Transthyretin stabilizer targeting for transthyretin amyloid cardiomyopathy: A systematic review and meta-analysis

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease caused by cardiac amyloid deposition. Transthyretin stabilizers (TTRS) are a potential treatment, but their efficacy and safety remain uncertain. This study aims to evaluate the effects of TTRS on all-cause mortality, functional capacity, quality of life, and adverse events in ATTR-CM patients.

A systematic review and meta-analysis was conducted in February 2025 using Cochrane Central, PubMed, and Embase to identify clinical trials and observational studies comparing TTRS versus no-TTRS therapies. Two reviewers independently assessed study eligibility and extracted data. Outcomes were analyzed using odds ratios (OR) and mean differences (MD) with 95% confidence intervals. Heterogeneity was evaluated using I² statistics, and sensitivity analyses were performed where appropriate. Risk of bias was assessed using ROBINS-I V2 and RoB 2 tools.

Seventeen studies with 5209 participants (2399 TTRS; 2810 controls) were included. TTRS significantly reduced all-cause mortality (OR 0.20; 95% CI 0.11-0.37; p<0.01). In the tafamidis subgroup, the effect remained significant (OR 0.25; 95% CI 0.13-0.48; p<0.01). No mortality benefit was observed in groups with mixed tafamidis doses (OR 0.75; 95% CI 0.41-1.38; p=0.14). TTRS improved quality of life (KCCQ-OS: MD 11.70) and functional capacity (6-minute walk test: SMD 50.68). Fewer adverse events (OR 0.19) and serious events (OR 0.54) were reported, with no difference in severe events.

TTRS, especially tafamidis, reduce mortality and improve outcomes in ATTR-CM.