Brief Report
Short-term Changes in Hemoglobin and Changes in Functional Status, Quality of Life and Natriuretic Peptides After Initiation of Dapagliflozin in Heart Failure With Reduced Ejection Fraction

https://doi.org/10.1016/j.cardfail.2023.02.008Get rights and content

Highlights

  • In this subanalysis of the DAPA-VO2 randomized clinical trial, dapagliflozin lead to a significant short-term increases in hemoglobin levels.

  • Short-term hemoglobin changes were associated with the magnitude of between-treatment differences (dapagliflozin vs placebo) in maximal functional capacity, quality of life and natriuretic peptides.

  • The magnitude of hemoglobin increase emerges as a simple and widely available parameter for monitoring SGLT2i responses.

ABSTRACT

Background

We aimed to evaluate the effect of dapagliflozin on short-term changes in hemoglobin in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effect of dapagliflozin on functional capacity, quality of life and NT-proBNP levels.

Methods

This is an exploratory analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly allocated to dapagliflozin or placebo to evaluate short-term changes in peak oxygen consumption (peak VO2) (NCT04197635). This substudy evaluated 1- and 3-month changes in hemoglobin levels and whether these changes mediated the effects of dapagliflozin on peak VO2, Minnesota Living-With-Heart-Failure test (MLHFQ) and NT-proBNP levels.

Results

At baseline, mean hemoglobin levels were 14.3 ± 1.7 g/dL. Hemoglobin levels significantly increased in those taking dapagliflozin (1 month: + 0.45 g/dL (P = 0.037) and 3 months:+ 0.55 g/dL (P = 0.012)]. Changes in hemoglobin levels positively mediated the changes in peak VO2 at 3 months (59.5%; P < 0.001). Changes in hemoglobin levels significantly mediated the effect of dapagliflozin in the MLHFQ at 3 months (-53.2% and -48.7%; P = 0.017) and NT-proBNP levels at 1 and 3 months (-68.0%; P = 0.048 and -62.7%; P = 0.029, respectively).

Conclusions

In patients with stable HFrEF, dapagliflozin caused a short-term increase in hemoglobin levels, identifying patients with greater improvements in maximal functional capacity, quality of life and reduction of NT-proBNP levels.

Section snippets

Methods

This study was an exploratory analysis of the DAPA-VO2 randomized clinical trial.2 The study was an investigator-initiated, multicenter, double-blind, randomized clinical trial designed to evaluate the effect of dapagliflozin on maximal functional capacity as assessed by peak VO2 in 90 patients with stable, chronic HF and left ventricular ejection fraction (LVEF) ≤ 40%. Patients were randomized 1:1 to receive either dapagliflozin or a placebo. Maximal functional capacity was evaluated at 3 time

Results

At baseline, hemoglobin levels were available for all patients. The mean age was 67.1 ± 10.7 years, 69 (76.7%) were men, and 80 (88.9%) were in stable New York Heart Association class II. The baseline mean values and standard deviation (SD) of hemoglobin and peak VO2 were 14.3 ± 1.7 g/dL and 13.2 ± 3.5 mL/kg/min, respectively. The median (P 25%–75%) of MLHFQ and NT-proBNP levels were 19 (10–33) and 1221 pg/mL (889–2100), respectively. There were no differences in baseline characteristics across

Discussion

In this exploratory analysis, we confirm prior findings that indicated a significant short-term increase in hemoglobin levels after initiation of SGLT2is. More interesting, we found that the magnitude of this increment mediated the improvement in short-term maximal functional capacity, quality of life and natriuretic peptides.

Several factors may explain the rise in hemoglobin levels following SGLT2is and their relationship with the clinical response. A short-term increase in hemoglobin and

Conclusion

In patients with stable HFrEF, dapagliflozin led to a significant short-term increase in hemoglobin levels. Changes in hemoglobin mediated the short-term effect on surrogates of the efficacy, such as maximal functional capacity, quality of life and natriuretic peptides.

Disclosures

PP has received fees for participating in educational activities from Servier. MA reports personal fees from Astra Zeneca, Novartis, Boehringer-Ingelheim, Eli Lilly, and Pfizer. JS reports speaker fees from Astra Zeneca and Boehringer Ingelheim. JMGP reports personal fees from Astra Zeneca and Esteve. AV reports speaker fees from Astra Zeneca. RE reports personal fees from Astra Zeneca, Novartis, Boehringer-Ingelheim, and NovoNordisk. JS has received speaker fees from Abbott Vascular and

Acknowledgments

The authors acknowledge all the DAPA-VO2 investigators: Jose Civera, Adriana Conesa, Rim Zakarne, Clara Jiménez Rubio, Alejandro I. Pérez Cabeza, Arancha Díaz Expósito, José David Martínez Carmona, Manuel Luna Mo rales, Francisco J. Zafra Sánchez, Ángel Montiel Trujillo, and Herminio Morillas Climent.

Authors’ Contributions

Miguel Lorenzo, Julio Núñez, Patricia Palau, Martina Amiguet, and Gema Miñana postulated the hypothesis, wrote the proposal, enrolled patients, and drafted the manuscript. Patricia Palau, Martina Amiguet, Julia Seller, Sandra Villar, Jose Manuel Garcia Pinilla, Jose Luis Górriz, Alfonso Valle, Rafael de la Espriella, and Eloy Domínguez were in charge of the main study protocol, conducted the cardiopulmonary exercise test, echocardiography, follow-up clinical visits, and participated in

Funding

This work was supported in part by an unrestricted grant from Astra Zeneca (ESR-17-13447), Unidad de Investigación Clínica y Ensayos Clínicos INCLIVA Health Research Institute, Spanish Clinical Research Network (SCReN; PT17/0017/0003 y PT20/00100), and CIBER Cardiovascular [grant numbers 16/11/00420, 16/11/00403, and 16/11/00486].

References (8)

There are more references available in the full text version of this article.

Cited by (2)

Both authors contributed equally to this study.

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DAPA-VO2 Investigators: Patricia Palau, Martina Amiguet, Eloy Domínguez, Clara Sastre, Anna Mollar, Julia Seller, Jose Manuel Garcia Pinilla, Ainoha Larumbe, Alfonso Valle, Juan Jose Gómez Doblas, Rafael de la Espriella, Gema Miñana, Sandra Villar, Ainhoa Robles Mezcua, Enrique Santas, Vicent Bodí, Juan Sanchis, Domingo Pascual-Figal, Jose Luis Górriz, Antonio Baýes-Genís, Jose Civera, Adriana Conesa, Rim Zakarne, Clara Jiménez Rubio, Alejandro I. Pérez Cabeza, Arancha Díaz Expósito, José David Martínez Carmona, Manuel Luna Morales, Francisco J. Zafra Sánchez, Ángel Montiel Trujillo, Herminio Morillas Climent, and Julio Núñez.

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