# Efficacy and Safety of the Kidney Function-Based Finerenone Dosing Strategy Used in FINEARTS-HF

Misato Chimura, Alasdair D Henderson, Pardeep S Jhund, Brian L Claggett, Akshay S Desai, Gerasimos Filippatos, Grzegorz Gajos, Meike Brinker, Flaviana Amarante, James Lay-Flurrie, et al.

► To cite this version:

Misato Chimura, Alasdair D Henderson, Pardeep S Jhund, Brian L Claggett, Akshay S Desai, et al. Efficacy and Safety of the Kidney Function-Based Finerenone Dosing Strategy Used in FINEARTS-HF. JACC: Heart Failure, 2026, pp.102938. 10.1016/j.jchf.2026.102938. hal-05500029

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ORIGINAL RESEARCH

# Efficacy and Safety of the Kidney Function-Based Finerenone Dosing Strategy Used in FINEARTS-HF

Misato Chimura, MD, PHD,ª,ᵇ Alasdair D. Henderson, PHD,ª Pardeep S. Jhund, MBCHB, MSc, PHD,ª

Brian L. Claggett, PHD,ᶜ Akshay S. Desai, MD, MPH,ᶜ Gerasimos Filippatos, MD,ᵈ Grzegorz Gajos, MD, PHD,ᵉ

Meike Brinker, MD,>f Flaviana Amarante, MD,> James Lay-Flurrie, MSc,> Katja Rohwedder, MD,>

Carolyn S.P. Lam, MD, PHD, g Naoki Sato, MD, PHD, h Michele Senni, MD, i Adriaan A. Voors, MD, j Faiez Zannad, MD, k

Mehmet B. Yilmaz, MD, l Bertram Pitt, MD, m Muthiah Vaduganathan, MD, MPH, c Scott D. Solomon, MD, c

John J.V. McMurray, MDª

## ABSTRACT

**BACKGROUND** Given that mineralocorticoid receptor antagonists have the potential to impair renal function and induce hyperkalemia, close monitoring of estimated glomerular filtration rate (eGFR) and serum potassium levels is essential to ensure the safe administration of this therapy.

**OBJECTIVES** In this prespecified analysis, the authors evaluated the efficacy and safety of the kidney function-based finerenone dosing strategy used in the FINEARTS-HF trial.

**METHODS** In FINEARTS-HF, patients with an eGFR of 25 to 60 mL/min/1.73 m² at baseline were stratified at randomization to the low-dose group and started on 10 mg of finerenone once daily (titrated to a maximum 20 mg/d) or matching placebo, whereas those with an eGFR >60 mL/min/1.73 m² at baseline were stratified to the high-dose group and started on 20 mg of finerenone once daily (titrated to a maximum 40 mg/d) or matching placebo. The primary outcome was the composite of total (first and recurrent) heart failure events and cardiovascular death.

**RESULTS** Among 5,986 (99.8%) analyzable patients, 3,159 were assigned to the higher eGFR/high-dose stratum and 2,827 to the lower eGFR/low-dose stratum group. The mean ± SD achieved dose was 32.3 ± 9.1 mg (finerenone) and 34.4 ± 7.8 mg (placebo) in the higher eGFR/high-dose stratum, and 15.6 ± 4.3 mg (finerenone) and 16.7 ± 4.0 mg (placebo) in the lower eGFR/low-dose stratum. The effect of finerenone on the primary outcome was consistent across the 2 dosing strata (higher eGFR/high-dose stratum: rate ratio: 0.77 [95% CI: 0.63-0.94] vs lower eGFR/low-dose stratum: rate ratio: 0.87 [95% CI: 0.74-1.03]; *P* for interaction = 0.34). Consistent benefits were observed for the components of the primary outcome and all-cause death. Safety was also consistent between dosing strata, except for hypokalemia, where the reduction in the odds of hypokalemia with finerenone compared to placebo was greater in the higher eGFR/high-dose stratum (*P*-interaction < 0.01).

**CONCLUSIONS** In FINEARTS-HF, an eGFR-based dosing strategy allowed effective and safe use of finerenone in patients with heart failure with mildly reduced ejection fraction/ heart failure with preserved ejection fraction with a baseline eGFR as low as 25 mL/min/1.73 m². We recommend that clinicians implement the trial-validated dosing strategy and incorporate appropriate uptration to the target dose to ensure optimal therapeutic outcomes. (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) (JACC Heart Fail. 2026;■:102938) © 2026 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
ABBREVIATIONS
AND ACRONYMS

eGFR = estimated glomerular filtration rate

HF = heart failure

LVEF = left ventricular ejection fraction

MRA = mineralocorticoid receptor antagonist

NT-proBNP = N-terminal pro-B-type natriuretic peptide

Because mineralocorticoid receptor antagonists (MRAs) can cause worsening of kidney function and hyperkalemia, careful monitoring of estimated glomerular filtration rate (eGFR) and plasma potassium is key to the safe use of this type of therapy.<sup>1-10</sup> As these adverse effects of MRAs are dose-dependent, dose-adjustment plays a key role in minimizing risk.<sup>11</sup> Although there was no prospective stratification of the initial dose of spironolac-
tone in RALES (Randomized Aldactone Evaluation Study), in EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure), eplerenone (or matching placebo) was started at a dose of 25 mg once daily, or 25 mg on alternate days, depending on baseline eGFR (ie, ≥50 mL/min/1.73 m<sup>2</sup> vs 30 to 49 mL/min/1.73 m<sup>2</sup>, respectively).<sup>1-3</sup> Potassium and eGFR permitting, the dose could be increased to 50 mg once daily or 25 mg once daily (or matching placebo) in the respective eGFR strata. A similar strategy was adopted with the new nonsteroidal MRA finerenone in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) enrolled in 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)<sup>12,13</sup> trial. In FINEARTS-HF, participants with an eGFR of 25 to 60 mL/min/1.73 m<sup>2</sup> were assigned to once-daily dosing with 10 mg finerenone (or matching placebo) increasing to 20 mg and those with an eGFR >60 mL/min/1.73 m<sup>2</sup> were assigned to finerenone 20 mg once daily (or matching placebo) increasing to 40 mg. In this prespecified analysis, we report the efficacy and safety of finerenone

compared to placebo within these eGFR-based dose strata.

