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

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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