Early GDMT initiation in suspected HF potentially reduces adverse outcomes

In a retrospective cohort study among patients with suspected HF, elevated NT-proBNP, and a pre-existing non–HF-related treatment indication, early SGLT2 inhibitor and/or MRA therapy was estimated to reduce the risk of HF hospitalization or death ≤12 months.

This summary is based on the publication of Docherty KF, Heywood B, Bayes-Genis A, et al. - Benefit of early initiation of disease-modifying therapy in community-based patients with suspected heart failure. Eur Heart J. 2026 Feb 23;47(8):927-938. doi: 10.1093/eurheartj/ehaf675

Introduction and methods

Background

Patients with suspected HF in the community may frequently experience diagnostic and therapeutic delays [1-4], which could contribute to preventable HF hospitalizations and deaths [4,5]. While SGLT2 inhibitors and MRAs are GDMTs for HF patients, they are also recommended for the treatment of T2D, CKD, or resistant hypertension [6-12]. Initiation of HF therapies at the time elevated NT-proBNP levels are detected in patients with ≥1 of these common comorbidities may reduce the risk of early adverse outcomes while awaiting diagnostic work-up.

Aim of the study

The aim of this study was to estimate the potential effect of early SGLT2 inhibitor and/or MRA initiation on outcomes in patients with suspected HF and a pre-existing non–HF-related indication for this treatment.

Methods

In a retrospective, observational, population-wide cohort study, linked primary care and hospital data of 74,945 patients with no history of HF and no prior prescription of SGLT2 inhibitors or MRAs and who had a community-measured NT-proBNP ≥400 pg/mL in the period January 1, 2015–March 31, 2022, were extracted from the Clinical Practice Research Datalink in the UK. Participants entered the study on the date of the NT-proBNP and were followed up for 12 months.

Patient eligibility for the initiation of SGLT2 inhibitor and/or MRA treatment at the time of the NT-proBNP measurement was assessed based on the documentation of comorbidities and systolic blood pressure and biochemistry values ≤12 months prior. Estimated treatment effects of these GDMTs were extracted from published meta-analyses of large placebo-controlled RCTs in patients with established HF across the LVEF spectrum [13,14].

Outcomes

The primary endpoint was a composite outcome of HF hospitalization as the first recorded HF diagnostic event or all-cause mortality in patients who had no documented HF diagnosis (i.e., no HF hospitalization or outpatient diagnosis) during follow-up and had not undergone echocardiography.

Main results

• Of the 74,945 patients included, 24,082 (32%) were diagnosed with HF ≤12 months of the NT-proBNP measurement, of whom 15,398 (64%) as an outpatient and 8684 (36%) during HF hospitalization.
• In patients with a pre-existing non–HF-related indication for treatment with an SGLT2 inhibitor only (n=24,606; 33%), an estimated 55 (95%CI: 43–67) HF hospitalizations or deaths from any cause at 12 months would be prevented if 1000 patients with no documented HF diagnosis and no echocardiography were treated at the time of detection of NT-proBNP ≥400 pg/mL. This corresponded with a number needed to treat (NNT) of 19 (95%CI: 15–24).
• In those with an MRA indication (n=12,256; 16%), 41 HF hospitalizations or deaths (95%CI: 30–49) per 1000 patients treated could be prevented over 12 months (NNT: 25; 95%CI: 21–33).
• If both an SGLT2 inhibitor and MRA were initiated (n=6372; 9%), an estimated 84 (95%CI: 72–95) adverse events per 1000 patients treated could be avoided over 12 months (NNT: 12 (95%CI: 11–14).
• Among participants with NT-proBNP >2000 pg/mL who were treated with both an SGLT2 inhibitor and MRA, the estimated reduction in adverse events per 1000 patients was 147 (95%CI: 126–166; NNT: 7; 95%CI: 6–8).