METHODS

FINEARTS-HF TRIAL DESIGN AND OBJECTIVES.

The design and results of FINEARTS-HF are published.<sup>12-14</sup> Key inclusion criteria were age ≥40 years, symptomatic heart failure (HF) in NYHA functional class II-IV, and left ventricular ejection fraction (LVEF) ≥40%. Patients were also required to have elevated concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Key exclusion criteria were eGFR <25 mL/min/1.73 m<sup>2</sup>, serum potassium >5.0 mmol/L, and the history of hyperkalemia or acute renal failure during MRA treatment for >7 consecutive days leading to permanent discontinuation of the MRA treatment. Ethics committees for the 653 participating institutions in 37 countries approved the protocol, and all patients gave written consent.

DOSE TITRATION AND MONITORING OF SAFETY AND TOLERABILITY. The study protocol encouraged achieving and maintaining the maximum tolerated maintenance dose of the study drug. Serial measurements of serum potassium and creatinine were conducted at scheduled study visits to monitor prespecified safety events, including hyperkalemia and worsening renal function. Participants were stratified according to baseline eGFR and randomly assigned in a 1:1 ratio to receive either finerenone or matching placebo. Those with a baseline eGFR of 25 to 60 mL/min/1.73 m<sup>2</sup> were stratified to the low-dose group and initiated treatment at 10 mg once daily (maximum of 20 mg/d), whereas those with a baseline eGFR >60 mL/min/1.73 m<sup>2</sup> were stratified to the high-dose group and started at 20 mg once daily (maximum of 40 mg/d). Dose up titration was permitted any time from week 4 onwards,

From the <sup>a</sup>British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom;
<sup>b</sup>Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan; <sup>c</sup>Cardiovascular Division,
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; <sup>d</sup>National and Kapodistrian University of
Athens, School of Medicine, Attikon University Hospital, Department of Cardiology, Athens, Greece; <sup>e</sup>Department of Coronary
Disease and Heart Failure, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; <sup>f</sup>Bayer AG, Berlin,
Germany; <sup>g</sup>National Heart Centre Singapore and Duke-National University of Singapore, Singapore; <sup>h</sup>Kawaguchi Cardiovascular
and Respiratory Hospital, Saitama, Japan; <sup>i</sup>University of Milano-Bicocca, Papa Giovanni XXIII Hospital, Bergamo, Italy; <sup>j</sup>Uni-
versity Medical Center Groningen, Groningen, the Netherlands; <sup>k</sup>Université de Lorraine, Inserm Clinical Investigation Centre,
CHU, Nancy, France; <sup>l</sup>Department of Cardiology, Faculty of Medicine, Dokuz Eylül University, Izmir, Türkiye; and the <sup>m</sup>Uni-
versity of Michigan, School of Medicine, Ann Arbor, Michigan, USA.

Biykem Bozkurt, MD, PhD, served as acting Editor-in-Chief and main adjudicator for this paper.

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.
provided that serum potassium levels remained within an acceptable range and eGFR had not declined by ≥30% compared to the previous scheduled visit. Dose downtitration was advised at any time if serum potassium reached ≥5.5 mmol/L, and treatment could be temporarily interrupted if the patient was already receiving the lowest dose. If serum potassium was ≥6.0 mmol/L, temporary discontinuation of the study drug and repeat testing of potassium levels within 72 hours were recommended. Detailed recommendations for the dosage and administration of the study intervention are provided in the design paper.¹²

**TRIAL OUTCOMES.** The primary outcome was the composite of total (first and recurrent) HF events (including unplanned HF hospitalizations or urgent HF events) and cardiovascular death. The secondary outcomes included total HF events; cardiovascular death; change from baseline to 6, 9, and 12 months in the Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS); improvement in NYHA functional class from baseline to 12 months; and all-cause death. The prespecified safety outcomes included the incidence of hyperkalemia (defined as serum potassium >5.5 mmol/L or >6.0 mmol/L), hypokalemia (defined as serum potassium <3.5 mmol/L or <4.0 mmol/L), elevation of serum creatinine (defined as serum creatinine ≥2.5 mg/dL or ≥3.0 mg/dL), and hypotension (defined as systolic blood pressure <100 mm Hg).

**STATISTICAL ANALYSIS.** Baseline characteristics were summarized as frequencies with percentages, mean ± SD, or median (Q1-Q3). Differences in baseline characteristics were assessed using the chi-square test for binary or categorical variables, and the Wilcoxon test and 2-sample Student's t-test for non-normal and normal continuous variables, respectively. To compare the effects of finerenone vs placebo on clinical outcomes according to dose groups, time-to-event data and total events were evaluated with Cox proportional-hazards models and semiparametric proportional-rates models,¹⁵ respectively, and these models were stratified according to geographic region and LVEF stratification. The proportional hazards assumption was tested by using the Schoenfeld residuals, and the assumption was met. As a sensitivity analysis, a competing risk analysis accounting for the competing risk of all-cause death (for time to first HF event), and noncardiovascular death (for the outcomes of cardiovascular death and the composite of cardiovascular death or first HF event) was conducted in a Fine-Gray subdistribution hazards model. The proportion of patients with

improvement in NYHA functional class from baseline to 12 months was analyzed using a logistic regression model, adjusted for geographic region and LVEF stratification, and odds ratios (ORs) were reported. Change in KCCQ-TSS from baseline to 12 months was analyzed using linear regression adjusted for baseline KCCQ-TSS, geographic region, and baseline LVEF (<60% or ≥60%) strata. Incidences of the safety endpoints were estimated using logistic regression models adjusted for stratification factors for the variables above, with interaction by eGFR/dose strata tested via a likelihood ratio test. Changes in the finerenone or placebo dose, eGFR, NT-proBNP [log], potassium, and the urine albumin/creatinine ratio (UACR) were analyzed using mixed-effects models for repeated measures that were adjusted for baseline values, follow-up visits (categorical indicator), treatment, the visit-by-treatment interaction, the eGFR strata-by-treatment interaction and stratification factors with a random intercept for each patient, and assumed that the random effects variance-covariance matrix was unstructured. We did not impute missing values from the analysis, and missing values were assumed to be missing at random. The assumption of normality, homogeneity of variance of residuals, and linearity of continuous predictors were fulfilled.

