Scientific Sessions 2024  /  Frontiers in HFpEF Part 2: On-Treatment Effects, Predictors, and More!  /  Systolic Blood Pressure in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: A Pooled Participant-Level Analysis of 4 Large-Scale Trials
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American Heart Association

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Final ID: Mo2187

Systolic Blood Pressure in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: A Pooled Participant-Level Analysis of 4 Large-Scale Trials

Abstract Body (Do not enter title and authors here): Background
Hypertension is common in patients with heart failure with preserved ejection fraction (HFpEF). Treatment of systolic blood pressure (SBP) to a target <130 mmHg in this population is often recommended based on general ACC/AHA and ESC hypertension guidelines but limited data are available to substantiate this recommendation in patients with HF. We aimed to explore the impact of baseline SBP on cardiovascular (CV) outcomes in a pooled dataset of 4 large, well-characterized cohorts of patients with HF with mildly reduced EF (mrEF) or HFpEF.

Methods
I-PRESERVE, TOPCAT, PARAGON-HF and DELIVER were global, multicenter, randomized clinical trials testing irbesartan, spironolactone, sacubitril/valsartan and dapagliflozin respectively, against either a placebo or an active control (valsartan, in PARAGON-HF), in patients with HF and a LVEF >40% (in DELIVER) or ≥45% (in all other 3 trials). The continuous relationship between baseline SBP and the incidence rates (IR) of 1st HF hospitalization (HFH) or CV death was analyzed with restricted cubic splines and adjusted for known risk factors of CV disease.

Results
A total of 18,627 patients (mean age 71±9 years, 49% men, mean SBP 131±15 mmHg) were included. Over a median follow-up of 2.9 years, 3,852 patients experienced a first HFH or CV death (7.4 events per 100py). The relationship between the IR of 1st HFH or CV death and SBP appeared to be nonlinear, J-shaped (Figure 1), with a nadir of IR observed for SBP values between 120 and 130 mmHg, and an increase for SBP values above 130 mmHg. Above 130 mmHg, each 5 mmHg-increase in SBP was associated with a significantly higher risk of the primary outcome (adjusted HR: 1.07; 95% CI: 1.05-1.10). When stratifying the study population by sex, men had a higher risk for 1st HFH or CV death across the spectrum of SBP. The J-shaped relationship remained consistent in both men and women (Pinteraction=0.43; Figure 2).

