Scientific Sessions 2024  /  Cracking Comorbidities and Complications in Heart Failure  /  The relationships between circulating biomarkers of iron deficiency and outcomes in patients with heart failure and reduced ejection fraction: insights from DAPA-HF.
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American Heart Association

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Final ID: Su2162

The relationships between circulating biomarkers of iron deficiency and outcomes in patients with heart failure and reduced ejection fraction: insights from DAPA-HF.

Abstract Body (Do not enter title and authors here): Background: In patients with HFrEF, the guideline definition of iron deficiency (ID) uses both ferritin and transferrin saturation (TSAT) levels. However, observational studies and subgroup analyses of randomized controlled trials show that TSAT alone, or alternative biomarkers of ID, may better predict mortality and response to intravenous (iv) iron.

Goal: Examine the relationships between circulating biomarkers and alternative ID definitions and outcomes in patients with HFrEF in DAPA-HF.

Methods: Key inclusion criteria were: 1) NYHA class II-IV, 2) LVEF ≤40%, 3) elevated plasma NT-proBNP and 4) eGFR ≥30 ml/min/1.73m2. The primary outcome was a composite of a worsening HF event (HF hospitalization or an urgent HF visit requiring iv therapy) or cardiovascular death. Iron biomarkers were measured before randomization. The current guideline-recommended definition of ID is ferritin <100ng/mL or TSAT <20% and ferritin 100–299ng/mL. Alternative definitions examined were: iron ≤13umol/L, TSAT<20% (regardless of ferritin), and serum transferrin receptor (sTFR) >4.70mg/L (males) and >4.59mg/L (females).

Results: Of the 4744 patients randomized, 2840 (60%) had ferritin, TSAT, iron and sTFR measured at baseline. Of these, 1228 (43%) had guideline-defined ID (374 [30%] based on ferritin <100ng/mL alone); 857 (70%) had ferritin <100ng/mL, 854 (70%) TSAT <20%, 853 (69%) iron ≤13umol/L, and 312 (25%) elevated sTFR. The lowest event rates were in iron replete patients with TSAT ≥20% and ferritin ≥100ng/mL (primary outcome=10.1/100 person-years [PY]) - Table. Event rates in iron replete patients with TSAT <20% and ferritin ≥300ng/mL were higher (17.5/100PY) and comparable to guideline-defined ID with TSAT <20% (19.3/100PY). Event rates were intermediary in guideline-defined ID patients with TSAT ≥20% and ferritin <100ng/mL (12.5/100 PY). The risk of the primary composite outcome per log-unit increase was: ferritin=HR 0.88, 95%CI 0.80-0.97; TSAT=0.75, 0.65-0.88; iron=0.79, 0.64-0.97 (and per log-unit decrease in sTFR=0.61, 0.48-0.76).

