Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Jun 30;13(1):10591.
doi: 10.1038/s41598-023-37491-5.

Dapagliflozin and short-term changes on circulating antigen carbohydrate 125 in heart failure with reduced ejection fraction

Martina Amiguet #  1 , Patricia Palau #  2 , Eloy Domínguez  1 , Julia Seller  3 , Jose Manuel Garcia Pinilla  4   5 , Rafael de la Espriella  6 , Gema Miñana  6   5 , Alfonso Valle  3 , Juan Sanchis  6   5 , Jose Luis Górriz  7 , Antoni Bayés-Genís  5   8   9 ; DAPA VO2 investigators; Julio Núñez  10   11
Collaborators, Affiliations
Randomized Controlled Trial

Dapagliflozin and short-term changes on circulating antigen carbohydrate 125 in heart failure with reduced ejection fraction

Martina Amiguet et al. Sci Rep. .

Abstract

Circulating antigen carbohydrate 125 (CA125) has emerged as a proxy of fluid overload in heart failure. This study aimed to evaluate the effect of dapagliflozin on short-term CA125 levels in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effects on peak oxygen consumption (peakVO2). This study is a post-hoc sub-analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly assigned to receive either dapagliflozin or placebo to evaluate change in peakVO2 (NCT04197635). We used linear mixed regression analysis to compare changes in the natural logarithm of CA125 (logCA125) and percent changes from baseline (Δ%CA125). We used the "rwrmed" package to perform mediation analyses. CA125 was available in 87 patients (96.7%). LogCA125 significantly decreased in patients on treatment with dapagliflozin [1-month: Δ - 0.18, (CI 95% = - 0.33 to - 0.22) and 3-month: Δ - 0.23, (CI 95% = - 0.38 to - 0.07); omnibus p-value = 0.012]. Δ%CA125 decreased by 18.4% and 31.4% at 1 and 3-month, respectively (omnibus p-value = 0.026). Changes in logCA125 mediated the effect on peakVO2 by 20.4% at 1 month (p < 0.001). We did not find significant changes for natural logarithm of NTproBNP (logNT-proBNP) [1-month: Δ - 0.03, (CI 95% = - 0.23 to 0.17; p = 0.794), and 3-month: Δ 0.73, (CI 95% = - 0.13 to 0.28; p-value 0.489), omnibus p-value = 0.567]. In conclusion, in patients with stable HFrEF, dapagliflozin resulted in a significant reduction in CA125. Dapagliflozin was not associated with short-term changes in natriuretic peptides. These changes mediated the effects on peakVO2.

PubMed Disclaimer

Conflict of interest statement

J.S. reports speaker fees from Astra Zeneca and Boehringer Ingelheim. JMGP reports personal fees from Astra Zeneca and Esteve. JMGP reports personal fees from Astra Zeneca and Esteve. AV reports speaker fees from Astra Zeneca. R.E. reports personal fees from Astra Zeneca, Novartis, Boehringer-Ingelheim, and NovoNordisk. AV reports speaker fees from Astra Zeneca. JS has received speaker fees from Abbott Vascular and Prosmédica. JLG has received fees for participating in advisory boards and educational activities from Astra Zeneca, Boehringer-Ingelheim, NovoNordisk, Bayer, and Novartis. A.B.-G. has lectured and/or participated in advisory boards for Abbott, Astra Zeneca, Boehringer-Ingelheim, Novartis, Roche Diagnostics, and Vifor. J.N. reports personal fees from Astra Zeneca, Novartis, Boehringer-Ingelheim, Eli Lilly, Rovi, NovoNordisk, and Vifor Pharma. Other authors do not have competing interest.

Figures

Figure 1
Figure 1
Changes in logCA125 (a) and percentage changes in CA125 (b) between dapagliflozin and placebo at 1-month and 3-month. CA125, antigen carbohydrate 125, logCA125, the natural logarithm of antigen carbohydrate 125.
Figure 2
Figure 2
Changes in logNT-proBNP (a) and percentage changes in NT-proBNP (b) between dapagliflozin and placebo at 1-month and 3-month. LogNT-proBNP, the natural logarithm of N-terminal prohormone of brain natriuretic peptide; NT-proBNP, N-terminal prohormone of brain natriuretic peptide.
Figure 3
Figure 3
Changes in logCA125 (a) and logNT-proBNP (b) stratified across baseline values at 1-month and 3-month. CA125, antigen carbohydrate 125, logCA125, the natural logarithm of antigen carbohydrate 125; logNT-proBNP, the natural logarithm of N-terminal prohormone of brain natriuretic peptide; NT-proBNP, N-terminal prohormone of brain natriuretic peptide.
See this image and copyright information in PMC

References

    1. McDonagh TA, et al. ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 2021;42:3599–3726. doi: 10.1093/eurheartj/ehab368. - DOI - PubMed
    1. Bjornstad P, et al. The potential roles of osmotic and nonosmotic sodium handling in mediating the effects of sodium-glucose cotransporter 2 inhibitors on heart failure. J. Cardiac. Fail. 2021;27:1447–1455. doi: 10.1016/j.cardfail.2021.07.003. - DOI - PMC - PubMed
    1. Boorsma EM, et al. Effects of empagliflozin on renal sodium and glucose handling in patients with acute heart failure. Eur. J. Heart Fail. 2021;23:68–78. doi: 10.1002/ejhf.2066. - DOI - PMC - PubMed
    1. Núñez J, et al. Antigen carbohydrate 125 as a biomarker in heart failure: A narrative review. Eur. J. Heart Fail. 2021;23:1445–1457. doi: 10.1002/ejhf.2295. - DOI - PubMed
    1. Kumric M, et al. Carbohydrate antigen 125: A biomarker at the Crossroads of congestion and inflammation in heart failure. Card. Fail. Rev. 2021;7:e19. doi: 10.15420/cfr.2021.22. - DOI - PMC - PubMed

Publication types

Associated data

LinkOut - more resources