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Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure
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–angi...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10192237/ https://www.ncbi.nlm.nih.gov/pubmed/36782339 http://dx.doi.org/10.1002/ehf2.14313 |
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author | Bosch, Agnes Poglitsch, Marko Kannenkeril, Dennis Kolwelter, Julie Striepe, Kristina Ott, Christian Rauh, Manfred Schiffer, Mario Achenbach, Stephan Schmieder, Roland E. |
author_facet | Bosch, Agnes Poglitsch, Marko Kannenkeril, Dennis Kolwelter, Julie Striepe, Kristina Ott, Christian Rauh, Manfred Schiffer, Mario Achenbach, Stephan Schmieder, Roland E. |
author_sort | Bosch, Agnes |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10192237 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101922372023-05-19 Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure Bosch, Agnes Poglitsch, Marko Kannenkeril, Dennis Kolwelter, Julie Striepe, Kristina Ott, Christian Rauh, Manfred Schiffer, Mario Achenbach, Stephan Schmieder, Roland E. ESC Heart Fail Original Articles 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. John Wiley and Sons Inc. 2023-02-13 /pmc/articles/PMC10192237/ /pubmed/36782339 http://dx.doi.org/10.1002/ehf2.14313 Text en © 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Bosch, Agnes Poglitsch, Marko Kannenkeril, Dennis Kolwelter, Julie Striepe, Kristina Ott, Christian Rauh, Manfred Schiffer, Mario Achenbach, Stephan Schmieder, Roland E. Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure |
title | Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure |
title_full | Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure |
title_fullStr | Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure |
title_full_unstemmed | Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure |
title_short | Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure |
title_sort | angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10192237/ https://www.ncbi.nlm.nih.gov/pubmed/36782339 http://dx.doi.org/10.1002/ehf2.14313 |
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