Conclusion: Low transferrin saturation is a predictor of adverse outcomes in HFrEF, irrespective of ferritin level.
  • Docherty, Kieran  ( University of Glasgow , Glasgow , United Kingdom )
  • Mcmurray, John  ( University of Glasgow , Glasgow , United Kingdom )
  • Brennan, Alice  ( University of Glasgow , Glasgow , United Kingdom )
  • Murugan Sukumar, Shivasankar  ( University of Glasgow , Glasgow , United Kingdom )
  • Welsh, Paul  ( University of Glasgow , Glasgow , United Kingdom )
  • Ponikowski, Piotr  ( Medical University , Wroclaw , Poland )
  • Petrie, Mark  ( University of Glasgow , Glasgow , United Kingdom )
  • Cleland, John  ( University of Glasgow , Glasgow , United Kingdom )
  • Solomon, Scott  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Jhund, Pardeep  ( University of Glasgow , Glasgow , United Kingdom )
    • Author Disclosures:
    Kieran Docherty: DO have relevant financial relationships ; Advisor:Us2.ai:Active (exists now) ; Individual Stocks/Stock Options:Us2.ai:Active (exists now) ; Research Funding (PI or named investigator):Roche:Active (exists now) ; Research Funding (PI or named investigator):Boehringer Ingelheim:Active (exists now) ; Research Funding (PI or named investigator):AstraZeneca:Past (completed) ; Speaker:Boehringer Ingelheim:Past (completed) ; Speaker:Pharmacosmos:Past (completed) ; Speaker:AstraZeneca:Past (completed) | John McMurray: DO have relevant financial relationships ; Research Funding (PI or named investigator):British Heart Foundation, National Institute for Health – National Heart Lung and Blood Institute (NIH-NHLBI), Boehringer Ingelheim, SQ Innovations, Catalyze Group. - Payment to Glasgow University:Active (exists now) ; Other (please indicate in the box next to the company name):KBP Biosciences - My employer, Glasgow University, has been paid by KBP Biosciences for my time spent scientific advisor to company to help guide clinical development in cardio-renal disease, inflammation & infection.:Past (completed) ; Consultant:WIRB-Copernicus Group Clinical Inc. - Data Safety Monitoring Board:Active (exists now) ; Other (please indicate in the box next to the company name):Bayer - My employer, Glasgow University, has been paid by Bayer for my time spent as Steering Committee member for the PANACHE trial using neladenoson bialanate and for the FINEARTS trial with finerenone. These payments were made through a Consultancy with Glasgow University and I have not received personal payments in relation to these trials/drugs.:Active (exists now) ; Other (please indicate in the box next to the company name):Glaxo Smith Kline - My employer, Glasgow University, has been paid by GSK for my time spent as Co-principal investigator and Steering Committee member, respectively, for the Harmony-Outcomes trial (albiglutide) and two trials, ASCEND-D and ASCEND-ND, using daprodustat, and meetings related to these trials. GSK has also paid my travel and accommodation for some of these meetings. These payments were made through a Consultancy with Glasgow University and I have not received personal payments in relation to these trials/drugs.:Active (exists now) ; Other (please indicate in the box next to the company name):Novartis - My employer, Glasgow University, has been paid by Novartis for my time spent as Executive Committee member and then co-principal investigator of ATMOSPHERE, co-principal investigator of the PARADIGM-HF and PARAGON-HF trials and Executive/Steering Committee member for PARADISE-MI, PERSPECTIVE and PARACHUTE-HF trials (with sacubitril/valsartan) and meetings/presentations related to these trials and aliskiren and sacubitril/valsartan. Novartis has also paid my travel and accommodation for some of these meetings. These payments were made through a Consultancy with Glasgow University and I have not received personal payments from Novartis in relation to these trials/drugs.:Active (exists now) ; Other (please indicate in the box next to the company name):Cardurion - My employer, Glasgow University, has been paid by Cardurion for my participation in a company advisory board about development of a PDE 9 inhibitor in heart failure.:Active (exists now) ; Consultant:Global Clinical Trial Partners Ltd. - Director:Active (exists now) ; Consultant:Alynylam Pharmaceuticals, Amgen, AnaCardio, AstraZeneca, Bayer, Berlin Cures, BMS, Cardurion, Cytokinetics, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, River 2 Renal Corp.:Active (exists now) ; Other (please indicate in the box next to the company name):Theracos - My employer, Glasgow University, has been paid by Theracos for my time spent as Principal investigator for the BEST trial and meetings related to this trial. Theracos has also paid my travel and accommodation for some