Conclusions
Our analysis of a large pooled dataset from 4 clinical trials including over 18,600 patients with HFmrEF or pEF suggests a graded relationship between SBP and CV risk, with risk nadir at SBP between 120 to 130 mmHg, without evidence of difference according to sex.
  • Lu, Henri  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Kondo, Toru  ( Nagoya University , Nagoya , Japan )
  • Claggett, Brian  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Vaduganathan, Muthiah  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Neuen, Brendon  ( George Institute for Global Health , Newtown , New South Wales , Australia )
  • Beldhuis, Iris  ( UMCG , Groningen , Netherlands )
  • Jhund, Pardeep  ( BHF CARDIOVASCULAR RESEARCH CENTRE , Glasgow , United Kingdom )
  • Mc Causland, Finnian  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Anand, Inder  ( VA SAN DIEGO HEATHCARE SYSTEM , La Jolla , California , United States )
  • Pfeffer, Marc  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Pitt, Bertram  ( University of Michigan School , Ann Arbor , Michigan , United States )
  • Zannad, Faiez  ( INSERM-CIC , Vandoeuvre Les Nancy , France )
  • Zile, Michael  ( MEDICAL UNIV OF SOUTH CAROLINA , Charleston , South Carolina , United States )
  • Mcmurray, John  ( BHF CARDIOVASCULAR RESEARCH CENTRE , Glasgow , United Kingdom )
  • Solomon, Scott  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Desai, Akshay  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
    • Author Disclosures:
    Henri Lu: DO have relevant financial relationships ; Other (please indicate in the box next to the company name):Gottfried und Julia Bangerter-Rhyner Foundation (fellowship funding):Active (exists now) ; Other (please indicate in the box next to the company name):Société Académique Vaudoise (fellowship funding):Active (exists now) ; Other (please indicate in the box next to the company name):SICPA Foundation (fellowship funding):Active (exists now) | Marc Pfeffer: DO have relevant financial relationships ; Consultant:Alexion, Alnylam, Apnimed, AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, DalCor, Intellia, Novartis, and Novo Nordisk. :Active (exists now) ; Individual Stocks/Stock Options:Dal-Cor:Active (exists now) ; Researcher:Lexicon, Novartis:Past (completed) | Bertram Pitt: No Answer | Faiez Zannad: No Answer | Michael Zile: DO NOT have relevant financial relationships | 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) | 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) | Akshay Desai: DO have relevant financial relationships ; Research Funding (PI or named investigator):Abbott:Active (exists now) ; Individual Stocks/Stock Options:DTX plus:Past (completed) ; Consultant:Veristat, Zydus:Past (completed) ; Consultant:Medpace, Porter Health, Regeneron, River2Renal, Roche, Verily:Active (exists now) ; Consultant:Merck, Medtronic, Parexel, scPharmaceuticals:Past (completed) ; Consultant:Bayer, Biofourmis, Novartis:Active (exists now) ; Consultant:Avidity, Axon Therapeutics, Boston Scientific, GlaxoSmithKline:Past (completed) ; Consultant:Abbott, Alnylam, AstraZeneca:Active (exists now) ; Research Funding (PI or named investigator):Pfizer:Active (exists now) ; Research Funding (PI or named investigator):Novartis:Active (exists now) ; Research Funding (PI or named investigator):Bayer:Active (exists now) ; Research Funding (PI or named investigator):AstraZeneca:Active (exists now) ; Research Funding (PI or named investigator):Alnylam:Active (exists now) | Toru Kondo: DO have relevant financial relationships ; Advisor:Astrazeneca:Active (exists now) ; Speaker:Novartis Pharma K.K:Active (exists now) ; Speaker:Kyowa Kirin Co.,Ltd.:Active (exists now) ; Speaker:Kowa Company, Ltd:Active (exists now) ; Speaker:Ono Pharmaceutical Co., Ltd:Active (exists now) ; Speaker:Boehringer Ingelheim:Active (exists now) ; Speaker:Abbott Japan LLC:Active (exists now) | Brian Claggett: DO have relevant financial relationships ; Consultant:Cardior:Active (exists now) ; Consultant:Eli Lilly:Active (exists now) ; Consultant:CVRx:Past (completed) ; Consultant:Intellia:Active (exists now) ; Consultant:Cytokinetics:Past (completed) ; Consultant:Cardurion:Active (exists now) | Muthiah Vaduganathan: DO have relevant financial relationships ; Researcher:received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health, and participates on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics:Active (exists now) | Brendon Neuen: DO have relevant financial relationships ; Consultant:AstraZeneca:Active (exists now) ; Research Funding (PI or named investigator):Menarini:Expected (by end of conference) ; Consultant:Travere Therapeutics:Active (exists now) ; Consultant:Novo Nordisk:Active (exists now) ; Consultant:Boehringer and Ingelheim:Active (exists now) ; Consultant:Bayer:Active (exists now) ; Consultant:Alexion:Active (exists now) | Iris Beldhuis: DO have relevant financial relationships ; Research Funding (PI or named investigator):Dutch Heart Foundation:Active (exists now) ; Research Funding (PI or named investigator):Novartis:Active (exists now) | Pardeep Jhund: DO have relevant financial relationships ; Consultant:AstraZeneca:Active (exists now) ; Other (please indicate in the box next to the company name):Director GCTP :Active (exists now) ; Researcher:Analog Devices :Active (exists now) ; Researcher:Roche Diagnostics:Active (exists now) ; Researcher:AstraZeneca:Past (completed) ; Researcher:Boheringer Ingelheim:Past (completed) ; Consultant:Bayer:Active (exists now) | Finnian Mc Causland: DO have relevant financial relationships ; Research Funding (PI or named investigator):Lexicon:Active (exists now) ; Other (please indicate in the box next to the company name):Rubin-Anders Scientific (expert witness):Active (exists now) ; Consultant:Zydus:Active (exists now) ; Consultant:GSK:Active (exists now) ; Research Funding (PI or named investigator):NIDDK:Active (exists now) ; Research Funding (PI or named investigator):Novartis:Active (exists now) | Inder Anand: DO NOT have relevant financial relationships
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Frontiers in HFpEF Part 2: On-Treatment Effects, Predictors, and More!

Monday, 11/18/2024 , 01:30PM - 02:30PM

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