{"id":"6fbefb906b1c","type":"article","url":"https://hartvaat.nl/2019/02/26/sacubitril-valsartan-en-biomarkers-van-extracellulaire-matrixregulatie-bij-hfref/","title":"Sacubitril/valsartan en biomarkers van extracellulaire matrixregulatie bij HFrEF","title_en":"Effects of Sacubitril/Valsartan on Biomarkers of Extracellular Matrix Regulation in Patients With HFrEF.","category":"hartfalen","category_label":"Hartfalen","professions":["cardioloog"],"tags":["bloeddrukbehandeling","sacubitril-valsartan"],"journal":"Journal of the American College of Cardiology","doi":"10.1016/j.jacc.2018.11.042","source_url":"https://doi.org/10.1016/j.jacc.2018.11.042","authors":["Michael R Zile","Eileen O'Meara","Brian Claggett","Margaret F Prescott","Scott D Solomon","Karl Swedberg","Milton Packer","John J V McMurray","Victor Shi","Martin Lefkowitz","Jean Rouleau"],"significance":5,"published":"2019-02-26","source_date":"2019-02-26","image":"","kennis":["https://hartvaat.nl/kennis/hartfalen/ivabradine-bij-hartfalen/","https://hartvaat.nl/kennis/farmacologie/arni-farmacologie/"],"congress":"","summary_en":"This study showed that sacubitril-valsartan reduces biomarkers of extracellular matrix regulation (collagen turnover, fibrosis) in HFrEF, providing mechanistic evidence for anti-fibrotic effects of combined neprilysin-RAAS inhibition.","created":"2026-07-03T10:27:47Z","updated":"2026-07-03T13:27:00Z","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":"Studie naar het effect van sacubitril/valsartan op biomarkers van extracellulaire matrixregulatie (fibrose) bij HFrEF. Mechanistisch inzicht.","abstract_original":"BACKGROUND: Myocardial fibrosis is an important pathophysiological mechanism underlying the development of heart failure (HF). Given the biochemical targets of sacubitril/valsartan, we hypothesized that circulating biomarkers reflecting the mechanisms that determine extracellular matrix (ECM) homeostasis, including collagen synthesis, processing, and degradation, are altered by sacubitril/valsartan in comparison to enalapril. OBJECTIVES: The purpose of this study was to examine the effects of sacubitril/valsartan on biomarkers of ECM homeostasis and the association between the rate of primary composite outcome (cardiovascular death or HF hospitalization) and these biomarkers. METHODS: Biomarkers at baseline (n = 2,067) and both baseline and 8 months after randomization (n = 1,776) included aldosterone, soluble ST2 (sST2), tissue inhibitor of matrix metalloproteinase (TIMP)-1, matrix metalloproteinase (MMP)-2, MMP-9, Galectin-3 (Gal-3), N-terminal propeptide of collagen I (PINP), and N-terminal propeptide of collagen III (PIIINP). The effects of sacubitril/valsartan on biomarkers were compared with enalapril. Baseline biomarker values and changes from baseline to 8 months were related to primary outcome. RESULTS: At baseline, the profibrotic biomarkers aldosterone, sST2, TIMP-1, Gal-3, PINP, and PIIINP were higher, and biomarkers associated with collagen degradation, MMP-2 and -9, were lower than published referent control values. Eight months after randomization, aldosterone, sST2, TIMP-1, MMP-9, PINP, and PIIINP had decreased more in the sacubitril/valsartan than enalapril group. At baseline, higher values of sST-2, TIMP-1, and PIIINP were associated with higher primary outcome rates. Changes from baseline to 8 months in sST-2 and TIMP-1 were associated with change in outcomes. CONCLUSIONS: Biomarkers associated with profibrotic signaling are altered in HF with reduced ejection fraction, sacubitril/valsartan significantly decreased many of these biomarkers, and these biomarkers have important prognostic value. These findings suggest that sacubitril/valsartan may reduce profibrotic signaling, which may contribute to the improved outcomes. (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure [PARADIGM-HF]; NCT01035255)."}