Iron deficiency in heart failure and effect of dapagliflozin: findings from DAPA-HF

Docherty, K. F. et al. (2022) Iron deficiency in heart failure and effect of dapagliflozin: findings from DAPA-HF. Circulation, 146(13), pp. 980-994. (doi: 10.1161/CIRCULATIONAHA.122.060511) (PMID:35971840) (PMCID:PMC9508991)

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Background: Iron deficiency is common in heart failure and associated with worse outcomes. We examined the prevalence and consequences of iron deficiency in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) and the effect of dapagliflozin on markers of iron metabolism. We also analyzed the effect of dapagliflozin on outcomes, according to iron status at baseline. Methods: Iron deficiency was defined as a ferritin level <100 ng/mL or a transferrin saturation <20% and a ferritin level 100 to 299 ng/mL. Additional biomarkers of iron metabolism, including soluble transferrin receptor, erythropoietin, and hepcidin were measured at baseline and 12 months after randomization. The primary outcome was a composite of worsening heart failure (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death. Results: Of the 4744 patients randomized in DAPA-HF, 3009 had ferritin and transferrin saturation measurements available at baseline, and 1314 of these participants (43.7%) were iron deficient. The rate of the primary outcome was higher in patients with iron deficiency (16.6 per 100 person-years) compared with those without (10.4 per 100 person-years; P<0.0001). The effect of dapagliflozin on the primary outcome was consistent in iron-deficient compared with iron-replete patients (hazard ratio, 0.74 [95% CI, 0.58–0.92] versus 0.81 [95% CI, 0.63–1.03]; P-interaction=0.59). Similar findings were observed for cardiovascular death, heart failure hospitalization, and all-cause mortality. Transferrin saturation, ferritin, and hepcidin were reduced and total iron-binding capacity and soluble transferrin receptor increased with dapagliflozin compared with placebo. Conclusions: Iron deficiency was common in DAPA-HF and associated with worse outcomes. Dapagliflozin appeared to increase iron use but improved outcomes, irrespective of iron status at baseline. Registration: URL:; Unique identifier: NCT03036124.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Docherty, Dr Kieran and Jhund, Professor Pardeep and Sattar, Professor Naveed and Welsh, Professor Paul and McMurray, Professor John and Kober, Professor Lars
Authors: Docherty, K. F., Welsh, P., Verma, S., De Boer, R. A., O'Meara, E., Bengtsson, O., Køber, L., Kosiborod, M. N., Hammarstedt, A., Langkilde, A. M., Lindholm, D., Little, D. J., Sjöstrand, M., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Morrow, D. A., Schou, M., Solomon, S. D., Sattar, N., Jhund, P. S., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Circulation
Publisher:American Heart Association
ISSN (Online):1524-4539
Published Online:16 August 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Circulation 146(13): 980-994
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science