In an ancillary analysis, we also examined changes in potassium in RALES according to baseline eGFR (<60 mL/min/1.73 m² vs ≥60 mL/min/1.73 m²) using mixed-effects models for repeated measures that were adjusted for baseline values, follow-up visits (categorical indicator), treatment, the baseline eGFR group-by-treatment interaction, and the visit-by-treatment interaction with a random intercept for each patient, and assumed that the random effects variance-covariance matrix was unstructured. The purpose of this analysis was to look at change in potassium in the same eGFR strata in a trial where MRA dosing was not modified according to kidney function. All estimates and 95% CIs were calculated based on model-estimated SEs.

All statistical analyses were conducted with STATA version 18 (StataCorp LLC), and value of P < 0.05 was considered nominally significant.

## RESULTS

**BASELINE CHARACTERISTICS ACCORDING TO eGFR/DOSE STRATUM.** Among 5,986 analyzable patients (99.8%), a total of 3,159 patients were stratified to the higher eGFR/high-dose stratum (finerenone: 1,575; placebo: 1,584), and 2,827 patients were stratified to the lower eGFR/low-dose stratum
<table><caption>TABLE 1 Baseline Characteristics According to eGFR/Dose Stratum</caption><thead><tr><th rowspan="2"></th><th colspan="2">Higher eGFR/High-Dose Stratum</th><th colspan="2">Lower eGFR/Low-Dose Stratum</th></tr><tr><th>Finerenone (n = 1,575)</th><th>Placebo (n = 1,584)</th><th>Finerenone (n = 1,418)</th><th>Placebo (n = 1,409)</th></tr></thead><tbody><tr><td>Age, y</td><td>69.1 ± 9.7</td><td>68.8 ± 9.6</td><td>75.1 ± 8.4</td><td>75.7 ± 8.4</td></tr><tr><td>Male</td><td>932 (59.2)</td><td>937 (59.2)</td><td>711 (50.1)</td><td>682 (48.4)</td></tr><tr><td>Region</td><td></td><td></td><td></td><td></td></tr><tr><td>Asia</td><td>271 (17.2)</td><td>265 (16.7)</td><td>221 (15.6)</td><td>223 (15.8)</td></tr><tr><td>Eastern Europe</td><td>759 (48.2)</td><td>802 (50.6)</td><td>568 (40.1)</td><td>517 (36.7)</td></tr><tr><td>Latin America</td><td>174 (11.0)</td><td>167 (10.5)</td><td>148 (10.4)</td><td>152 (10.8)</td></tr><tr><td>North America</td><td>101 (6.4)</td><td>92 (5.8)</td><td>133 (9.4)</td><td>144 (10.2)</td></tr><tr><td>Western Europe, Oceania, other</td><td>270 (17.1)</td><td>258 (16.3)</td><td>348 (24.5)</td><td>373 (26.5)</td></tr><tr><td>Race</td><td></td><td></td><td></td><td></td></tr><tr><td>Asian</td><td>273 (17.3)</td><td>270 (17.0)</td><td>223 (15.7)</td><td>227 (16.1)</td></tr><tr><td>Black</td><td>26 (1.7)</td><td>17 (1.1)</td><td>23 (1.6)</td><td>22 (1.6)</td></tr><tr><td>White</td><td>1,226 (77.8)</td><td>1,251 (79.0)</td><td>1,131 (79.8)</td><td>1,115 (79.1)</td></tr><tr><td>Other</td><td>50 (3.2)</td><td>46 (2.9)</td><td>41 (2.9)</td><td>45 (3.2)</td></tr><tr><td>HF characteristics</td><td></td><td></td><td></td><td></td></tr><tr><td>NYHA functional class</td><td></td><td></td><td></td><td></td></tr><tr><td>II</td><td>1,152 (73.2)</td><td>1,148 (72.5)</td><td>922 (65.0)</td><td>913 (64.8)</td></tr><tr><td>III</td><td>415 (26.4)</td><td>424 (26.8)</td><td>485 (34.2)</td><td>486 (34.5)</td></tr><tr><td>IV</td><td>7 (0.4)</td><td>12 (0.8)</td><td>11 (0.8)</td><td>10 (0.7)</td></tr><tr><td>Any prior hospitalization for HF</td><td>923 (58.6)</td><td>923 (58.3)</td><td>867 (61.1)</td><td>894 (63.4)</td></tr><tr><td>LVEF, %</td><td>52.1 ± 7.7</td><td>51.8 ± 7.7</td><td>53.2 ± 7.9</td><td>53.3 ± 7.9</td></tr><tr><td>KCCQ-TSS</td><td>69.2 ± 23.5</td><td>68.5 ± 23.3</td><td>65.7 ± 24.3</td><td>64.2 ± 24.4</td></tr><tr><td>Physiological and laboratory