Iron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF. Issue 13 (16th August 2022)

• Record Type: Journal Article
• Authors: Docherty, Kieran F.; Welsh, Paul; Verma, Subodh; De Boer, Rudolf A.; O'Meara, Eileen; Bengtsson, Olof; Køber, Lars; Kosiborod, Mikhail N.; Hammarstedt, Ann; Langkilde, Anna Maria; Lindholm, Daniel; Little, Dustin J.; Sjöstrand, Mikaela; Martinez, Felipe A.; Ponikowski, Piotr; Sabatine, Marc S.; Morrow, David A.; Schou, Morten; Solomon, Scott D.; Sattar, Naveed; Jhund, Pardeep S.; McMurray, John J.V.
• Is Part Of: Circulation. Volume 146:Issue 13(2022)
• Page Start: 980
• Page End: 994
• Publication Date: 2022-08-16
• Subjects: anemia -- erythropoiesis -- ferritin -- heart failure -- hepcidin -- iron -- sodium-glucose cotransporter 2 inhibitor -- transferrin; Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.122.060511
• Languages: English
• ISSNs: 0009-7322

Abstract

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.