Heart failure & cardiomyopathiesMeta-analysis
Gene Silencer Therapy in Transthyretin Amyloid Cardiomyopathy
- Systematic review and meta-analysis of randomised trials
- fixed-effects
- placebo-controlled phase 3 trials
Authors' conclusion
The findings from this meta-analysis support TTR gene silencing for ATTR-CM.
Study context
- Population
- Patients with transthyretin amyloid cardiomyopathy (ATTR-CM)
- Participants
- 2,086 patients · 2 RCTs
- Comparison
- TTR gene-silencing therapy vs placebo
- Outcome
- Composite of:
- All-cause mortality
- Recurrent CV events
Pooled result
As reported in the abstract
Relative risk
0.80
95% CI 0.69–0.94
P = 0.006
Gene-silencing therapy vs Placebo
RR 0.80 (95% CI 0.69–0.94); P = 0.006
Further pooled results
| Outcome | Estimate | |
|---|---|---|
| All-cause death | HR 0.74 (95% CI 0.61–0.91) | |
| Time to first all-cause death or CV events | HR 0.77 (95% CI 0.67–0.89) | |
| Primary end point, by baseline stabilizer use (subgroup) — Gene-silencing therapy vs Placebo · no background stabilizer | RR 0.69 (95% CI 0.57–0.85) | |
| Primary end point, by baseline stabilizer use (subgroup) — Gene-silencing therapy vs Placebo · concomitant stabilizer at baseline | RR 0.97 (95% CI 0.77–1.23) | |
| 0.512Ratio (log scale) |
| Outcome | Estimate |
|---|---|
| 6-minute walk distance · no evidence of between-trial heterogeneity | placebo-corrected difference +22.2 m (95% CI 14.3–30.0) |
| KCCQ-Overall Summary Score · no evidence of between-trial heterogeneity | difference +4.5 (95% CI 2.7–6.2) |
- Primary end point, by baseline stabilizer use (subgroup): P for heterogeneity = .03
Primary end point, by baseline stabilizer use (subgroup)
- Similar heterogeneity for functional capacity and health status
Original publication
Gene Silencer Therapy in Transthyretin Amyloid Cardiomyopathy. JAMA. Published 30 August 2026. doi:10.1001/jama.2026.17246
Summarised from the published abstract; every number is checked against it