measurements</td><td></td><td></td><td></td><td></td></tr><tr><td>Systolic blood pressure, mm Hg</td><td>129.5 ± 14.9</td><td>129.6 ± 14.8</td><td>129.5 ± 15.8</td><td>129.0 ± 15.9</td></tr><tr><td>Diastolic blood pressure, mm Hg</td><td>76.7 ± 9.7</td><td>76.7 ± 10.0</td><td>74.3 ± 10.7</td><td>73.8 ± 10.6</td></tr><tr><td>Heart rate, beats/min</td><td>71.7 ± 11.4</td><td>71.2 ± 11.6</td><td>71.6 ± 12.1</td><td>71.2 ± 12.2</td></tr><tr><td>BMI, kg/m²</td><td>29.7 ± 6.0</td><td>30.2 ± 6.2</td><td>30.0 ± 6.2</td><td>29.8 ± 6.1</td></tr><tr><td>BMI groups, kg/m²</td><td></td><td></td><td></td><td></td></tr><tr><td>&lt;18.5 (underweight)</td><td>21 (1.3)</td><td>12 (0.8)</td><td>12 (0.8)</td><td>20 (1.4)</td></tr><tr><td>18.5 to &lt;25 (normal weight)</td><td>343 (21.8)</td><td>326 (20.6)</td><td>285 (20.2)</td><td>285 (20.3)</td></tr><tr><td>25 to &lt;30 (overweight)</td><td>519 (33.0)</td><td>519 (32.8)</td><td>473 (33.5)</td><td>472 (33.6)</td></tr><tr><td>30 to &lt;35 (class I obesity)</td><td>405 (25.7)</td><td>415 (26.2)</td><td>359 (25.4)</td><td>363 (25.8)</td></tr><tr><td>≥35 (class II-III obesity)</td><td>285 (18.1)</td><td>309 (19.5)</td><td>284 (20.1)</td><td>266 (18.9)</td></tr><tr><td>NT-proBNP, pg/mL</td><td>869 (377-1,558)</td><td>808 (356-1,560)</td><td>1,336 (593-2,328)</td><td>1,331 (593-2,584)</td></tr><tr><td>eGFR, mL/min/1.73 m²</td><td>74.3 (65.4-85.6)</td><td>76.1 (66.2-86.4)</td><td>46.4 (38.1-53.8)</td><td>45.8 (37.3-53.3)</td></tr><tr><td>UACR, mg/g</td><td>103.3 ± 498.4</td><td>102.8 ± 378.0</td><td>225.6 ± 719.5</td><td>229.1 ± 785.5</td></tr><tr><td>Potassium, mmol/L</td><td>4.4 ± 0.4</td><td>4.3 ± 0.4</td><td>4.4 ± 0.5</td><td>4.4 ± 0.5</td></tr><tr><td>HbA1c, %</td><td>6.4 ± 1.2</td><td>6.3 ± 1.1</td><td>6.5 ± 1.2</td><td>6.5 ± 1.2</td></tr><tr><td>Medical history</td><td></td><td></td><td></td><td></td></tr><tr><td>Hypertension</td><td>1,338 (85.0)</td><td>1,393 (87.9)</td><td>1,293 (91.2)</td><td>1,288 (91.4)</td></tr><tr><td>Diabetes mellitus</td><td>576 (36.7)</td><td>585 (37.0)</td><td>636 (45.0)</td><td>636 (45.3)</td></tr><tr><td>Myocardial infarction</td><td>449 (28.5)</td><td>420 (26.5)</td><td>335 (23.6)</td><td>337 (23.9)</td></tr><tr><td>Coronary artery bypass graft</td><td>234 (14.9)</td><td>242 (15.3)</td><td>226 (15.9)</td><td>214 (15.2)</td></tr><tr><td>Percutaneous coronary intervention</td><td>407 (25.8)</td><td>386 (24.4)</td><td>337 (23.8)</td><td>339 (24.1)</td></tr><tr><td>AF (history)</td><td>780 (49.5)</td><td>781 (49.3)</td><td>860 (60.6)</td><td>843 (59.8)</td></tr><tr><td>Chronic obstructive pulmonary disease</td><td>188 (11.9)</td><td>200 (12.6)</td><td>191 (13.5)</td><td>192 (13.6)</td></tr><tr><td>Stroke</td><td>197 (12.5)</td><td>182 (11.5)</td><td>228 (16.1)</td><td>221 (15.7)</td></tr><tr><td>Anemia</td><td>302 (20.4)</td><td>305 (20.4)</td><td>470 (34.9)</td><td>502 (37.9)</td></tr><tr><td>Treatments</td><td></td><td></td><td></td><td></td></tr><tr><td>Beta-blocker</td><td>1,335 (84.8)</td><td>1,369 (86.4)</td><td>1,198 (84.5)</td><td>1,183 (84.0)</td></tr><tr><td>ACEI</td><td>628 (39.9)</td><td>637 (40.2)</td><td>451 (31.8)</td><td>434 (30.8)</td></tr><tr><td>ARB</td><td>515 (32.7)</td><td>523 (33.0)</td><td>529 (37.3)</td><td>529 (37.5)</td></tr><tr><td>ARNI</td><td>144 (9.1)</td><td>161 (10.2)</td><td>111 (7.8)</td><td>96 (6.8)</td></tr><tr><td>SGLT2 inhibitor</td><td>185 (11.7)</td><td>189 (11.9)</td><td>207 (14.6)</td><td>234 (16.6)</td></tr><tr><td>Loop diuretics</td><td>1,361 (86.4)</td><td>1,349 (85.2)</td><td>1,249 (88.1)</td><td>1,267 (89.9)</td></tr></tbody></table>

Values are mean ± SD, n (%), or median (Q1-Q3).

