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, I 2 = 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, I 2 = 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, I 2 = 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.
Charalambos Vlachopoulos (Fri,) studied this question.