Conclusion

This UK retrospective cohort study among community-based patients with suspected HF and a pre-existing non–HF-related indication for treatment (i.e., T2D, CKD, and/or resistant hypertension) estimated that when the treatment with an SGLT2 inhibitor, MRA, or both was initiated at the time an elevated NT-proBNP level is detected, this could reduce the risk of HF hospitalization or all-cause mortality ≤12 months whilst awaiting confirmatory echocardiography. The authors conclude that their “findings suggest a simple clinical strategy with potentially large public health benefits.”

Find this article online at Eur Heart J.

References

1. Bottle A, Kim D, Aylin P, Cowie MR, Majeed A, Hayhoe B. Routes to diagnosis of heart failure: observational study using linked data in England. Heart 2018;104:600–5. https://doi.org/10.1136/heartjnl-2017-312183
2. Hayhoe B, Kim D, Aylin PP, Majeed FA, Cowie MR, Bottle A. Adherence to guidelines in management of symptoms suggestive of heart failure in primary care. Heart 2019;105: 678–85. https://doi.org/10.1136/heartjnl-2018-313971
3. Conrad N, Judge A, Canoy D, Tran J, O’Donnell J, Nazarzadeh M, et al. Diagnostic tests, drug prescriptions, and follow-up patterns after incident heart failure: a cohort study of 93,000 UK patients. PLoS Med 2019;16:e1002805. https://doi.org/10.1371/journal. pmed.1002805
4. Anderson L, Bayes-Genis A, Bodegård J, Mullin K, Gustafsson S, Rosano GMC, et al. Suspected de novo heart failure in outpatient care: the REVOLUTION HF study. Eur Heart J 2025;46:1493–503. https://doi.org/10.1093/eurheartj/ehaf034
5. Morton G, Philip L, Gilpin T, Chan PE, Guha K, Kalra PR. Does specialist review for patients with suspected heart failure predict better outcomes? An observational study on the utility of compliance with NICE guidelines. BMJ Open 2018;8:e021856. https://doi.org/10.1136/bmjopen-2018-021856
6. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599–726. https://doi.org/10.1093/eurheartj/ehab368
7. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2023;44:3627–39. https://doi.org/10.1093/eurheartj/ehad195
8. Kitai T, Kohsaka S, Kato T, Kato E, Sato K, Teramoto K, et al. JCS/JHFS 2025 Guideline on diagnosis and treatment of heart failure. J Card Fail 2025:89:1278–1444. https://doi.org/10.1016/j.cardfail.2025.02.014
9. Chopra V, Khan MS, Abdelhamid M, Abraham WT, Amir O, Anker SD, et al. iCARDIO alliance global implementation guidelines on heart failure 2025. Heart Lung Circ 2025;34: e55–e82. https://doi.org/10.1016/j.hlc.2025.05.094
10. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int 2024;105:S117–314. https://doi.org/10.1016/j.kint.2023.10.018
11. McEvoy JW, McCarthy CP, Bruno RM, Brouwers S, Canavan MD, Ceconi C, et al. 2024 ESC guidelines for the management of elevated blood pressure and hypertension: developed by the task force on the management of elevated blood pressure and hypertension of the European Society of Cardiology (ESC) and endorsed by the European Society of Endocrinology (ESE) and the European Stroke Organisation (ESO). Eur Heart J 2024;45:3912–4018. https://doi.org/10.1093/eurheartj/ehae178
12. Lamprea-Montealegre JA, Madden E, Tummalapalli SL, Chu CD, Peralta CA, Du Y, et al. Prescription patterns of cardiovascular- and kidney-protective therapies among patients with type 2 diabetes and chronic kidney disease. Diabetes Care 2022;45: 2900–6. https://doi.org/10.2337/dc22-0614
13. Vaduganathan M, Docherty KF, Claggett BL, Jhund PS, de Boer RA, Hernandez AF, et al. SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet 2022;400:757–67. https://doi.org/10.1016/S0140-6736(22)01429-5
14. Jhund PS, Talebi A, Henderson AD, Claggett BL, Vaduganathan M, Desai AS, et al. Mineralocorticoid receptor antagonists in heart failure: an individual patient level meta-analysis. Lancet 2024;404:1119–31. https://doi.org/10.1016/S0140-6736(24)01733-1