ACEI = angiotensin-converting enzyme inhibitor; AF = atrial fibrillation; ARB = angiotensin receptor blocker; ARNI = angiotensin receptor-nephrilisin inhibitor; BMI = body mass index; eGFR = estimated glomerular filtration rate; HbA1c = hemoglobin A1c; HF = heart failure; KCCQ-TSS = Kansas City Cardiomyopathy Questionnaire total symptom score; LVEF = left ventricular ejection fraction; NT-proBNP = N-terminal pro-B-type natriuretic peptide; SGLT2 = sodium-glucose cotransporter 2; UACR = urine albumin/creatinine ratio.
<table><caption>**TABLE 2** Mean Finerenone/Placebo Dose Within Each eGFR/Dose Stratum During the Trial (mg)</caption><thead><tr><th rowspan="2"></th><th colspan="2">Higher eGFR/High-Dose Stratum</th><th colspan="2">Lower eGFR/Low-Dose Stratum</th></tr><tr><th>Finerenone</th><th>Placebo</th><th>Finerenone</th><th>Placebo</th></tr></thead><tbody><tr><td>Month 1</td><td>26.2 ± 10.6</td><td>27.3 ± 10.9</td><td>13.1 ± 5.6</td><td>13.9 ± 5.7</td></tr><tr><td>Month 3</td><td>32.1 ± 11.8</td><td>34.5 ± 10.5</td><td>15.6 ± 6.3</td><td>16.8 ± 5.9</td></tr><tr><td>Month 6</td><td>33.3 ± 11.7</td><td>35.5 ± 10.3</td><td>16.2 ± 6.2</td><td>17.8 ± 19.5</td></tr><tr><td>Month 9</td><td>33.0 ± 12.1</td><td>35.8 ± 10.1</td><td>15.9 ± 6.5</td><td>17.0 ± 6.0</td></tr><tr><td>Month 12</td><td>33.0 ± 12.2</td><td>35.9 ± 10.0</td><td>15.8 ± 6.5</td><td>17.0 ± 6.0</td></tr><tr><td>Month 24</td><td>32.9 ± 12.2</td><td>35.5 ± 10.4</td><td>15.6 ± 6.8</td><td>17.0 ± 6.1</td></tr><tr><td>Study end</td><td>32.3 ± 9.1</td><td>34.4 ± 7.8</td><td>15.6 ± 4.3</td><td>16.7 ± 4.0</td></tr></tbody></table>

Values are mean ± SD.

Abbreviation as in Table 1.

(finerenone: 1,418; placebo: 1,409). Baseline characteristics were well balanced between treatment assignments within each dose group (Table 1). The mean age was 69 years in the higher eGFR/high-dose stratum and 75 years in the lower eGFR/low-dose stratum, with male patients accounting for 59% and 49%, respectively; the mean LVEF was 52% and 53%, respectively, and most patients were classified as NYHA functional class II (73% vs 65%, respectively).

**ACHIEVED TREATMENT DOSE ACCORDING TO eGFR/DOSE STRATUM.** In patients with higher eGFR/high-dose stratum, the mean achieved dose of placebo was 27.3±10.9 mg/d at 1 month and 34.5±10.5 mg/d at 3 months; for finerenone,

<table><caption>**TABLE 3** Effect of Randomized Treatment on Outcomes by eGFR/Dose Stratum</caption><thead><tr><th rowspan="2"></th><th colspan="2">Higher eGFR/High-Dose Stratum</th><th colspan="2">Lower eGFR/Low-Dose Stratum</th><th rowspan="2">P for Interaction</th></tr><tr><th>Placebo (n = 1,584)</th><th>Finerenone (n = 1,575)</th><th>Placebo (n = 1,409)</th><th>Finerenone (n = 1,418)</th></tr></thead><tbody><tr><td>Primary composite outcome</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Number of events, n</td><td>478</td><td>370</td><td>805</td><td>705</td><td></td></tr><tr><td>Event rate (95% CI)</td><td>12.1 (10.5-13.8)</td><td>9.4 (8.1-10.9)</td><td>24.4 (21.8-27.3)</td><td>21.0 (18.6-23.8)</td><td></td></tr><tr><td>RR (95% CI)<sup>a</sup></td><td colspan="2">0.77 (0.63-0.94)</td><td colspan="2">0.87 (0.74-1.03)</td><td>0.34</td></tr><tr><td>Total HF events</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Number of events, n</td><td>373</td><td>275</td><td>651</td><td>560</td><td></td></tr><tr><td>Event rate (95% CI)</td><td>9.4 (8.0-11.0)</td><td>7.0 (5.9-8.3)</td><td>19.7 (17.4-22.4)</td><td>16.7 (14.5-19.2)</td><td></td></tr><tr><td>RR (95% CI)<sup>a</sup></td><td colspan="2">0.73 (0.58-0.92)</td><td colspan="2">0.86 (0.72-1.03)</td><td>0.27</td></tr><tr><td>Cardiovascular death or first HF event</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Number of events, n (%)</td><td>290 (18.3)</td><td>240 (15.2)</td><td>429 (30.5)</td><td>381 (26.9)</td><td></td></tr><tr><td>Event rate (95% CI)</td><td>7.9 (7.1-8.9)</td><td>6.5 (5.7-7.3)</td><td>15.0 (13.6-16.5)</td><td>12.8 (11.6-14.2)</td><td></td></tr><tr><td>HR (95% CI)<sup>a</sup></td><td colspan="2">0.81 (0.68-0.96)</td><td colspan="2">0.86 (0.75-0.99)</td><td>0.56</td></tr><tr><td>Subdistribution HR (95% CI)<sup>b</sup></td><td colspan="2">0.81 (0.68-0.96)</td><td colspan="2">0.86 (0.75-0.99)</td><td>0.57</td></tr><tr><td>Cardiovascular death</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Number of events, n (%)</td><td>105 (6.6)</td><td>96 (6.1)</td><td>155 (11.0)</td><td>145 (10.2)</td><td></td></tr><tr><td>Event rate (95% CI)</td><td>2.7 (2.2-3.2)</td><td>2.4 (2.0-3.0)</td><td>4.7 (4.0-5.5)</td><td>4.3 (3.7-5.1)</td><td></td></tr><tr><td>HR (95% CI)<sup>a</sup></td><td colspan="2">0.93 (0.70-1.22)</td><td colspan="2">0.92 (0.73-1.15)</td><td>0.96</td></tr><tr><td>Subdistribution HR (95% CI)<sup>b</sup></td><td colspan="2">0.92 (0.70-1.22)</td><td colspan="2">0.91 (0.73-1.14)</td><td>0.96</td></tr><tr><td>First HF event</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Number of events, n (%)</td><td>222 (14.0)</td><td>170 (10.8)</td><td>351 (25.0)</td><td>306 (21.6)</td><td></td></tr><tr><td>Event rate (95% CI)</td><td>6.1 (5.3-6.9)</td><td>4.6 (3.9-5.3)</td><td>12.3 (11.0-13.6)</td><td>10.3 (9.2-11.5)</td><td></td></tr><tr><td>HR (95% CI)<sup>a</sup></td><td colspan="2">0.74 (0.61-0.91)</td><td colspan="2">0.85 (0.73-0.99)</td><td>0.28</td></tr><tr><td>Subdistribution HR (95% CI)<sup>b</sup></td><td colspan="2">0.75 (0.61-0.91)</td><td colspan="2">0.85 (0.74-0.99)</td><td>0.28</td></tr><tr><td>All-cause death</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Number of events, n (%)</td><td>203 (12.8)</td><td>187 (11.9)</td><td>319 (22.6)</td><td>301 (21.2)</td><td></td></tr><tr><td>Event rate (95% CI)</td><td>5.1 (4.5-5.9)</td><td>4.7 (4.1-5.5)</td><td>9.7 (8.7-10.8)</td><td>9.0 (8.0-10.0)</td><td></td></tr><tr><td>HR (95% CI)<sup>a</sup></td><td colspan="2">0.93 (0.76-1.14)</td><td colspan="2">0.92 (0.79-1.08)</td><td>0.95</td></tr><tr><td>Improvement in NYHA functional class from baseline to 12 mo</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Number (%)</td><td>302 (19.1)</td><td>300 (19.1)</td><td>251 (17.8)</td><td>257 (18.1)</td><td></td></tr><tr><td>Odds ratio (95% CI)<sup>a</sup></td><td colspan="2">1.00 (0.84-1.20)</td><td colspan="2">1.02 (0.84-1.23)</td><td>0.91</td></tr><tr><td>Change in KCCQ-TSS from baseline to 12 mo</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Mean change</td><td>6.6 (5.5-7.6)</td><td>7.6 (6.5-8.6)</td><td>6.6 (5.4-7.7)</td><td>9.0 (7.8-10.2)</td><td></td></tr><tr><td>Placebo-corrected difference</td><td colspan="2">1.0 (-0.3-2.2)</td><td colspan="2">2.4 (1.0-3.9)</td><td>0.13</td></tr></tbody></table>

