Short-Term Changes in Peak VO2 After Initiation of Dapagliflozin in Heart Failure Across Iron Status.

Abstract

BACKGROUND:

Some studies have indicated that sodium-glucose cotransporter-2 (SGLT2) inhibitors promote an increase in cell iron use.

OBJECTIVES:

The aim of this study was to examine, in patients with stable heart failure with reduced left ventricular ejection fraction (HFrEF), the effect of dapagliflozin on ferrokinetic parameters and whether short-term changes in peak oxygen consumption (Vo2) after dapagliflozin treatment are influenced by baseline and serial ferrokinetic status.

METHODS:

This was an exploratory analysis of a randomized, double-blind clinical trial that evaluated the effect of dapagliflozin vs placebo on peak Vo2 in patients with HFrEF (NCT04197635) and included 76 of the 90 patients initially enrolled in the trial. Changes in peak Vo2 at 1 and 3 months were explored according to baseline and longitudinal ferrokinetic parameters (natural logarithm [ln] ferritin, transferrin saturation index [TSAT], soluble transferrin receptor, and hepcidin). Linear mixed-effect regression was used for the analyses.

RESULTS:

Compared with placebo, dapagliflozin led to a significant decrease in 3-month ln ferritin (P = 0.040) and an increase in 1-month ln soluble transferrin receptor (P = 0.023). Between-treatment comparisons revealed a stepwise increase in peak Vo2 in the dapagliflozin group at 1 and 3 months, which was especially apparent at lower baseline values of TSAT and ferritin (P < 0.05). Lower time-varying values of TSAT (1 and 3 months) also identified patients with greater improvements in peak Vo2.

CONCLUSIONS:

In patients with stable HFrEF, treatment with dapagliflozin resulted in short-term increases in peak Vo2, which were most marked in patients with surrogates of greater iron deficiency at baseline and during treatment. (Short-Term Effects of Dapagliflozin on Peak Vo2 in HFrEF [DAPA-VO2]; NCT04197635).

• Authors: Miguel Lorenzo, Conxita Jacobs-Cachá, Patricia Palau, Martina Amiguet, Julia Seller, Eduardo Núñez, Rafael de la Espriella, Jose Luis Górriz, Gema Miñana, Juan Sanchis, Antoni Bayés-Genis, Maria José Soler, Milton Packer, Julio Núñez, DAPA-VO2 Investigators
• Journal: JACC. Heart failure (JACC Heart Fail) Vol. 11 Issue 11 Pg. 1611-1622 (11 2023) ISSN: 2213-1787 [Electronic] United States
• PMID: 37676213 (Publication Type: Randomized Controlled Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Iron
• dapagliflozin
• Ferritins
• Receptors, Transferrin

Topics

• Humans
• Stroke Volume
• Ventricular Function, Left
• Heart Failure (drug therapy)
• Iron
• Treatment Outcome
• Ferritins
• Receptors, Transferrin (therapeutic use)