{"id":"35d3006b7e26","type":"article","url":"https://hartvaat.nl/2026/06/30/vutrisiran-remt-ttr-en-vermindert-valrisico-bij-attr-cardiomyopathie-meta-analys/","title":"Vutrisiran remt TTR en vermindert valrisico bij ATTR-cardiomyopathie — meta-analyse","title_en":"Clinical outcomes with vutrisiran in transthyretin amyloidosis: a systematic review and meta-analysis of randomized trials.","category":"hartfalen","category_label":"Hartfalen","professions":["cardioloog","internist"],"tags":[],"journal":"Global cardiology science & practice","doi":"10.21542/gcsp.2026.25","source_url":"https://doi.org/10.21542/gcsp.2026.25","authors":["Faizan Ahmed","Faseeh Haider","Ayesha Zulfiqar","Tooba Nihal","Maliha Khalid","Areej Dar","Saman Rauf","Noor Ul Ain Saleem","Hassan Farooq","Haris Bin Tahir","Ramsha Ali","Haider Hussain Shah","Swapnil Patel","Mohammad Hossain","Fawaz Alenezi"],"significance":6,"published":"2026-08-11","source_date":"2026-06-30","image":"","kennis":["https://hartvaat.nl/kennis/hartfalen/palliatief-hartfalen/","https://hartvaat.nl/kennis/farmacologie/antiaritmica-farmacologie/"],"congress":"","summary_en":"A systematic review and meta-analysis of three RCTs (HELIOS-A, HELIOS-B, and a phase-1 trial, n=976) demonstrates that vutrisiran, an RNA interference therapy, reduces transthyretin (TTR) levels by up to 97% with durable suppression. While the analysis suggests trends toward improved quality of life, functional capacity, and mortality (RR 0.51; p=0.29), these did not reach statistical significance. Vutrisiran significantly reduced fall risk (RR 0.62; p=0.001) without increasing overall adverse events, indicating a favourable safety profile. These findings confirm robust biomarker suppression and safety, but larger long-term trials are required to definitively establish clinical and survival benefits in transthyretin amyloidosis.","created":"2026-08-05T00:46:58Z","updated":"2026-08-10T10:36:11Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Een systematische review en meta-analyse van drie RCTs (HELIOS-A, HELIOS-B en een fase-1studie, n=976) toont aan dat vutrisiran, een RNAi-therapie, de transthyretine (TTR)-concentratie met tot wel 97% verlaagt en dit effect duurzaam handhaaft. Hoewel de meta-analyse een trend naar minder sterfte (RR 0,51; p=0,29) en verbeterde functionele capaciteit en kwaliteit van leven suggereerde, bereikten deze uitkomsten geen statistische significantie. Wel werd het valrisico significant gereduceerd (RR 0,62; p=0,001) zonder toename van bijwerkingen. Voor de klinische praktijk bevestigt dit een gunstig veiligheidsprofiel en sterke biomarker-remming, maar grotere, langdurige trials zijn nodig om overlevings- en functionele voordelen definitief aan te tonen.","abstract_original":"Background: Transthyretin amyloidosis (ATTR) is a progressive disease that causes a restrictive cardiomyopathy. Vutrisiran, a subcutaneous RNA interference (RNAi) therapy, is an approved treatment. This systematic review and meta-analysis evaluates its efficacy and safety with respect to transthyretin (TTR) reduction, functional capacity, quality of life, mortality, and adverse events. Methods: We identified 1,032 records, of which three randomized controlled trials-HELIOS-A, HELIOS-B, and a Phase 1 study-comprising 976 participants (508 vutrisiran; 468 comparator) met the inclusion criteria. Comparator participants received placebo, patisiran (an active reference comparator in HELIOS-A), or external placebo from the APOLLO trial. Outcomes assessed were TTR reduction, functional capacity, quality of life, mortality, and adverse events, pooled using random-effects models reporting mean differences and risk ratios. Results: Vutrisiran achieved a rapid, durable TTR reduction of up to 97% in healthy volunteers at the highest dose, and a sustained steady-state reduction in the HELIOS-A and HELIOS-B trials. QoL outcomes showed a protective effect of vutrisiran, with slowed deterioration in the intervention group. Functional outcomes (10-MWT, 6-MWT) suggested slower decline in mobility and functional capacity. Mortality showed a non-significant reduction (RR 0.51; p = 0.29; I2 = 62%), with most deaths considered unrelated to treatment. The safety analysis showed fewer falls (RR 0.62; p = 0.001; I2 = 0%) but no significant difference in overall adverse events (AEs) (RR 1.01; p = 0.76) or serious AEs (RR 0.82; p = 0.23). A sensitivity analysis supported the adverse-event findings. Conclusions: Vutrisiran consistently suppressed TTR and showed signals of benefit in quality of life, function, and mortality, though most of these outcomes did not reach statistical significance. It reduced fall risk without increasing adverse events, indicating a favourable safety profile. Larger, long-term RCTs are needed to confirm survival and functional benefits."}