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This meta-analysis of five phase III randomized controlled trials involving 3,497 patients with transthyretin amyloid cardiomyopathy (ATTR-CM) found that disease-modifying therapies reduced all-cause mortality by 24% and improved functional capacity, quality of life, and cardiac biomarkers. The mortality benefit was similar regardless of whether patients were also taking background stabilizer medications, though improvements in walking distance, symptom scores, and NT-proBNP levels were smaller when disease-modifying therapy was added to existing stabilizer treatment. These findings suggest disease-modifying treatments provide meaningful clinical benefits across different treatment scenarios in ATTR-CM.
Why it matters
This analysis helps clarify the effectiveness of newer disease-modifying treatments for a progressive and fatal heart condition, providing evidence that these therapies extend survival and improve patient outcomes. The findings also inform clinical decision-making about whether to use these treatments alone or in combination with stabilizer medications.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Background Several disease-modifying agents for transthyretin amyloid cardiomyopathy (ATTR-CM) have been investigated, but differences in trial design and background stabilizer use complicate interpretation of their efficacy. This meta-analysis assessed their efficacy overall and by background stabilizer use. Methods PubMed, Embase, and the Cochrane Library were searched through September 2026 for phase III randomized, placebo-controlled trials of disease-modifying therapy in ATTR-CM. Primary endpoints were all-cause mortality, 6-minute walk distance (6MWD), Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score, and N-terminal pro-B-type natriuretic peptide (NT-proBNP), pooled with a random-effects model. Treatment effects were compared between the monotherapy and baseline stabilizer strata using a mixed-effects model. Results Five trials (ATTR-ACT, APOLLO-B, ATTRibute-CM, HELIOS-B, CARDIO-TTRansform; N=3497) were included. Disease-modifying therapy reduced all-cause mortality (risk ratio, 0.76; 95% confidence interval [CI], 0.66-0.87; I2=0%) and improved 6MWD (pooled standardized mean difference [SMD], 0.43; 95% CI, 0.20-0.67), KCCQ-OS score (SMD, 0.37; 95% CI, 0.19-0.55), and NT-proBNP (SMD, -0.53; 95% CI, -0.89 to -0.18). The mortality benefit was similar whether therapy was given alone or added to a background stabilizer (pooled risk ratio, 0.77 vs. 0.71; P for interaction = 0.59), but treatment effects on 6MWD (pooled SMD, 0.49 vs. 0.14), KCCQ-OS score (0.44 vs. 0.07), and NT-proBNP (-0.65 vs. -0.13) were smaller among patients receiving a background stabilizer (P for interaction = 0.012, <0.001, and 0.029, respectively). Conclusion Disease-modifying treatments reduced all-cause mortality and favored functional capacity, health status, and NT-proBNP outcomes in patients with ATTR-CM. Exploratory subgroup analyses showed smaller treatment effects on 6MWD, KCCQ-OS score, and NT-proBNP among patients receiving a background stabilizer, with no statistically significant difference in the mortality effect according to baseline stabilizer use.