Iron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF

Kieran F Docherty, Paul Welsh, Subodh Verma, Rudolf A De Boer, Eileen O'Meara, Olof Bengtsson, Lars Køber, Mikhail N Kosiborod, Ann Hammarstedt, Anna Maria Langkilde, Daniel Lindholm, Dustin J Little, Mikaela Sjöstrand, Felipe A Martinez, Piotr Ponikowski, Marc S Sabatine, David A Morrow, Morten Schou, Scott D Solomon, Naveed SattarPardeep S Jhund, John J V McMurray, DAPA-HF Investigators and Committees

75 Citationer (Scopus)

Abstract

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: https://www.

CLINICALTRIALS: gov; Unique identifier: NCT03036124.

OriginalsprogEngelsk
TidsskriftCirculation
Vol/bind146
Udgave nummer13
Sider (fra-til)980-994
Antal sider15
ISSN0009-7322
DOI
StatusUdgivet - 27 sep. 2022

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