Dapagliflozin's Association With Cardiorenal Outcomes and Apolipoprotein M Levels in HFrEF Patients : Insights From DEFINE-HF
(2025) In JACC: Advances 4(6 Pt 2). p.1-12- Abstract
BACKGROUND: Apolipoprotein M (ApoM) is associated with lower mortality in heart failure (HF) patients and protects against cardiac and kidney injury in mice.
OBJECTIVES: The authors investigated dapagliflozin's cardiorenal effects by studying its association with ApoM in patients with HF with reduced ejection fraction.
METHODS: We performed a secondary analysis of DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients with HF with Reduced Ejection Fraction) to assess dapagliflozin's effects on ApoM, N-terminal pro B-type natriuretic peptide (NT-proBNP), and urine albumin-creatinine ratio (UACR) changes from baseline to 12 weeks.
RESULTS: Of 263 randomized patients, 236 had ApoM... (More)
BACKGROUND: Apolipoprotein M (ApoM) is associated with lower mortality in heart failure (HF) patients and protects against cardiac and kidney injury in mice.
OBJECTIVES: The authors investigated dapagliflozin's cardiorenal effects by studying its association with ApoM in patients with HF with reduced ejection fraction.
METHODS: We performed a secondary analysis of DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients with HF with Reduced Ejection Fraction) to assess dapagliflozin's effects on ApoM, N-terminal pro B-type natriuretic peptide (NT-proBNP), and urine albumin-creatinine ratio (UACR) changes from baseline to 12 weeks.
RESULTS: Of 263 randomized patients, 236 had ApoM values at baseline (mean 0.641 ± 0.181 μM) and 12 weeks. Dapagliflozin did not significantly affect ApoM vs placebo. However, each 0.1 μM increase in ApoM was associated with a significant decrease in log-transformed NT-proBNP overall (β = -0.11, P = 0.006), particularly in dapagliflozin-treated patients (β = -0.19, P < 0.001; P interaction = 0.025). The inverse relationship between ApoM and NT-proBNP varied by changes in UACR. Dapagliflozin-treated patients with reduced UACR at 12 weeks (n = 53, 22%) experienced a mean NT-proBNP reduction of -0.28 per 0.1 μM increase in ApoM (P < 0.001), compared to a smaller reduction in those without UACR change (-0.07, P = 0.47). Placebo-treated patients with reduced UACR over 12 weeks did not show significant NT-proBNP changes (β = -0.17, P = 0.11).
CONCLUSIONS: Dapagliflozin did not significantly alter ApoM overall; however, an inverse association between ApoM and NT-proBNP was observed in dapagliflozin-treated patients with albuminuria. While some NT-proBNP reductions were seen in the placebo group, the significant interaction with treatment allocation suggests a potential dapagliflozin-mediated effect.
(Less)
- author
- author collaboration
- organization
- publishing date
- 2025-06
- type
- Contribution to journal
- publication status
- published
- subject
- in
- JACC: Advances
- volume
- 4
- issue
- 6 Pt 2
- article number
- 101800
- pages
- 1 - 12
- publisher
- American College of Cardiology
- external identifiers
-
- scopus:105007814609
- pmid:40579063
- ISSN
- 2772-963X
- DOI
- 10.1016/j.jacadv.2025.101800
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
- id
- d18fe4a1-6a44-40c3-90ca-9846d17c3823
- date added to LUP
- 2025-06-30 07:51:49
- date last changed
- 2025-07-01 04:01:16
@article{d18fe4a1-6a44-40c3-90ca-9846d17c3823,
abstract = {{<p>BACKGROUND: Apolipoprotein M (ApoM) is associated with lower mortality in heart failure (HF) patients and protects against cardiac and kidney injury in mice.</p><p>OBJECTIVES: The authors investigated dapagliflozin's cardiorenal effects by studying its association with ApoM in patients with HF with reduced ejection fraction.</p><p>METHODS: We performed a secondary analysis of DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients with HF with Reduced Ejection Fraction) to assess dapagliflozin's effects on ApoM, N-terminal pro B-type natriuretic peptide (NT-proBNP), and urine albumin-creatinine ratio (UACR) changes from baseline to 12 weeks.</p><p>RESULTS: Of 263 randomized patients, 236 had ApoM values at baseline (mean 0.641 ± 0.181 μM) and 12 weeks. Dapagliflozin did not significantly affect ApoM vs placebo. However, each 0.1 μM increase in ApoM was associated with a significant decrease in log-transformed NT-proBNP overall (β = -0.11, P = 0.006), particularly in dapagliflozin-treated patients (β = -0.19, P < 0.001; P interaction = 0.025). The inverse relationship between ApoM and NT-proBNP varied by changes in UACR. Dapagliflozin-treated patients with reduced UACR at 12 weeks (n = 53, 22%) experienced a mean NT-proBNP reduction of -0.28 per 0.1 μM increase in ApoM (P < 0.001), compared to a smaller reduction in those without UACR change (-0.07, P = 0.47). Placebo-treated patients with reduced UACR over 12 weeks did not show significant NT-proBNP changes (β = -0.17, P = 0.11).</p><p>CONCLUSIONS: Dapagliflozin did not significantly alter ApoM overall; however, an inverse association between ApoM and NT-proBNP was observed in dapagliflozin-treated patients with albuminuria. While some NT-proBNP reductions were seen in the placebo group, the significant interaction with treatment allocation suggests a potential dapagliflozin-mediated effect.</p>}},
author = {{Sauer, Andrew J and Chang, Joycie and Fu, Zhuxuan and Valenzuela Ripoll, Carla and Cho, Yoonje and Guo, Zhen and Jones, Philip and Selvaraj, Senthil and Windsor, Sheryl L and Husain, Mansoor and Inzucchi, Silvio E and McGuire, Darren K and Pitt, Bertram and Scirica, Benjamin M and Austin, Bethany A and Umpierrez, Guillermo and Tran, Sinh and Dahlbäck, Björn and Javaheri, Ali and Kosiborod, Mikhail N}},
issn = {{2772-963X}},
language = {{eng}},
number = {{6 Pt 2}},
pages = {{1--12}},
publisher = {{American College of Cardiology}},
series = {{JACC: Advances}},
title = {{Dapagliflozin's Association With Cardiorenal Outcomes and Apolipoprotein M Levels in HFrEF Patients : Insights From DEFINE-HF}},
url = {{http://dx.doi.org/10.1016/j.jacadv.2025.101800}},
doi = {{10.1016/j.jacadv.2025.101800}},
volume = {{4}},
year = {{2025}},
}