Dapagliflozin's Association With Cardiorenal Outcomes and Apolipoprotein M Levels in HFrEF Patients

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 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.