ATTRibute-CM
Trial question
What is the effect of acoramidis in patients with transthyretin amyloid cardiomyopathy?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
10.0% female
90.0% male
N = 632
632 patients (62 female, 570 male).
Inclusion criteria: patients with transthyretin amyloid cardiomyopathy.
Key exclusion criteria: acute coronary syndrome, coronary revascularization, stroke, or TIA in the past 90 days; likely heart transplantation within a year after screening; AL amyloidosis; eGFR < 15 mL/min/1.73 m².
Interventions
N=421 acoramidis (at a dose of 800 mg BID for 30 months).
N=211 placebo (matching placebo BID for 30 months).
Primary outcome
Favorable pairwise comparisons in a hierarchical outcome of death from any cause, cardiovascular-related hospitalization, change from baseline in N-terminal pro-brain natriuretic peptide level, and change from baseline in the 6-minute walk distance at month 30
63.7%
35.9%
63.7 %
47.8 %
31.9 %
15.9 %
0.0 %
Acoramidis
Placebo
Significant
increase ▲
NNT = 3
Significant increase in favorable pairwise comparisons in a hierarchical outcome of death from any cause, cardiovascular-related hospitalization, change from baseline in the NT-proBNP level, and change from baseline in the 6-minute walk distance at month 30 (63.7% vs. 35.9%; WR 1.8, 95% CI 1.4 to 2.2).
Secondary outcomes
Significantly greater improvement in least-square mean 6-minute walk distance at month 30 (65.1 m vs. 104.5 m; MD 39.6, 95% CI 21.1 to 58.2).
Significantly greater improvement in least-squares mean QoL, assessed by Kansas City Cardiomyopathy Questionnaire-Overall Summary at month 30 (11.5 points vs. 21.5 points; MD 9.94, 95% CI 5.97 to 13.91).
Significantly greater reduction in least-squares mean serum transthyretin level (5.75 mg/dL vs. -1.35 mg/dL; MD 7.01, 95% CI 5.79 to 8.4).
Safety outcomes
No significant difference in adverse events.
Conclusion
In patients with transthyretin amyloid cardiomyopathy, acoramidis was superior to placebo with respect to favorable pairwise comparisons in a hierarchical outcome of death from any cause, cardiovascular-related hospitalization, change from baseline in the NT-proBNP level, and change from baseline in the 6-minute walk distance at month 30.
Reference
Julian D Gillmore, Daniel P Judge, Francesco Cappelli et al. Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2024 Jan 11;390(2):132-142.
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