{"doi":"10.1016/j.cardfail.2025.08.002","title":"Amyloid-Specific Medication in Transthyretin Amyloid Cardiomyopathy: A Systematic Review and Meta-Analysis of Cardiovascular Outcome trials","abstract":"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.","journal":"Journal of Cardiac Failure","year":2025,"id":573763,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1480917,"name":"Laurenz Hauptmann","orcid":"0000-0003-2674-3796","position":1,"is_corresponding":false},{"id":1480918,"name":"Sophia Koschatko","orcid":"0000-0003-0918-8217","position":2,"is_corresponding":false},{"id":1480919,"name":"Charlotte Jantsch","orcid":"0009-0004-0780-0526","position":3,"is_corresponding":false},{"id":1480920,"name":"Christina Kronberger","orcid":"0000-0002-3866-3710","position":4,"is_corresponding":false},{"id":1480921,"name":"Michael Poledniczek","orcid":"0000-0002-6091-9823","position":5,"is_corresponding":false},{"id":1481291,"name":"Kseniya Halavina","orcid":null,"position":6,"is_corresponding":false},{"id":1480922,"name":"Caglayan Demirel","orcid":"0009-0001-1966-0637","position":7,"is_corresponding":false},{"id":1480923,"name":"Robin Ristl","orcid":"0000-0002-4163-9236","position":8,"is_corresponding":false},{"id":1480924,"name":"Franz Duca","orcid":"0000-0002-7519-5274","position":9,"is_corresponding":false},{"id":690882,"name":"Andreas A. Kammerlander","orcid":"0000-0002-7632-9879","position":10,"is_corresponding":false},{"id":640260,"name":"Mazen Hanna","orcid":"0000-0002-7251-3003","position":11,"is_corresponding":false},{"id":70689,"name":"Marianna Fontana","orcid":null,"position":12,"is_corresponding":false},{"id":239734,"name":"Matthew J. Maurer","orcid":"0000-0002-1867-0526","position":13,"is_corresponding":false},{"id":299708,"name":"Philipp E. Bartko","orcid":"0000-0001-9061-4839","position":14,"is_corresponding":false},{"id":1480925,"name":"Christian Nitsche","orcid":"0000-0002-0141-7639","position":15,"is_corresponding":false},{"id":1480916,"name":"Maximilian Autherith","orcid":"0000-0003-1765-007X","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:57:36.753600Z","pmid":"40889572","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}