{"id":"226eaba03894","type":"article","url":"https://hartvaat.nl/2023/06/01/angiotensinepathways-onder-empagliflozine-bij-chronisch-hartfalen/","title":"Angiotensinepathways onder empagliflozine bij chronisch hartfalen","title_en":"Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure.","category":"hartfalen","category_label":"Hartfalen","professions":["cardioloog","internist"],"tags":["acuut-hartfalen","bisoprolol","bloeddrukbehandeling","dapagliflozine","empagliflozine","emperor-trials","hfref","sacubitril-valsartan"],"journal":"ESC heart failure","doi":"10.1002/ehf2.14313","source_url":"https://doi.org/10.1002/ehf2.14313","authors":["Agnes Bosch","Marko Poglitsch","Dennis Kannenkeril","Julie Kolwelter","Kristina Striepe","Christian Ott","Manfred Rauh","Mario Schiffer","Stephan Achenbach","Roland E Schmieder"],"significance":5,"published":"2023-06-01","source_date":"2023-06-01","image":"","kennis":["https://hartvaat.nl/kennis/farmacologie/aldosteron-en-raas-farmacologie/","https://hartvaat.nl/kennis/farmacologie/lisdiuretica-furosemide-bumetanide/"],"congress":"","summary_en":"This study characterized the effects of empagliflozin on angiotensin pathway components in chronic heart failure, showing that SGLT2 inhibition modulates RAAS activation beyond its diuretic-natriuretic effects.","created":"2026-07-03T10:30:23Z","updated":"2026-07-03T18:39:02Z","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 onderzocht het effect van empagliflozine op het renine-angiotensinesysteem bij chronisch hartfalen. SGLT2-remming beïnvloedde de angiotensinebalans, wat bijdraagt aan het begrip van het pleiotrope werkingsmechanisme.","abstract_original":"AIMS: Large outcome studies demonstrated a reduction of heart failure hospitalization or cardiovascular death in patients with chronic heart failure (CHF). The renin-angiotensin system (RAS) is a key player in fluid and sodium regulation. The classic angiotensin-converting enzyme-angiotensin II-angiotensin-1 receptor axis (Ang I-ACE-Ang II receptor axis) is predominantly angiotensin II (Ang-II) induced and promotes vasoconstriction. In contrast, the angiotensin-converting-enzyme-2-angiotensin-(1-7)-Mas axis (Mas-axis) is mediated by the metabolites angiotensin-1-7 (Ang-(1-7)) and angtiotensin-1-5 (Ang-(1-5)) and exerts cardioprotective effects. METHODS: We previously investigated the effect of empagliflozin on the systemic haemodynamic in patients with stable CHF (NYHA II-III) in a randomized placebo-controlled clinical trial 'Analysing the Effect of Empagliflozin on Reduction of Tissue Sodium Content in Patients With Chronic Heart Failure (ELSI)'. In a post hoc analysis, we now analysed whether empagliflozin has an effect on the RAS by measuring detailed RAS profiles (LC-MS/MS-based approach) in 72 patients from ELSI. We compared RAS parameters after 1-month and 3-months treatment with empagliflozin or placebo to baseline. The secondary goal was to analyse whether the effect of empagliflozin on RAS parameters was dependent on angiotensin-receptor-blocking (ARB) or angiotensin-converting-enzyme-inhibitor (ACEI) co-medication. RESULTS: Empagliflozin medication induced a significant rise in Ang-II [68.5 pmol/L (21.3-324.2) vs. 131.5 pmol/L (34.9-564.0), P = 0.001], angiotensin-I (Ang-I) [78.7 pmol/L (21.5-236.6) vs. 125.9 pmol/L (52.6-512.9), P < 0.001], Ang-(1-7) [3.0 pmol/L (3.0-15.0) vs. 10.1 pmol/L (3.0-31.3), P = 0.006], and Ang-(1-5) [5.4 pmol/L (2.0-22.9) vs. 9.9 pmol/L (2.8-36.4), P = 0.004], which was not observed in the placebo group (baseline to 3-months treatment). A significant rise in Ang-II (206.4 pmol/L (64.2-750.6) vs. 568.2 pmol/L (164.7-1616.4), P = 0.001), Ang-(1-7) (3.0 pmol/L (3.0-14.1) vs. 15.0 pmol/L (3.0-31.3), P = 0.017), and Ang-(1-5) [12.2 pmol/L (3.8-46.6) vs. 36.4 pmol/L (11.1-90.7), P = 0.001] under empagliflozin treatment was only seen in the subgroup of patients with ARB co-medication, whereas no change of Ang-II (16.7 pmol/L (2.0-60.8) vs. 26.4 pmol/L (10.7-63.4), P = 0.469), Ang-(1-7) (6.6 pmol/L (3.0-20.7) vs. 10.5 pmol/L (3.0-50.5), P = 0.221), and Ang-(1-5) (2.7 pmol/L (2.0-8.4) vs. 2.8 pmol/L (2.0-6.9), P = 0.851) was observed in patients with empagliflozin that were on ACEI co-medication (baseline to 3-months treatment). CONCLUSIONS: Our data indicate that empagliflozin might lead to an activation of both the Ang I-ACE-Ang II receptor axis and the Mas-axis pathway. Activation of the Ang I-ACE-Ang II receptor axis and the protective Mas-axis pathway after initiating treatment with empagliflozin was only seen in patients with ARB co-medication, in contrast to co-medication with ACEI."}