{"id":"cc5cc46c0c36","type":"article","url":"https://hartvaat.nl/2020/08/04/sacubitril-valsartan-en-ecm-biomarkers-bij-hfpef-paragon-hf/","title":"Sacubitril/valsartan en ECM-biomarkers bij HFpEF: PARAGON-HF","title_en":"Effect of Sacubitril/Valsartan on Biomarkers of Extracellular Matrix Regulation in Patients With HFpEF.","category":"hartfalen","category_label":"Hartfalen","professions":["cardioloog"],"tags":["answer-hf","sacubitril-valsartan"],"journal":"Journal of the American College of Cardiology","doi":"10.1016/j.jacc.2020.05.072","source_url":"https://doi.org/10.1016/j.jacc.2020.05.072","authors":["Jonathan W Cunningham","Brian L Claggett","Eileen O'Meara","Margaret F Prescott","Marc A Pfeffer","Sanjiv J Shah","Margaret M Redfield","Faiez Zannad","Lu-May Chiang","Adel R Rizkala","Victor C Shi","Martin P Lefkowitz","Jean Rouleau","John J V McMurray","Scott D Solomon","Michael R Zile"],"significance":5,"published":"2020-08-04","source_date":"2020-08-04","image":"","kennis":["https://hartvaat.nl/kennis/farmacologie/arni-farmacologie/"],"congress":"","summary_en":"This PARAGON-HF analysis showed that sacubitril-valsartan reduces biomarkers of extracellular matrix regulation in HFpEF, providing evidence of anti-fibrotic effects in the preserved ejection fraction population.","created":"2026-07-03T10:28:42Z","updated":"2026-07-03T13:27:52Z","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":"PARAGON-HF analyse naar het effect van sacubitril/valsartan op biomarkers van extracellulaire matrixregulatie bij HFpEF.","abstract_original":"BACKGROUND: Myocardial fibrosis may contribute to the pathophysiology of heart failure with preserved ejection fraction. Given the biochemical targets of sacubitril/valsartan, this study hypothesized that circulating biomarkers reflecting the mechanisms that determine extracellular matrix homeostasis are altered by sacubitril/valsartan compared with valsartan alone. OBJECTIVES: This study investigated the effects of sacubitril/valsartan on biomarkers of extracellular matrix homeostasis and the association between biomarkers and the primary endpoint (total heart failure hospitalizations and cardiovascular death). METHODS: N-terminal propeptide of collagen I and III, tissue inhibitor of matrix metalloproteinase 1, carboxyl-terminal telopeptide of collagen type I, and soluble ST2 were measured at baseline (n = 1,135) and 16 (n = 1,113) and 48 weeks (n = 1,016) after randomization. The effects of sacubitril/valsartan on these biomarkers were compared with those of valsartan alone. Baseline biomarker values and changes from baseline to 16 weeks were related to primary endpoint. RESULTS: At baseline, all 5 biomarkers were higher than published referent control values. Sixteen weeks after randomization, sacubitril/valsartan decreased tissue inhibitor of matrix metalloproteinase 1 by 8% (95% confidence interval [CI]: 6% to 10%; p < 0.001), soluble ST2 by 4% (95% CI: 1% to 7%; p = 0.002), and N-terminal propeptide of collagen III by 3% (95% CI: 0% to 6%; p = 0.04) and increased carboxyl-terminal telopeptide of collagen type I by 4% (95% CI: 1% to 8%; p = 0.02) compared with valsartan alone, consistently in men and women and patients with left ventricular ejection fraction above or below the median of 57%. Higher levels of tissue inhibitor of matrix metalloproteinase 1 and soluble ST2 at baseline and increases in these markers at 16 weeks were associated with higher primary endpoint event rates. CONCLUSIONS: Biomarkers reflecting extracellular matrix homeostasis are elevated in heart failure with preserved ejection fraction, favorably altered by sacubitril/valsartan, and have important prognostic value. (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)."}