Iron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF
TLDR
In this article , the authors examined the prevalence and consequences of iron deficiency in the DAPA-HF trial and the effect of dapagliflozin on markers of iron metabolism.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. read more
Citations
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Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial
TL;DR: The IRONMAN trial as discussed by the authors evaluated the longer-term effects of intravenous ferric derisomaltose on cardiovascular events in patients with heart failure and found that intravenous carboxymaltose administration improves quality of life and exercise capacity in the short-term and reduces hospital admissions for heart failure up to 1 year.
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Potential Interactions When Prescribing SGLT2 Inhibitors and Intravenous Iron in Combination in Heart Failure.
TL;DR: In patients with heart failure, sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to decrease hepcidin and ferritin and increase transferrin receptor protein, changes that are typically indicative of worsening absolute iron deficiency as discussed by the authors .
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SGLT2 inhibitors: role in protective reprogramming of cardiac nutrient transport and metabolism
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How can sodium–glucose cotransporter 2 inhibitors stimulate erythrocytosis in patients who are iron‐deficient? Implications for understanding iron homeostasis in heart failure
TL;DR: In this paper , SGLT2 inhibitors are shown to increase the levels of cytosolic Fe2+ available to mitochondria, thus enabling the synthesis of heme (in erythroid precursors) and ATP (in cardiomyocytes).
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Effects of empagliflozin on erythropoiesis in heart failure: data from the Empire HF trial
Camilla Fuchs Andersen,Massar Omar,Andreas Glenthøj,Daniel El Fassi,Holger Jon Møller,Jørgen Anders Lindholm Kurtzhals,Bjarne Styrishave,Caroline Kistorp,Christian Tuxen,Mikael Kjær Poulsen,Jens Faber,Lars Køber,Finn Gustafsson,Jacob E. Møller,Morten Schou,Jesper Jensen +15 more
TL;DR: The present analyses suggest that empagliflozin increases erythropoiesis and induces changes in iron metabolism in a population of patients with HFrEF, primarily without diabetes.
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Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
John J.V. McMurray,Scott D. Solomon,Silvio E. Inzucchi,Lars Køber,Mikhail Kosiborod,Felipe Martinez,Piotr Ponikowski,Marc S. Sabatine,Marc S. Sabatine,Inder S. Anand,Jan Bělohlávek,Michael Böhm,Chern-En Chiang,Chern-En Chiang,Vijay K. Chopra,Rudolf A. de Boer,Akshay S. Desai,Mirta Diez,Jarosław Drożdż,Andrej Dukát,Junbo Ge,Jonathan G. Howlett,Jonathan G. Howlett,Tzvetana Katova,Masafumi Kitakaze,Charlotta Ljungman,Béla Merkely,Jose C. Nicolau,Eileen O'Meara,Mark C. Petrie,Pham Nguyen Vinh,Morten Schou,Tereshchenko Sn,Subodh Verma,Claes Held,David L. DeMets,Kieran F. Docherty,Pardeep S. Jhund,Olof Bengtsson,Mikaela Sjöstrand,AM Langkilde +40 more
TL;DR: Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than amongThose who received placebo, regardless of the presence or absence of diabetes.
Journal ArticleDOI
Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency.
Stefan D. Anker,Josep Comin Colet,Gerasimos Filippatos,Ronnie Willenheimer,Kenneth Dickstein,Helmut Drexler,Thomas F. Lüscher,Boris Bart,Waldemar Banasiak,Joanna Niegowska,Bridget Anne Kirwan,Claudio Mori,Barbara von Eisenhart Rothe,Stuart J. Pocock,Philip A. Poole-Wilson,Piotr Ponikowski +15 more
TL;DR: Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency, with or without anemia, improves symptoms, functional capacity, and quality of life; the side-effect profile is acceptable.
Journal ArticleDOI
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
Paul A. Heidenreich,Biykem Bozkurt,David Aguilar,Larry A. Allen,Joni J. Byun,Monica Colvin,Anita Deswal,Mark H. Drazner,Shannon M. Dunlay,Linda R. Evers,James C. Fang,Savitri Fedson,Gregg C. Fonarow,Salim S. Hayek,Adrian F. Hernandez,Prateeti Khazanie,Michelle M. Kittleson,Christopher S. Lee,Mark S. Link,Carmelo A. Milano,Lorraine C. Nnacheta,Alexander T. Sandhu,Lynne W. Stevenson,Orly Vardeny,Amanda R. Vest,Clyde W. Yancy +25 more
TL;DR: The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" as discussed by the authors provides patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure.
Journal ArticleDOI
Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes.
TL;DR: Dapagliflozin and hydrochlorothiazide effects on 24‐h blood pressure, body weight, plasma volume and glomerular filtration rate are compared to investigate whether the parallel occurring sodium loss would have diuretic‐like physiologic effects.
Journal ArticleDOI
Iron deficiency: an ominous sign in patients with systolic chronic heart failure
Ewa A. Jankowska,Piotr Rozentryt,Agnieszka Witkowska,Jolanta Nowak,Oliver Hartmann,Beata Ponikowska,Ludmila Borodulin-Nadzieja,Waldemar Banasiak,Lech Poloński,Gerasimos Filippatos,John J.V. McMurray,Stefan D. Anker,Piotr Ponikowski +12 more
TL;DR: In patients with systolic CHF, ID is common and constitutes a strong, independent predictor of unfavourable outcome, and iron supplementation may be considered as a therapeutic approach in these patients to improve prognosis.