of these meetings. These payments were made through a Consultancy with Glasgow University and I have not received personal payments in relation to this trial/this drug.:Past (completed) ; Other (please indicate in the box next to the company name):Amgen - My employer, Glasgow University, has been paid by Amgen for my time spent as Steering Committee member for the ATOMIC-HF, COSMIC-HF and GALACTIC-HF trials and meetings and other activities related to these trials. Amgen has also paid my travel and accommodation for some of these meetings/activities. These payments were made through a Consultancy with Glasgow University and I have not received personal payments in relation to these trials/this drug.:Active (exists now) ; Other (please indicate in the box next to the company name):Cytokinetics - My employer, Glasgow University, has been paid by Cytokinetics for my time spent as Steering Committee member for the ATOMIC-HF, COSMIC-HF and GALACTIC-HF trials and meetings and other activities related to these trials. Cytokinetics has also paid my travel and accommodation for some of these meetings/activities. These payments were made through a Consultancy with Glasgow University and I have not received personal payments in relation to these trials/this drug.:Active (exists now) ; Speaker:Abbott, Alkem Metabolics, Astra Zeneca, Blue Ocean Scientific Solutions Ltd., Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals Ltd., Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals & Pharmaceuticals Ltd., Lupin Pharmaceuticals, Medscape/Heart.Org., ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, Translational Medicine Academy - personal lecture fees:Active (exists now) ; Other (please indicate in the box next to the company name):AstraZeneca - My employer, Glasgow University, has been paid by AstraZeneca (who market dapagliflozin) for my time spent as Principal Investigator of DAPA-HF and Co-principal Investigator of DELIVER and DETERMINE (trials using dapagliflozin) in heart failure and meetings and other activities related to these trials. AstraZeneca has also paid my travel and accommodation for these meetings. These payments were made through a Consultancy with Glasgow University and I have not received personal payments in relation to this trial/this drug.:Active (exists now) | Alice Brennan: DO NOT have relevant financial relationships | Shivasankar Murugan Sukumar: DO NOT have relevant financial relationships | Paul Welsh: No Answer | Piotr Ponikowski: No Answer | Mark Petrie: DO NOT have relevant financial relationships | John Cleland: DO have relevant financial relationships ; Research Funding (PI or named investigator):Pharmacosmos:Active (exists now) ; Individual Stocks/Stock Options:Viscardia:Active (exists now) ; Individual Stocks/Stock Options:Heartfelt:Active (exists now) ; Research Funding (PI or named investigator):CSL Vifor:Past (completed) | Scott Solomon: DO have relevant financial relationships ; Research Funding (PI or named investigator):Alexion, Alnylam, Applied Therapeutics, AstraZeneca, Bellerophon, Bayer, BMS, Boston Scientific, Cytokinetics, Edgewise, Eidos/BridgeBio, Gossamer, GSK, Ionis, Lilly,NIH/NHLBI, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Tenaya, Theracos, US2.AI:Active (exists now) ; Consultant:Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, BMS, Cardior, Cardurion, Corvia, Cytokinetics, GSK, Intellia, Lilly, Novartis, Roche, Theracos, Quantum Genomics, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, Valo:Active (exists now) | Pardeep Jhund: DO have relevant financial relationships ; Speaker:Novartis:Past (completed) ; Speaker:ProAdwise Communications:Past (completed) ; Research Funding (PI or named investigator):Roche Diagnostics:Active (exists now) ; Research Funding (PI or named investigator):Analog Devices Inc:Active (exists now) ; Research Funding (PI or named investigator):AstraZeneca:Past (completed) ; Speaker:Intas Pharmaceuticals:Past (completed) ; Speaker:Sun Pharmaceuticals:Past (completed) ; Other (please indicate in the box next to the company name):Novo Nordisk - clinical trial work:Active (exists now) ; Other (please indicate in the box next to the company name):Bayer - clinical trial work:Active (exists now) ; Other (please indicate in the box next to the company name):Astrazeneca - clinical trial work:Active (exists now) ; Other (please indicate in the box next to the company name):Novartis - clinical trial work:Past (completed) ; Speaker:AstraZeneca:Past (completed) ; Advisor:Novartis:Past (completed)
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Cracking Comorbidities and Complications in Heart Failure

Sunday, 11/17/2024 , 11:30AM - 12:30PM

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