BRIEF REPORT

# Finerenone and Quality of Life Assessed Using the EuroQol 5-Dimension Questionnaire Level-Sum-Score in Patients With Heart Failure and Mildly Reduced or Preserved Ejection Fraction

Mingming Yang, MD, PHD,ᵃ,ᵇ Misato Chimura, MD, PHD,ᵃ,ᶜ Carolyn S.P. Lam, MD, PHD,ᵈ Michele Senni, MD,ᵉ Adriaan A. Voors, MD, PHD,ᵉ Faiez Zannad, MD, PHD,ᵉ Muthiah Vaduganathan, MD, MPH,ᵉ Pardeep S. Jhund, MBCHB, MSc, PHD,ᵃ Scott D. Solomon, MD,ᵇ John J.V. McMurray, MDᵃ

Patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) have significantly impaired health status as measured using disease-specific instruments such as the Kansas City Cardiomyopathy Questionnaire (KCCQ). However, these often older patients frequently have multiple cardiac and noncardiac comorbidities that may have a broader impact on

quality of life not fully captured by disease-specific tools.¹ Thus, there is interest in evaluating more general health-related quality of life (HRQL) in these patients, both to understand the disease condition and the impact of treatment on their overall well-being. The FINEARTS-HF (Study to Evaluate the Efficacy [Effect on Disease] and Safety of Finerenone in Participants With Heart Failure and Left Ventricular Ejection Fraction [Proportion of Blood Expelled Per Heart Stroke] Greater or Equal to 40%; NCT04435626, EudraCT 2020-000306-29) trial showed that the nonsteroidal mineralocorticoid receptor antagonist finerenone significantly reduced the risk of the primary endpoint (total worsening heart failure [HF] events and cardiovascular death): rate ratio: 0.84 [95% CI: 0.74-0.95]; P = 0.007), and improved KCCQ scores in patients with HFmrEF/HFpEF.²,³ However, its effect on generic HRQL has not been evaluated.

**What is the clinical question being addressed?**

Does finerenone improve generic quality of life in patients with HFmrEF/HFpEF?

**What is the main finding?**

Finerenone significantly reduced HF events in HFmrEF/HFpEF across the spectrum of EQ-5D-LSS at baseline. Treatment with finerenone modestly improved generic health status in patients with HFmrEF/HFpEF.

From the ᵇBritish Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom; ᶜDepartment of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; ᵈDepartment of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan; ᵉNational Heart Centre Singapore and Duke-National University of Singapore, Singapore; ᵈUniversity of Milano-Bicocca, Papa Giovanni XXIII Hospital, Bergamo, Italy; ᶠUniversity of Groningen, University Medical Center Groningen, Groningen, Netherlands; ᵇUniversité de Lorraine, Inserm Clinical Investigation Centre, CHU, Nancy, France; and the ᵇCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors' institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

Manuscript received June 17, 2025; revised manuscript received September 8, 2025, accepted September 10, 2025.
ABBREVIATIONS
AND ACRONYMS

**HFmrEF** = heart failure with mildly reduced ejection fraction

**HFpEF** = heart failure with preserved ejection fraction

**HRQL** = health-related quality of life

**KCCQ** = Kansas City Cardiomyopathy Questionnaire

**LSS** = Level-Sum-Score

**nsMRA** = nonsteroidal mineralocorticoid receptor antagonist

**UACR** = urine albumin-to-creatinine ratio

METHODS

The EQ-5D (EuroQol 5-Dimension) questionnaire is a widely used generic HRQL instrument that captures patient-reported health status across 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each rated on 5 levels from “no problem” to “extreme problem” (scoring 1 to 5), enabling a holistic assessment of well-being. One recent approach to analyzing this questionnaire is to calculate the Level-Sum-Score (LSS), which adds the 5 dimension scores equally (range: 5 [best] to 25 [worst]), offering a simple, additive measure of overall health status.⁴ In this prespecified analysis, we calculated the EQ-5D-LSS in FINEARTS-HF participants and evaluated the effect of finerenone vs placebo on this score. The EQ-5D-5L (EuroQol 5-Dimension 5-Level) questionnaire was self-administered at randomization and at 6, 9, and 12 months. Analyses of EQ-5D-LSS were performed under a complete-case approach, consistent with the prespecified statistical analysis plan of FINEARTS-HF. The trial protocol was approved by ethics committees at the 653 participating institutions in 37 countries, and all patients provided written informed consent.

We used baseline EQ-5D-LSS categories as reported in similar prior analysis of other trials: 1) 5; 2) 6-10; 3) 11-15; and 4) 16-25.⁵ All analyses were conducted with Stata version 18 (Stata Corp). A value of *P* < 0.05 was considered statistically significant.