Event rate is the number of events per 100 person-years. NYHA and HRs were estimated using Cox proportional-hazards models, whereas RRs were derived from semiparametric proportional-rates models. <sup>a</sup>Models were stratified by region and baseline LVEF (<60% or ≥60%). <sup>b</sup>Models were adjusted by region and baseline LVEF (<60% or ≥60%).

HF = heart failure; LVEF = left ventricular ejection fraction; RR = rate ratio; other abbreviations as in Table 1.
<caption>FIGURE 1 Cumulative Hazard Estimates of Key Trial Outcomes by eGFR/Dose Stratum and Treatment Assignment</caption>

A Primary outcome

<figure><img src="image_2.png" /></figure>

B Total HF events

<figure><img src="image_3.png" /></figure>

The effect of finerenone compared with placebo on the primary composite point and total heart failure (HF) events by estimated glomerular filtration rate (eGFR)/dose stratum. The LWYY (recurrent events) analysis was stratified by region and baseline left ventricular ejection fraction (<60% or ≥60%). LWYY = Lin-Wei-Yang-Ying.

the respective values were 26.2 ± 10.6 mg/d and 32.1 ± 11.8 mg/d. In both groups, the dose remained stable thereafter. At the trial end, the mean achieved dose was 34.4 ± 7.8 mg for placebo and 32.3 ± 9.1 mg for finerenone (Table 2, Supplemental Figure 1).

In patients with lower eGFR/low-dose stratum, the mean achieved dose of placebo was 13.9 ± 5.7 mg/d at 1 month and 16.8 ± 5.9 mg/d at 3 months; for finerenone, the respective values were 13.1 ± 5.6 mg/d and 15.6 ± 6.3 mg/d. As in the higher eGFR/high-dose stratum, doses remained stable over time, with mean achieved doses at the end of the trial of 16.7 ± 4.0 mg for placebo and 15.6 ± 4.3 mg for finerenone (Table 2, Supplemental Figure 1).

**EFFECT OF FINERENONE ON CLINICAL OUTCOMES ACCORDING TO eGFR/DOSE STRATUM.** The effect of finerenone was consistent across the eGFR/dose strata for the primary endpoint with a ratio rate (RR) of 0.77 [95% CI: 0.63-0.94] among patients in the higher eGFR/high-dose stratum and 0.87 [95% CI: 0.74-1.03] among those in the lower eGFR/low-dose stratum (P for interaction = 0.34), whereas the overall RR was 0.84 [95% CI: 0.74-0.95] (Table 3, Figure 1, Central Illustration). Consistent benefits were observed for the components of the primary outcome, ie, total HF events (RR: 0.73 [95% CI: 0.58-0.92] in the higher eGFR/high-dose stratum vs RR: 0.86 [95% CI: 0.72-1.03] in the lower eGFR/low-dose stratum; P for interaction = 0.27; overall RR: 0.82 [95% CI: 0.71-0.94]), and cardiovascular death (HR: 0.93 [95% CI: 0.70-1.22] in the higher eGFR/high-dose stratum vs HR: 0.92 [95% CI: 0.73-1.15] in the lower eGFR/low-dose stratum; P for interaction = 0.96;

overall HR: 0.93 [95% CI: 0.78-1.11]) (Table 3, Figure 1, Central Illustration). A similar pattern was observed for cardiovascular death or first HF event (P for interaction = 0.56; overall HR: 0.84 [95% CI: 0.76-0.94]), first HF event (P for interaction = 0.28; overall HR: 0.81 [95% CI: 0.72-0.92]), and all-cause death (P for interaction = 0.95; overall HR: 0.93 [95% CI: 0.83-1.06]) (Table 3, Central Illustration). The sub-distribution HRs derived from the Fine-Gray competing risk models were identical or very similar to the cause-specific HRs from the Cox models, and the overall conclusions were unchanged.

Improvement in NYHA functional class from baseline to 12 months did not differ significantly between the finerenone and placebo groups, and there was no significant interaction by eGFR/dose stratum (P for interaction = 0.91).

