Heart failure & cardiomyopathiesMeta-analysis
Timing of Mortality Benefit in Outcomes Trials in Transthyretin Amyloidosis
- Pooled reconstructed-data analysis of 3 randomised trials
- time-to-event data extracted from published Kaplan-Meier curves
- flexible parametric survival models
Authors' conclusion
TTR silencers and stabilizers in ATTR-CM confer a delayed but consistent mortality benefit with no significant differences observed between the 3 major trials.
Study context
- Population
- Patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) in ATTR-ACT (tafamidis), ATTRIBUTE-CM (acoramidis) and HELIOS-B (vutrisiran)3 RCTs
- Comparison
- TTR stabilizers and silencers vs placebo
- Outcome
- Time course of mortality benefit (time-varying instantaneous HRs)
Pooled result
As reported in the abstract
Time-varying mortality treatment effect
Consistent time-varying treatment effects across trials
P = 0.96
Pooled model: delayed but progressively strengthening benefit, treatment effect
P < 0.001
Pooled model: time interaction
P < 0.001
Original publication
Timing of Mortality Benefit in Outcomes Trials in Transthyretin Amyloidosis. J Am Coll Cardiol. Published 25 September 2025. doi:10.1016/j.jacc.2025.09.1512
Summarised from the published abstract; every number is checked against it