Targeted Therapies Reduce Mortality and Hospitalizations in ATTR-CM

Targeted therapies for transthyretin amyloid cardiomyopathy (ATTR-CM) were associated with significant reductions in all-cause mortality and cardiovascular hospitalizations compared with untreated patients, a study finds.

This real-world meta-analysis is published in ESC Heart Failure.

Meaningful reductions in all-cause mortality and cardiovascular hospitalizations modeled benefits compared with untreated populations. | Image credit: appledesign - stock.adobe.com

“Our analysis provides added evidence compared with published studies by evaluating the effects of four targeted therapies (tafamidis, acoramidis, patisiran, and vutrisiran), integrating evidence from both RCTs [randomized controlled trials] and observational cohorts, and translating pooled RRs into ARRs and NNT based on large-scale natural history data (>18000 untreated patients) to project the absolute survival benefit at a population level,” wrote the researchers.

Cardiomyopathy refers to diseases of the heart muscle that make it harder for the heart to pump blood to the rest of the body.2 It can be acquired or inherited and often leads to symptoms such as shortness of breath, fatigue, swelling in the legs and feet, and irregular heartbeats. Over time, cardiomyopathy can lead to heart failure, heart valve problems, or life-threatening arrhythmias, underscoring the importance of early diagnosis and management.

The researchers searched PubMed through June 30, 2025, to identify studies of targeted ATTR‑CM treatments with available outcomes on all‑cause mortality and cardiovascular hospitalizations.1 From 714 relevant records, 51 potentially eligible studies were screened, and 10 randomized placebo‑controlled and non‑randomized comparison studies were selected for inclusion, comprising a pooled sample of 5203 patients. Estimates from these studies were extrapolated to real-world data from an untreated cohort of 18,238 patients to calculate absolute risk reduction (ARR) and number needed to treat (NNT). The analyses applied random‑effects models for pooled risk ratios (RRs) for mortality and cardiovascular hospitalization outcomes.

Across the 10 studies included in the analysis, targeted treatments were associated with a 39% reduction in all‑cause mortality compared with control (RR, 0.61; 95% CI, 0.52-0.70; I² = 35%; P = 0.13). 1 A subgroup sensitivity analysis restricted to RCTs confirmed a 28% mortality reduction (RR, 0.72; 95% CI, 0.60-0.86; I²=0%; P = 0.56). Cardiovascular hospitalizations were reduced by 31% in patients receiving targeted therapy compared with control (RR, 0.69; 95% CI, 0.53-0.89; I² = 68%; P = 0.01).

When these pooled relative estimates were applied to population-level data from patients with untreated ATTR‑CM, the analysis projected that targeted therapies could prevent 1 death for every 10 patients treated at 2 years (NNT = 10) and every 5 patients treated at 5 years (NNT = 5). These extrapolated benefits reflect combined evidence from stabilizers (such as tafamidis and acoramidis) and silencers (such as patisiran and vutrisiran) used in real‑world and trial settings.

However, the researchers noted some limitations. The meta-analysis combined RCT and observational data, which may introduce bias due to differences in patient selection and disease severity. Variability in ATTR-CM genotype, stage, and therapy timing could affect outcomes. Follow-up durations were relatively short, and projections to real-world populations relied on estimated control event rates that may not fully reflect untreated outcomes.

Despite these limitations, this meta-analysis integrating clinical trial and real-world data provides evidence that targeted therapies for ATTR-CM significantly reduce all-cause mortality and cardiovascular hospitalizations relative to controls.

“Our estimates suggest that ATTR-targeted treatments reduce all-cause mortality by 39% and cardiovascular hospitalizations by 31% in patients with ATTR-CM, with good efficacy in projected real-world data,” wrote the researchers. “Early diagnosis and initiation of treatment are critical to maximize the clinical benefits and prolong patient survival.”

References

1. Antonopoulos AS, Tsampras T, D Terentes-Printzios, et al. Real-world effectiveness of targeted therapies in ATTR cardiomyopathy: A meta-analysis integrating population-based data. ESC Heart Failure. https://onlinelibrary.wiley.com/doi/10.1002/ehf2.70011

2. Cardiomyopathy. Mayo Clinic. February 21, 2024. Accessed February 11, 2026. https://www.mayoclinic.org/diseases-conditions/cardiomyopathy/symptoms-causes/syc-20370709