Journal of cardiac failure · 2025
Amyloid-Specific Medication in Transthyretin Amyloid Cardiomyopathy: A Systematic Review and Meta-Analysis of Cardiovascular Outcome trials.
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Autherith Maximilian, Hauptmann Laurenz, Koschatko Sophia, Jantsch Charlotte, Kronberger Christina, Poledniczek Michael, Halavina Kseniya, Demirel Caglayan, Ristl Robin, Duca Franz, Kammerlander Andreas, Hanna Mazen, Fontana Marianna, Maurer Mathew, Bartko Philipp E, Nitsche Christian
Аннотация
BACKGROUND: The introduction of disease-specific medication has revolutionized the management of transthyretin-associated cardiomyopathy (ATTR-CM). However, dedicated trials included different patient populations, primary endpoints, and follow-up periods, rendering study comparison challenging. This systematic review and meta-analysis aimed to harmonize data from all phase 3 placebo-controlled drug trials in ATTR-CM to elucidate the magnitude and timing of treatment efficacy of ATTR-specific medication.
METHODS: We searched PubMed and Embase for trials published up to February 23, 2025 (PROSPERO: CRD42025645376). Efficacy outcomes included all-cause death, cardiovascular (CV) events, change in 6-minute walk distance, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and Kansas City Cardiomyopathy Questionnaire Overall Score. Outcome metrics were pooled across trials using inverse-variance weighting and a random-effects model.
RESULTS: We included data from 4 identified trials (ATTR-ACT, ATTRibute, APOLLO-B, and HELIOS-B) and 2086 patients. Baseline risk profiles differed substantially, highlighted by a decrease in NT-proBNP and estimated glomerular filtration rate levels from earlier to later trials, likely resulting in different death rates of the respective placebo groups. At 12 months, ATTR-specific medication showed a trend toward less decline in 6-minute walk distance (least squares mean difference: 12.9 meters; 95% confidence interval [CI] -4.1 to 29.8) and was associated with a significantly blunted decline in Kansas City Cardiomyopathy Questionnaire Overall Score (least squares mean difference: 4.7 points; 95% CI 2.3-7.0) and NT-proBNP (geometric mean fold ratio 0.80; 95% CI 0.74-0.85) compared with placebo. These effects are consolidated with continued treatment. At 12-months, ATTR-specific medication did not improve all-cause mortality (OR 1.00; 95% CI 0.69-1.44) compared with placebo. Conversely, over the maximum follow-up period and at 30 months, respectively, ATTR-specific medication reduced the risk of all-cause mortality by 28% (HR 0.72; 95% CI 0.59-0.87) and for CV events by 42% (OR 0.58; 95%CI 0.47-0.73).
CONCLUSIONS: ATTR-specific medication exhibits early salutary effects on blood biomarkers, functional capacity and quality of life. These effects translate into reductions in CV events and all-cause mortality after continued treatment.
METHODS: We searched PubMed and Embase for trials published up to February 23, 2025 (PROSPERO: CRD42025645376). Efficacy outcomes included all-cause death, cardiovascular (CV) events, change in 6-minute walk distance, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and Kansas City Cardiomyopathy Questionnaire Overall Score. Outcome metrics were pooled across trials using inverse-variance weighting and a random-effects model.
RESULTS: We included data from 4 identified trials (ATTR-ACT, ATTRibute, APOLLO-B, and HELIOS-B) and 2086 patients. Baseline risk profiles differed substantially, highlighted by a decrease in NT-proBNP and estimated glomerular filtration rate levels from earlier to later trials, likely resulting in different death rates of the respective placebo groups. At 12 months, ATTR-specific medication showed a trend toward less decline in 6-minute walk distance (least squares mean difference: 12.9 meters; 95% confidence interval [CI] -4.1 to 29.8) and was associated with a significantly blunted decline in Kansas City Cardiomyopathy Questionnaire Overall Score (least squares mean difference: 4.7 points; 95% CI 2.3-7.0) and NT-proBNP (geometric mean fold ratio 0.80; 95% CI 0.74-0.85) compared with placebo. These effects are consolidated with continued treatment. At 12-months, ATTR-specific medication did not improve all-cause mortality (OR 1.00; 95% CI 0.69-1.44) compared with placebo. Conversely, over the maximum follow-up period and at 30 months, respectively, ATTR-specific medication reduced the risk of all-cause mortality by 28% (HR 0.72; 95% CI 0.59-0.87) and for CV events by 42% (OR 0.58; 95%CI 0.47-0.73).
CONCLUSIONS: ATTR-specific medication exhibits early salutary effects on blood biomarkers, functional capacity and quality of life. These effects translate into reductions in CV events and all-cause mortality after continued treatment.