Bosch A, Poglitsch M, Kannenkeril D, Kolwelter J, Striepe K, Ott C, Rauh M, Schiffer M, Achenbach S, Schmieder R (2023)
Publication Type: Journal article
Publication year: 2023
DOI: 10.1002/ehf2.14313
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.
APA:
Bosch, A., Poglitsch, M., Kannenkeril, D., Kolwelter, J., Striepe, K., Ott, C.,... Schmieder, R. (2023). Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure. ESC Heart Failure. https://doi.org/10.1002/ehf2.14313
MLA:
Bosch, Agnes, et al. "Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure." ESC Heart Failure (2023).
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