The mean increase (ie, improvement) in KCCQ-TSS from baseline to 12 months was greater with finerenone compared to placebo, regardless of eGFR/dose stratum (P for interaction = 0.13) (Table 3).

**SAFETY OF FINERENONE ACCORDING TO eGFR/DOSE STRATUM.** In both eGFR/dose strata, the incidence of hyperkalemia, elevated serum creatinine, and hypotension was higher in the finerenone group than in the placebo group, with these differences being consistent across eGFR/dose strata.

Conversely, hypokalemia was more frequently observed in the placebo group compared to the finerenone group in both the eGFR/dose strata, with a statistically significant interaction identified between dose and treatment. The reduction in the odds of hypokalemia was more pronounced in the
## CENTRAL ILLUSTRATION Effect of Finerenone vs Placebo on Outcomes by eGFR/Dose Stratum

<figure><img src="image_4.png" /></figure>

Chimura M, et al. JACC Heart Fail. 2026;■(■):102938.

The effect of finerenone compared with placebo on the primary composite outcome, total heart failure (HF) events, cardiovascular death or a first HF event, cardiovascular death, a first HF event, and all-cause death according to estimated glomerular filtration rate (eGFR)/dose stratum. The LWYY (recurrent events) and Cox (time to first event) models are stratified by region and baseline left ventricular ejection fraction (<60% or ≥60%). LWYY = Lin-Wei-Yang-Ying; RR = rate ratio.

higher eGFR/high-dose stratum compared with the lower eGFR/low-dose stratum (Table 4).

**TEMPORAL CHANGES IN BIOMARKERS ACCORDING TO eGFR/DOSE STRATUM.** From baseline to 12 months, the mean placebo-corrected increase in potassium with finerenone compared to placebo was consistent across eGFR/dose strata (P for interaction = 0.90). For comparison, change of

potassium in the same eGFR strata in RALES, in which the dose of spironolactone was not adjusted for kidney function, are shown in Supplemental Figure 2, where there is a greater increase in potassium among patients in the lower baseline eGFR category compared to the higher eGFR category.

From baseline to 12 months, the mean placebo-corrected reductions in UACR and NT-proBNP with finerenone compared to placebo were consistent
<table><caption>TABLE 4 Laboratory Safety Assessments and Hypotension by eGFR/Dose Stratum</caption><thead><tr><th rowspan="2"></th><th colspan="2">Higher eGFR/High-Dose Stratum</th><th colspan="2">Lower eGFR/Low-Dose Stratum</th><th rowspan="2">P for Interaction</th></tr><tr><th>Finerenone</th><th>Placebo</th><th>Finerenone</th><th>Placebo</th></tr></thead><tbody><tr><td><strong>Hypotension</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Systolic blood pressure &lt;100 mm Hg</td><td>288 (18.7)</td><td>178 (11.5)</td><td>250 (18.2)</td><td>183 (13.4)</td><td></td></tr><tr><td>OR (95% CI)<sup>a</sup></td><td>1.84 (1.48-2.28)</td><td></td><td>1.54 (1.24-1.92)</td><td></td><td>0.28</td></tr><tr><td><strong>Elevated serum creatinine</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>≥2.5 mg/dL</td><td>18 (1.2)</td><td>8 (0.5)</td><td>123 (9.0)</td><td>81 (6.0)</td><td></td></tr><tr><td>OR (95% CI)<sup>a</sup></td><td>2.28 (0.99-5.26)</td><td></td><td>1.59 (1.19-2.13)</td><td></td><td>0.43</td></tr><tr><td>≥3.0 mg/dL</td><td>12 (0.8)</td><td>2 (0.1)</td><td>45 (3.3)</td><td>32 (2.4)</td><td></td></tr><tr><td>OR (95% CI)<sup>a</sup></td><td>6.05 (1.35-27.1)</td><td></td><td>1.42 (0.90-2.26)</td><td></td><td>0.04</td></tr><tr><td><strong>Elevated serum potassium</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>&gt;5.5 mmol/L</td><td>175 (11.4)</td><td>79 (5.1)</td><td>238 (17.5)</td><td>120 (8.9)</td><td></td></tr><tr><td>OR (95% CI)<sup>a</sup></td><td>2.50 (1.89-3.30)</td><td></td><td>2.16 (1.71-2.73)</td><td></td><td>0.48</td></tr><tr><td>&gt;6.0 mmol/L</td><td>38 (2.5)</td><td>13 (0.8)</td><td>48 (3.5)</td><td>28 (2.1)</td><td></td></tr><tr><td>OR (95% CI)<sup>a</sup></td><td>3.10 (1.64-5.86)</td><td></td><td>1.69 (1.05-2.71)</td><td></td><td>0.13</td></tr><tr><td><strong>Decreased serum potassium</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>&lt;3.5 mmol/L</td><td>55 (3.6)</td><td>160 (10.4)</td><td>72 (5.3)</td><td>121 (9.0)</td><td></td></tr><tr><td>OR (95% CI)<sup>a</sup></td><td>0.31 (0.23-0.43)</td><td></td><td>0.57 (0.42-0.77)</td><td></td><td>0.008</td></tr><tr><td>&lt;4.0 mmol/L</td><td>438 (28.5)</td><td>754 (49.0)</td><td>392 (28.8)</td><td>577 (42.7)</td><td></td></tr><tr><td>OR (95% CI)<sup>a</sup></td><td>0.40 (0.34-0.47)</td><td></td><td>0.54 (0.46-0.63)</td><td></td><td>0.01</td></tr></tbody></table>

Values are n (%) or OR (95% CI), unless otherwise indicated. <sup>a</sup>Models were adjusted by region and baseline LVEF (<60% or ≥60%).

OR = odds ratio; other abbreviations as in Tables 1 and 3.

across eGFR/dose strata (P for interaction = 0.65 and 0.17, respectively). In contrast, the mean placebo-corrected decline in eGFR over the same period was significantly greater in the higher eGFR/ high-dose stratum compared with the lower eGFR/ low-dose stratum: 3.86 mL/min/1.73 m² [95% CI: 3.24-4.48 mL/min/1.73 m²] vs 2.68 mL/min/1.73 m² [95% CI: 2.03-3.32 mL/min/1.73 m²]; P for interaction = 0.001 (Figure 2).

