Early glomerular filtration rate decline is associated with hemoglobin rise following dapagliflozin initiation in heart failure with reduced ejection fraction.

INTRODUCTION AND OBJECTIVES: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce short-term changes in renal function and hemoglobin. Their pathophysiology is incompletely understood. We aimed to evaluate the relationship between 1- and 3-month estimated glomerular filtration rate (eGFR) and hemoglobin changes following initiation of dapagliflozin in patients with stable heart failure with reduced ejection fraction (HFrEF).

METHODS: This is a post hoc analysis of a randomized clinical trial that evaluated the effect of dapagliflozin on 1- and 3-month peak oxygen consumption in outpatients with stable HFrEF (DAPA-VO2 trial, NCT04197635). We used linear mixed regression analysis to assess the relationship between eGFR and hemoglobin changes across treatment arms.

RESULTS: A total of 87 patients were evaluated in this substudy. The mean age was 67.0 ± 10.5 years, and 21 (24.1%) were women. The mean baseline eGFR and hemoglobin were 66.9 ± 20.7 mL/min/1.73m2 and 14.3 ± 1.7 g/dL, respectively. Compared with placebo, eGFR did not significantly change at either time points in the dapagliflozin group, but hemoglobin significantly increased at 1 and 3 months. At 1 month, the hemoglobin increase was related to decreases in eGFR only in the dapagliflozin arm (P < .001). At 3 months, there was no significant association in either treatment arms (P = .123). Changes in eGFR were not associated with changes in peak oxygen consumption, quality of life, or natriuretic peptides.

CONCLUSIONS: In patients with stable HFrEF, 1-month changes in eGFR induced by dapagliflozin are inversely related to changes in hemoglobin. This association was no longer significant at 3 months.