1, and ≥2 CVH events differed by baseline NT-proBNP (median, 2046, 2473, and 2881 pg/mL, respectively) and variant ATTR-CM (7.5, 12, and 17.9%, respectively).1

Bui and colleagues noted that survival decreased progressively with increasing CVH burden during the study’s 30-month follow-up period, and ACM risk substantially rose with an increasing number of CVH events. Survival probability was ultimately 86.7% in patients with 0 CVH events (95% CI, 82.9-89.7%), 68.4% in patients with 1 CVH event (95% CI, 59.1-76%), and 47.7% in patients with ≥2 CVH events (95% CI, 35.9-58.6%). The team concluded that this demonstrated an incremental increase in mortality risk across levels of CVH burden.1

“In ATTRibute-CM, a higher burden of CVH events was associated with a significantly higher subsequent risk of ACM over 30 months,” Bui and colleagues wrote. “The association between CVH reduction with effective therapies and improved survival warrants further study.”1

References

1. Bui Q, Soman P, Emdin M, et al. Association Between the Burden of Cardiovascular-related Hospitalizations and All-Cause Mortality in Transthyretin Amyloid Cardiomyopathy: Insights from ATTRibute-CM. Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026, Phoenix, AZ. October 9-12, 2026.

2. Gillmore JD, Judge DP, Cappelli F, et al. Efficacy and safety of ACORAMIDIS in transthyretin amyloid cardiomyopathy. NEJM. 2024;390(2):132-142. doi:10.1056/nejmoa2305434