Real-world effectiveness of targeted therapies in ATTR cardiomyopathy: A meta-analysis integrating population-based data

Abstract

Aims: The aim of this meta-analysis was to evaluate the effects of targeted treatments for transthyretin amyloid cardiomyopathy (ATTR-CM) on clinical outcomes by integrating clinical trial and real-world data. Methods and results: A systematic literature search of PubMed was conducted up to 30 June 2025. A total of 714 relevant records were identified; out of 51 potentially eligible studies, 10 randomized placebo-controlled and non-randomized control comparison studies were selected, with available outcome data on all-cause mortality and cardiovascular hospitalizations. The estimates were extrapolated to real-world outcome data of untreated ATTR-CM patients to estimate absolute risk reduction (ARR) and number needed to treat (NNT). Ten studies comprising 5203 patients were included. ATTR-targeted treatments reduced mortality by 39% [risk ratio (RR) 0.61, 95% confidence interval (CI): 0.52 to 0.70, I2 = 35%, P = 0.13]. A sensitivity subgroup analysis for RCT only confirmed a 28% reduction in all-cause mortality (RR 0.72, 95% CI: 0.60 to 0.86, I2 = 0%, P = 0.56). The random effects model for cardiovascular hospitalizations demonstrated a 31% reduction in the ATTR-targeted treatment group compared with control (RR: 0.69, 95% CI: 0.53 to 0.89, I2 = 68%, P = 0.01). By applying these estimates to published large-scale epidemiological data on the natural disease course from 18238 untreated patients, the estimated NNT of ATTR-CM therapeutics to prevent one death is an NNT of 10 at 2 years and an NNT of 5 at 5 years. Conclusions: Targeted treatments for ATTR-CM significantly reduce mortality and cardiovascular hospitalizations. When extrapolated to population-level data, these treatments show clinical benefits, emphasizing the importance of early diagnosis and therapeutic intervention.