RESULTS

Among the 6,001 patients analyzed, 5,978 (99.6%) had baseline EQ-5D-LSS and 4,852 (80.9%) had 12-month follow-up data. The mean (SD) baseline EQ-5D-LSS was 9.4 (3.6), and the median was 9 (Q1-Q3: 7-12). The distribution of patients across EQ-5D-LSS categories were as follows: score 5, 884 (14.8%); score 6-10, 3,060 (51.2%); score 11-15, 1,621 (27.1%); and score 16-25, 413 (6.9%). Participants with higher (worse) baseline EQ-5D-LSS were more often women, White, obese, and had lower estimated glomerular filtration rate. They also had a higher percentage of several cardiovascular and non-cardiovascular comorbidities (eg, hypertension, atrial fibrillation, stroke, chronic obstructive pulmonary disease, and type 2 diabetes), more frequent prior HF hospitalization, worse KCCQ scores, more advanced NYHA functional class, and higher N-terminal pro-B-type natriuretic peptide and

urine albumin-to-creatinine ratio. These patients were more likely to receive loop diuretics, angiotensin receptor blocker/angiotensin receptor natriuresin inhibitor, and calcium channel blocker.

Patients reporting higher EQ-5D-LSS generally had worse clinical outcomes. The rate of the primary outcome of total (first and recurrent) worsening HF events and cardiovascular death increased across EQ-5D-LSS: 11.5 (95% CI: 9.5-14.0), 14.7 (95% CI: 13.4-16.2), 19.5 (95% CI: 17.4-21.9), and 25.8 (95% CI: 21.1-31.7) per 100 patient-years in score categories 5, 6-10, 11-15, and 16-25, respectively. Similar results were observed with other outcomes, including total worsening HF events (and its components), the composite of time to first worsening HF event or cardiovascular death (and its components) and all-cause death. Covariate-adjusted models showed broadly consistent results.

Compared with placebo, finerenone consistently reduced the risk of the primary outcome across EQ-5D-LSS categories: the rate ratio was 0.87 (95% CI: 0.59-1.29), 0.78 (95% CI: 0.65-0.94), 0.81 (95% CI: 0.65-1.02), and 1.34 (95% CI: 0.88-2.03) for 5, 6-10, 11-15, and 16-25 points respectively (*P*<sub>interaction</sub> = 0.23). Similar patterns were observed for the other outcomes. In addition, finerenone improved KCCQ-Total Symptom Score from baseline to 12 months (mean changes were 1.4, 1.4, 1.9, and 2.3 for score groups 5, 6-10, 11-15, and 16-25, respectively). However, it did not reduce mortality (due to cardiovascular causes or all causes) or improve NYHA functional class.

As we reported previously, the individual domain scores provided additional, possibly surprising, information to that obtained from the KCCQ.⁵ The distributions of scores for the dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) varied markedly by question with 33%/29%/38% reporting no/slight/moderate or greater problem for mobility (“walking about”); 65%/20%/15% for self-care (“washing or dressing myself”); 36%/32%/32% for usual activities (“work, study, housework, family or leisure activities”); 39%/35%/26% for pain/discomfort; and 51%/30%/19% for anxiety/depression.

Treatment with finerenone improved EQ-5D-LSS between baseline and 12 months, with more patients experiencing improvement (finerenone vs placebo, 25.8% vs 24.5%) and fewer had worsening (17.2% vs 18.9%) in EQ-5D-LSS (OR of being in a better category: 1.15 [95% CI: 1.03-1.29]; *P* = 0.013) (Figure 1A). Subgroup analyses showed no treatment heterogeneity by sex (*P*<sub>interaction</sub> = 0.19) or age (<75 vs ≥75 years; *P*<sub>interaction</sub> = 0.20).
<figure><img src="image_1.png" /><figcaption>FIGURE 1 Effect of Finerenone vs Placebo on EQ-5D-LSS and Dimension Scores Over Time (12 Months) in Patients With HFmrEF/HFpEF</figcaption></figure>

Participants randomized to receive finerenone experienced a slightly greater likelihood of improvement in mobility (28.1% vs 26.1%), self-care (16.2% vs 15.9%), usual activities (28.4% vs 27.3%), pain/discomfort (27.5% vs 26.5%), and anxiety/

depression (25.4% vs 24.6%), although only the odds of being in a better category in mobility was statistically significant (Figure 1B). Fewer patients on finerenone experienced worsening in pain/discomfort and anxiety/depression by 12 months (Figure 1B).
Safety outcomes were largely consistent across EQ-5D-LSS categories. Finerenone was associated with more hyperkalemia and creatinine increases, and less hypokalemia, with no heterogeneity by EQ-5D-LSS. However, hypotension (systolic blood pressure <100 mm Hg) occurred more frequently in patients with lower EQ-5D-LSS.

