Summary
A medRxiv preprint pooling five phase III trials reports lower all-cause mortality and better functional and health-status outcomes with disease-modifying treatments for transthyretin amyloid cardiomyopathy. Exploratory subgroup results found smaller effects on several non-mortality measures among patients taking a background stabilizer.
A systematic review and meta-analysis posted as a medRxiv preprint reports that disease-modifying treatments were associated with lower pooled all-cause mortality and better functional and health-status outcomes in people with transthyretin amyloid cardiomyopathy (ATTR-CM). The analysis combined results from five phase III, placebo-controlled randomised trials involving 3,497 participants; it has not yet been peer reviewed.
ATTR-CM is a heart condition in which transthyretin protein forms deposits in the heart. The preprint examines treatments intended to alter the disease process, rather than looking at a single drug or trial. Its authors searched PubMed, Embase and the Cochrane Library for eligible trials published through September 2026, then pooled outcomes using a random-effects model.
Pooled results across five trials
The analysis reported a risk ratio for all-cause mortality of 0.76 (95% confidence interval 0.66–0.87; I²=0%). This corresponds to a lower relative risk in the treatment groups than in the placebo groups; the abstract does not provide absolute event rates. The authors also found results favouring treatment for six-minute walk distance (standardised mean difference [SMD] 0.43; 95% CI 0.20–0.67) and the Kansas City Cardiomyopathy Questionnaire Overall Summary score (SMD 0.37; 95% CI 0.19–0.55). The latter is a measure of heart-failure-related health status. NT-proBNP, a blood marker used in assessing cardiac strain, was lower with treatment (SMD −0.53; 95% CI −0.89 to −0.18).
These are pooled standardised effects, not changes expressed in metres or questionnaire points. The trials included different disease-modifying treatments, and the preprint notes that differences in trial design and use of background stabiliser therapy complicate comparisons.
Results by background stabiliser use
The researchers compared treatment effects for patients receiving disease-modifying therapy alone with effects for those also taking a stabiliser at baseline. For mortality, the pooled risk ratios were 0.77 and 0.71, respectively; the difference between these subgroups was not statistically significant (P for interaction = 0.59).
For other outcomes, the estimated treatment effects were smaller in the stabiliser group: SMDs were 0.49 versus 0.14 for six-minute walk distance, 0.44 versus 0.07 for KCCQ-OS, and −0.65 versus −0.13 for NT-proBNP. The reported interaction P values were 0.012, less than 0.001 and 0.029, respectively. The authors characterise these subgroup analyses as exploratory. They suggest a difference in the size of effects on these measures across the groups, not that stabiliser use has been shown to cause the difference.
Because this is a preprint synthesis of trial results, the findings are best read as pooled evidence across the included studies. The mortality subgroup comparison did not identify a statistically significant difference by stabiliser use, while the estimates for functional capacity, health status and NT-proBNP varied between the groups.