A new heart failure (HF) treatment effect calculator could help overcome one of the largest barriers to effective heart failure care by predicting the expected effects of treatment on blood pressure, kidney function and potassium levels. The research, presented today at the European Society of Cardiology (ESC) Congress and simultaneously published today in Nature Medicine , uses individual patient data from 38,753 participants across nine major heart failure trials. 1
“Over the last 30 years, we have seen significant treatment advances for patients with heart failure, but adoption of these therapies has been poor,” said Dr Nelson Wang, cardiologist and Senior Research Fellow at The George Institute for Global Health.
“Fear of adverse effects, particularly low blood pressure, worsening kidney function or high potassium levels are the major reasons clinicians do not start treatment,” he said.
The free tool helps address this hurdle by estimating the impact of different treatment combinations on blood pressure (BP), kidney function or estimated glomerular filtration rate (eGFR) and serum potassium levels.
The calculator generates personalised estimates based on patient characteristics, including age, sex, body mass index, baseline blood pressure, kidney function, potassium levels and prior heart failure hospitalisation status.
The tool provides estimates for combinations of five major classes of heart failure therapy: angiotensin receptor blocker – neprilysin inhibitor (ARNI), angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB), sodium glucose cotransporter 2 inhibitor (SGLT2i), steroidal mineralocorticoid receptor antagonist (sMRA) and non-steroidal mineralocorticoid receptor antagonist (nsMRA).
Combination therapy has demonstrated additive benefits in heart failure. Current guidelines recommend a four-pillar treatment approach consisting of a beta-blocker, ARNI, sMRA and SGLT2i for patients with heart failure with reduced ejection fraction which has shown to reduce all-cause mortality by up to 60 per cent. 2 Yet, despite these benefits, registry studies suggest that only 2 per cent of eligible patients receive such treatment. 3
Researchers found that recommended combination therapies were associated with modest reductions in BP and early declines in kidney function, alongside small to modest increases in serum potassium levels. These effects contrasted with substantial reductions in the risk of worsening heart failure events, with risk reductions ranging from 31 to 61 per cent compared with standard care.
The calculator was validated against data from 1,016 participants in four additional trials. Estimated treatment effects were aligned with observed outcomes, supporting the reliability of the model.
Heart failure affects an estimated 64 million people worldwide, with prevalence continuing to rise due to population ageing and improved survival following heart attacks. 4 The condition is associated with high morbidity, reduced quality of life, and a one-year mortality risk of up to 30 per cent. 5 Improving uptake of effective therapies is a key priority in addressing this growing burden of disease.
Dr Wang said the calculator could support clinical decision-making in routine practice.
“By providing a personalised estimate of what to expect when initiating combination therapy, the calculator can reduce uncertainty and give clinicians greater confidence to prescribe these treatments simultaneously, ultimately helping more patients receive therapies that improve long-term outcomes,” he concluded.
This work was a collaboration between The George Institute for Global Health and Brigham and Women’s Hospital, Harvard Medical School. The authors note that the calculator was developed using data from clinical trial populations and that estimates may not be fully generalisable to broader populations. The Heart Failure Treatment Effect Calculator can be accessed at https://hfmodel.org/ .
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References
Nature Medicine
Computational simulation/modeling
People
Short-term effects of Combinations of Heart failure Therapies on Blood Pressure, Kidney Function, and Serum Potassium
31-Aug-2026
N.W. is supported by the Heart Foundation Post-doctoral Fellowship 108288-2024_PDF and Novo Nordisk Cardiometabolic Fellowship. He has received conference support from Bayer, and is involved in the study design of a randomised trial with Edwards LifeSciences. M.V. has received research grant support, served on advisory boards, or had speaker engagements with Alnylam Pharmaceuticals, American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Esperion, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Recordati, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health, and participates on clinical trial committees for studies sponsored by Amgen, AstraZeneca, Boehringer Ingelheim, Galmed, Novartis, Bayer AG, Occlutech, Pharmacosmos, and Impulse Dynamics. M.A.P. reports that he consults for Alexion, AstraZeneca, DalCor Pharmaceuticals, Intellia, and Novo Nordisk; and has equity in DalCor Pharmaceuticals. J.P.F. has received research support from AstraZeneca, Boehringer-Ingelheim, Novartis, Amgen, Salamandra and Bial. F.Z. reports personal fees from 89Bio, Abbott, Acceleron, Applied Therapeutics, Bayer, Betagenon, Boehringer, BMS, CVRx, Cambrian, Cardior, Cereno pharmaceutical, Cellprothera, CEVA, Inventiva, KBP, Merck, Novo Nordisk, Owkin, Otsuka, Roche Diagnostics, Northsea, USa2, having stock options at G3Pharmaceutical and equities at Cereno, Cardiorenal, Eshmoun Clinical research and being the founder of Cardiovascular Clinical Trialists. B.P. declares potential COI in relation to Anacardio, Astra Zeneca, Bayer, Boehringer Ingelheim, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, Lexicon, Prointel, Sarfez Pharmaceuticals, SC Pharmaceuticals, Sea Star Medical, SQ Innovations, Vifor; he has stock options or equities at Anacardio, Cereno Scientific, G3 Pharmaceuticals, KBO Biosciences, Prointel, Safez Pharmaceuticals, SC Pharmaceuticals, Sea Star Medical, SQ Innovations and Vifor. M.P. reports consulting to 89bio, Abbvie, Altimmune, Alnylam, Amarin, Amgen, Ardelyx, AstraZeneca, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Medtronic, Moderna, Novartis, Reata, Relypsa, and Salamandra K.F.D. reports that his employer, the University of Glasgow, has been remunerated by AstraZeneca for his work on clinical trials, and he has received speakers’ fees from AstraZeneca, Boehringer Ingelheim, Pharmacosmos, and Translational Medicine Academy; has served on advisory boards or performed consultancy for Abbott, FIRE-1, Us2.ai, and Bayer AG; has served on a Clinical Endpoint Committee for Bayer AG; and has received research grant support (paid to his institution) from AstraZeneca, Roche Diagnostics, Novartis, and Boehringer Ingelheim. J.J.V.M. has received consulting fees paid to his institution from Alnylam, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardialysis, Cardurion, Dal-Cor, GlaxoSmithKline, Ionis, KBP Biosciences, Merck, Novartis, Pfizer, and Theracos S.D.S. has received grants from Celladon, Eidos, Ionis, Lone Star Heart, Mesoblast, National Institutes of Health/National Heart, Lung, and Blood Institute, and Sanofi Pasteur; has received grants and personal fees from Alnylam, Amgen, AstraZeneca, Bayer, Bellerophon, Bristol Myers Squibb, Cytokinetics, Gilead, GlaxoSmithKline, MyoKardia, Novartis, and Theracos; and has received personal fees from Akros, AoBiome, Arena, Cardiac Dimensions, Cardior, Cardurion, Corvia, Daiichi-Sankyo, Dinaqor, Ironwood, Janssen, Merck, Moderna, Quantum Genomics, Roche, Takeda, and Tenaya. The remaining authors declare no competing interests.