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

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#benzhydryl-compounds #biomarkers #ferritins #glucosides #heart-failure

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

Docherty et al., 2022 | Circulation | Rct

Citation

Docherty Kieran F, Welsh Paul, ... McMurray John J V. Iron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF. Circulation. 2022-Sep-27;146(13):980-994. doi:10.1161/CIRCULATIONAHA.122.060511

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.

Key Findings

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%

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population iron deficiency
Sample Size 0
Age Range See abstract
Condition deficiency

MeSH Terms

  • Benzhydryl Compounds
  • Biomarkers
  • Ferritins
  • Glucosides
  • Heart Failure
  • Hepcidins
  • Humans
  • Iron
  • Iron Deficiencies
  • Receptors, Erythropoietin
  • Receptors, Transferrin
  • Stroke Volume
  • Transferrins

Evidence Classification

  • Level: Rct
  • Publication Types: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
  • Vertical: iron-heart

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09