{"id":"0d343dd9b944","type":"article","url":"https://hartvaat.nl/2026/05/12/cadence-sotatercept-verlaagt-pulmonale-vaatweerstand-bij-gecombineerde-pre-postc/","title":"CADENCE: sotatercept verlaagt pulmonale vaatweerstand bij gecombineerde pre/postcapillaire PH bij HFpEF","title_en":"","category":"hartfalen","category_label":"Hartfalen","professions":["cardioloog","internist"],"tags":["heart-failure-2026","summit-trial"],"journal":"Circulation","doi":"10.1161/CIRCULATIONAHA.126.079918","source_url":"https://doi.org/10.1161/CIRCULATIONAHA.126.079918","authors":["Mardi Gomberg-Maitland","Ryan J. Tedford","David Langleben","Stephan Rosenkranz","Barry Miller"],"significance":9,"published":"2026-05-12","source_date":"2026-05-12","image":"","kennis":["https://hartvaat.nl/kennis/diagnostiek/invasieve-hemodynamiek-rechts-hartkatheterisatie/","https://hartvaat.nl/kennis/hartfalen/rechtsventrikelfalen/"],"congress":"heart-failure-2026","summary_en":"CADENCE (n=164, multicentre, randomized, placebo-controlled phase 2) tested sotatercept (activin signalling inhibitor) in patients with combined post- and pre-capillary pulmonary hypertension (CpcPH) in HFpEF. PVR at week 24 dropped by −1.02 Wood units (95% CI −1.81 to −0.23; p=0.004) at the 0.3 mg/kg dose and −0.75 (p=0.024) at 0.7 mg/kg. Mean PAP fell by ~9 mmHg, wedge pressure by 2.5–3 mmHg, 6-min walk improved 20.3 m at the lower dose. Proof of concept for the first therapy in CpcPH-HFpEF, a high-mortality phenotype without approved treatment. Major extension of the sotatercept (WINREVAIR) platform from PAH into HFpEF-PH. (Originally presented at ACC.26 in March; full Circulation publication during HF26.)","created":"2026-07-03T10:32:55Z","updated":"2026-07-03T13:31:50Z","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":"CADENCE — multicentrische, gerandomiseerde, placebogecontroleerde fase 2-trial — testte sotatercept (een activine-signaal-remmer) bij 164 patiënten met gecombineerde post- en precapillaire pulmonale hypertensie (CpcPH) bij HFpEF. Patiënten kregen sotatercept 0,3 of 0,7 mg/kg of placebo elke 3 weken; mediane PVR op baseline 5,2 Wood-eenheden, gemiddelde leeftijd 75 jaar, 70% vrouw. Primair eindpunt — verandering van pulmonale vaatweerstand op week 24 — daalde met sotatercept versus placebo: Hodges-Lehmann-shift −1,02 Wood-eenheden (95% BI −1,81 tot −0,23; p=0,004) bij 0,3 mg/kg en −0,75 (p=0,024) bij 0,7 mg/kg. Mediane pulmonale arteriedruk daalde met ~9 mmHg in beide armen, wedge-druk met 2,5–3 mmHg, 6-minuten-looptest +20,3 m bij de lagere dosis. Meest voorkomende bijwerkingen: hemoglobinestijging en diarree. Conclusie: eerste 'proof of concept' voor sotatercept bij CpcPH-HFpEF — een fenotype zonder bewezen therapie en hoge sterfte. De 0,3 mg/kg dosis biedt het meest aantrekkelijke efficacy-safety profiel voor fase 3. Belangrijke uitbreiding van het sotatercept-platform van PAH naar HFpEF-geassocieerde PH; volgt op WINREVAIR-goedkeuring voor PAH in 2024. (CADENCE werd voor het eerst gepresenteerd op ACC.26 in maart; volledige publicatie in Circulation tijdens HF26.)","abstract_original":"BACKGROUND: Combined post- and pre-capillary pulmonary hypertension in heart failure with preserved ejection fraction (CpcPH-HFpEF) involves remodeling in both the heart and pulmonary vasculature. Despite significant mortality, there are no proven therapies. METHODS: In this multicenter, randomized, placebo-controlled, phase 2 trial, adults received sotatercept (0.3 or 0.7 mg/kg) or placebo every 3 weeks. The primary end point was change in pulmonary vascular resistance at week 24. Hodges-Lehmann shift estimates described placebo-adjusted changes. RESULTS: 164 patients were randomized 54:55:55 to sotatercept 0.3 mg/kg, 0.7 mg/kg, and placebo (mean age 75, 70% women). Baseline median pulmonary vascular resistance was 5.2 (IQR 4.0–6.9) Wood units. The Hodges-Lehmann shift in pulmonary vascular resistance was −1.02 Wood units (95% CI −1.81 to −0.23; P=0.004) for 0.3 mg/kg and −0.75 (95% CI −1.52 to 0.03; P=0.024) for 0.7 mg/kg sotatercept. Mean pulmonary arterial pressure dropped by ~9 mmHg in both sotatercept groups, with reductions in pulmonary arterial wedge pressure of 3 and 2.5 mmHg. 6-minute walk distance improved 20.3 m at 0.3 mg/kg (95% CI 1.5–39.1) and 5.8 m at 0.7 mg/kg. Most common adverse events were increased haemoglobin and diarrhea. CONCLUSIONS: These findings provide proof of concept for improved pulmonary vascular and cardiac hemodynamics following activin signalling inhibition with sotatercept in patients with CpcPH-HFpEF. The 0.3 mg/kg dose had the most attractive efficacy-safety profile for phase 3 development."}