{"id":"46057","type":"article","url":"https://hartvaat.nl/2026/04/21/jacc-beschouwing-placebo-in-trials-met-incretine-therapie-bij-hartfalen-wetensch/","title":"JACC-beschouwing: placebo in trials met incretine-therapie bij hartfalen — wetenschap versus ethiek","title_en":"Balancing Clinical and Ethical Considerations Related to Placebo Use in Trials of Incretin-Based Therapies in Heart Failure.","category":"hartfalen","category_label":"Hartfalen","professions":["cardioloog"],"tags":[],"journal":"Journal of the American College of Cardiology","doi":"10.1016/j.jacc.2026.02.5086","source_url":"https://doi.org/10.1016/j.jacc.2026.02.5086","authors":["Francesco Fioretti","Mark C Petrie","Neal W Dickert","Javed Butler"],"significance":5,"published":"2026-07-18","source_date":"2026-04-21","image":"","kennis":["https://hartvaat.nl/kennis/hartfalen/hfpef-hartfalen-met-behouden-ejectie/","https://hartvaat.nl/kennis/farmacologie/glp1-agonisten-cardiologie/"],"congress":"","summary_en":"GLP-1 receptor agonists and dual GIP/GLP-1 agonists improve symptoms and function in heart failure with preserved ejection fraction (HFpEF) and obesity, but the trials were small with few hard events. At the same time, these drugs have proven cardiovascular and renal benefits in obesity, diabetes and kidney disease, raising questions about placebo use in future heart-failure trials. In this JACC viewpoint, the authors weigh the scientific, practical and ethical considerations: placebo ensures methodologic rigour but may be ethically problematic given the cardiometabolic benefit, whereas abandoning placebo risks incomplete safety and efficacy data. They introduce a structured framework for when placebo remains appropriate, when active comparison is needed, and how trial design can address the ethical and operational challenges — aiming for definitive evidence to inform guidelines and reimbursement.","created":"2026-07-03T20:27:11Z","updated":"2026-07-04T19:26:57Z","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":"GLP-1-receptoragonisten en duale GIP/GLP-1-agonisten verbeteren de klachten en het functioneren bij hartfalen met behouden ejectiefractie (HFpEF) en obesitas, maar de trials waren klein met weinig harde events. Tegelijk hebben deze middelen bewezen voordeel op cardiovasculaire en renale uitkomsten bij obesitas, diabetes en nierziekte, wat vragen oproept over het gebruik van placebo in toekomstige hartfalentrials. In deze JACC-beschouwing wegen de auteurs de wetenschappelijke, praktische en ethische overwegingen: placebo waarborgt methodologische strengheid maar kan ethisch problematisch zijn gezien de cardiometabole winst, terwijl het loslaten van placebo het risico geeft op onvolledige veiligheids- en effectiviteitsdata. Zij introduceren een gestructureerd kader voor wanneer placebo gepast blijft, wanneer een actieve vergelijking nodig is, en hoe de trialopzet de ethische en operationele uitdagingen kan adresseren — met als doel definitief bewijs voor richtlijnen en vergoeding.","abstract_original":"Recent trials have shown that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dual gastric inhibitory polypeptide/GLP-1 RAs improve symptoms and functional capacity in patients with heart failure (HF) with preserved ejection fraction and obesity, with or without type 2 diabetes. These studies enrolled modest sample sizes and had few worsening HF events or cardiovascular (CV) deaths, limiting definitive conclusions regarding those endpoints. At the same time, the benefits of these drugs on major adverse CV and kidney outcomes in patients with obesity, diabetes, and chronic kidney disease raise questions about placebo-controlled designs in future HF trials. This article explores scientific, practical, and ethical considerations surrounding the design of future incretin-based therapy trials in HF. We highlight the current gaps in evidence and emphasize the need for event-driven outcome trials in HF. The use of placebo ensures methodologic rigor but may raise ethical concerns in the context of cardiometabolic benefit with GLP-1 RAs. Abandoning placebo, however, risks incomplete safety and efficacy data and premature therapeutic extrapolation. Such studies are essential to define the efficacy, durability, and safety of incretin-based therapy across the HF spectrum and to clarify whether improvements in patient-reported outcomes are bolstered by other benefits. To support balanced decision making, we introduce a structured framework outlining when placebo remains appropriate, when active comparison may be required, and how trial design features can address the ethical and operational challenges unique to incretin-based HF research. Ethically robust, clinically focused, and methodologically rigorous trials remain the only means to inform guideline recommendations and insurance coverage. The HF population is too large, too vulnerable, and too costly to remain without definitive evidence guiding the use of these therapies."}