## DISCUSSION

Before FINEARTS-HF, there were no data on the impact of finerenone on generic health status in HFmrEF/HFpEF. The only other study we know of that evaluated EQ-5D-LSS examined dapagliflozin in the combined DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With PReserved Ejection Fraction Heart Failure) trials, and showed improvement in several individual domains.⁵

## CONCLUSIONS

Finerenone, when added to usual therapy, significantly reduced HF events in patients with HFmrEF/HFpEF across the spectrum of baseline EQ-5D-LSS. Treatment with finerenone had a modest but consistent effect on overall patient well-being.

## FUNDING SUPPORT AND AUTHOR DISCLOSURES

Drs McMurray and Jhund are supported by British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217 and the Vera Melrose Heart Failure Research Fund. The FINEARTS-HF trial was funded by Bayer. Dr Yang has received Global CardioVascular Clinical Trialists (CVCT) Young Trialist Grant and travel grants from AstraZeneca and Bayer. Dr Chimura has received grants from the Daiwa Foundation and the Japan Research Foundation for Clinical Pharmacology during the conduct of the study; and personal fees from Otsuka Pharma outside the submitted work. Dr Lam has received research support from Novo Nordisk and Roche Diagnostics; consulting fees from Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Bioeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, CPC Clinical Research, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research and Development LLC, Medscape/ WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and is a co-founder and nonexecutive director of Us2.ai. Dr Senni has served on advisory boards for, served as a consultant for, and received honoraria from Novartis, Abbott, Merck, Merck Sharp and Dohme, Vifor, AstraZeneca, Cardurion, Novo Nordisk, Bayer, and Boehringer Ingelheim. Dr Voors' employer has received consultancy fees and/or research support from Adrenomed, Anacardio, AstraZeneca, Bayer AG, Bristol Myers Squibb, Boehringer Ingelheim, Corteria, EliLilly, Merck, Moderna, Novartis, Novo Nordisk, Roche Diagnostics, and SalubrisBio. Dr Zannad has received personal fees from 89Bio, Abbott,

Acceleron, Applied Therapeutics, Bayer, Betagenon, Boehringer, BMS, CVRx, Cambrian, Cardior, Cereno Pharmaceutical, Cellprothera, CEVA, Inventiva, KBP, Merck, Novo Nordisk, Owin, Otsuka, Roche Diagnostics, Northsea, and USA2; has stock options at G3Pharmaceutical and equities at Cereno, Cardiorenal, and Eshmoun Clinical Research; and is the founder of Cardiovascular Clinical Trialists. Dr Vaduganathan has 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, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and participates on clinical trial committees for studies sponsored by Amgen, AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. Dr Jhund has received speaker fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, Sun Pharmaceuticals, and Intas Pharmaceuticals; has received advisory board fees from AstraZeneca, Boehringer Ingelheim, and Novartis; has received research funding from AstraZeneca, Boehringer Ingelheim, Analog Devices Inc; his employer, the University of Glasgow, has been remunerated for clinical trial work from AstraZeneca, Bayer AG, Novartis, and Novo Nordisk; and is the director of Global Clinical Trial Partners (GCTP). Dr Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and S2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellPro-Thera, Moderna, American Regent, and Sarepta. Dr McMurray's institution, Glasgow University, has received payments for clinical trials and other research projects from the British Heart Foundation, National Institutes of Health-National Heart, Lung, and Blood Institute, Alynylam Pharmaceuticals, AstraZeneca, Bayer, Cardurion, Cytokinetics, Novartis, and Roche. Dr McMurray has received personal consultancy fees from Alynylam Pharmaceuticals, AnaCardio, AstraZeneca, Bayer, Cardurion, Cytokinetics, Novartis, River BioMedics, Biohaven Pharmaceuticals, Chugai Pharmaceuticals, Protherics Medicine Developments Ltd, and DalCor Pharmaceuticals; personal lecture fees from Alkem Metabolics, AstraZeneca, Canadian Medical and Surgical Knowledge, Centrix Healthcare, Emcure Pharmaceuticals, Eris Lifesciences, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals and Pharmaceuticals, Lupin Pharmaceuticals, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, Translational Medicine Academy, Regeneron, MCI India, Hilton Pharmaceuticals, IMEDIC Pharmaceuticals Micro Labs Ltd, At the Limits Ltd, and ARMGO Pharmaceuticals; and has served on data safety monitoring boards for WCG Clinical Services. He is a director of Global Clinical Trial Partners Ltd (which provides clinical trial services such as endpoint committees and educational programs).

ADDRESS FOR CORRESPONDENCE: Prof John J.V. McMurray, British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, United Kingdom. E-mail: john.mcmurray@glasgow.ac.uk.
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**KEY WORDS** ejection fraction, EuroQol 5-Dimension 5-Level questionnaire, finerenone, heart failure, nonsteroidal mineralocorticoid receptor antagonist