DISCUSSION

Dose adjustment based on kidney function is crucial to the safe use of MRAs, although it is important that dose reduction to ensure safety should not compromise efficacy.⁴,¹¹ This balance was achieved in FINEARTS-HF, where the eGFR-based dosing strategy maintained both efficacy and safety as reflected in the comparable reductions in the primary endpoint and similar increases in the risk of hyperkalemia in the higher GFR/high-dose vs lower eGFR/low-dose strata. Although, by definition, patients had very different clinical characteristics in the 2 eGFR/dose strata, the effects of finerenone compared to placebo on all efficacy outcomes, all prespecified safety outcomes, and biomarkers were remarkably similar, with the sole exception of

hypokalemia. The risk of hypokalemia was reduced to a greater degree by finerenone among patients in the higher eGFR/high-dose stratum compared to the lower eGFR/low-dose stratum. Why this was the case is not certain, given that the baseline potassium concentrations in the 2 eGFR/dose strata were similar, as was the risk of hyperkalemia among patients assigned to placebo in each stratum. However, there was a relatively greater decline in eGFR in the higher GFR/high-dose stratum compared with the lower eGFR/low-dose stratum, which could account for a difference in risk of hypokalemia.

The picture related to hyperkalemia was different than for hypokalemia, with a substantially higher risk of hyperkalemia among patients assigned to placebo in the lower eGFR/low-dose stratum compared to the higher GFR/high-dose stratum (8.9% vs 5.1% of patients for potassium >5.5 mmol/L and 2.1% vs 0.8% for potassium >6 mmol/L), yet the relative increase in risk with finerenone was similar in the 2 strata, eg, finerenone vs placebo potassium >5.5 mmol/L OR: 2.16 [95% CI: 1.71-2.73] in the lower eGFR/low-dose stratum vs OR: 2.50 [95% CI: 1.89-3.30] in the higher GFR/high-dose stratum. Indeed, despite the large per-protocol difference in eGFR between these strata (46 vs 75 mL/min/1.73 m²), the mean increase in potassium with finerenone
<figure><img src="image_5.png" /><figcaption>FIGURE 2 Change in Biomarkers According to eGFR/Dose Stratum</figcaption></figure>

The changes in biomarkers according to eGFR/dose stratum. Dots represent geometric means, and error bars represent 95% CIs.

(A) Potassium. (B) eGFR. (C) NT-proBNP. (D) UACR. NT-proBNP = N-terminal pro-B-type natriuretic peptide; UACR = urine albumin/creatinine ratio; other abbreviation as in Figure 1.

after randomization was comparable in the strata. In RALES, dosing was not adjusted according to eGFR and, as shown in **Supplemental Figure 2**, patients with lower eGFR exhibited greater increases in serum potassium concentration than those with preserved eGFR. The eGFR-based dosing strategy in FINEARTS-HF likely played an important role in mitigating the excess risk of hyperkalemia among patients in the lower eGFR/low-dose stratum.

Although there was a relatively greater decline in eGFR in the higher GFR/high-dose stratum compared with the lower eGFR/low-dose stratum, this probably reflects the almost universal finding that eGFR tends to decline more in response to treatment among patients with a higher starting eGFR compared to a lower baseline eGFR.<sup>16-18</sup> Furthermore, the greater decline in patients with a higher starting eGFR may not be clinically meaningful. Likewise, as expected,
the proportion of placebo-treated patients having an increase in creatinine above the thresholds of 2.5 mg/dL and 3.0 mg/dL was larger in the lower eGFR/low-dose stratum. The relative increase in risk with finerenone compared to placebo for the threshold of 2.5 mg/dL was similar in the 2 eGFR/dose strata. Although the risk appeared greater for a creatinine threshold of 3.0 mg/dL in the higher GFR/high-dose stratum compared with the lower eGFR/low-dose stratum, this was likely a spurious observation based on very few patients exceeding this threshold (n = 12 [0.8%] in the finerenone group and n = 2 [0.1%] in the placebo group).

FINEARTS-HF was unique in titrating the dose of finerenone to 40 mg once daily in the higher GFR/high-dose stratum because in the prior trials with this treatment in patients with diabetic kidney disease, the maximum daily dose of finerenone used was 20 mg.<sup>19-26</sup> However, as discussed, the strategy adopted in FINEARTS-HF was both safe and effective and is reflected in the recently updated U.S. Food and Drug Administration-approved product labelling, which recommends titrating to 40 mg daily in patients with a baseline eGFR ≥60 mL/min/1.73 m², potassium and eGFR after 4 weeks permitting (potassium <5.0 mmol/L and eGFR declining <30% compared to the previous value).<sup>27</sup> Using this recommended approach is important as it is unknown whether low-dose finerenone has the same efficacy as higher-dose finerenone in patients with preserved eGFR.

**STUDY LIMITATIONS.** As in other large outcome trials, the prespecified inclusion and exclusion criteria may have limited the enrollment of certain very high-risk patients, such as patients with advanced kidney disease and high baseline potassium concentrations, potentially affecting the generalizability of the results. Moreover, the median follow-up duration was 32 months, which may not be sufficient to fully assess the long-term trajectory of kidney function. Nevertheless, given that eGFR showed an initial decline within 1 month after initiation of finerenone and then remained stable thereafter, dynamic long-term changes attributable to finerenone appear unlikely. Although this is an analysis of subgroups, it was conducted according to a prespecified stratification based on kidney function. This minimizes bias due to differences in kidney function. As this trial was not designed to detect interactions among subgroups, the results of the subgroup analyses may lack statistical reliability and should be interpreted with caution. These findings should be regarded as exploratory, and in the absence of significant interactions, the overall treatment effect should be considered applicable to the subgroups. The

statistical power to detect differences in safety outcomes may also have been limited by the relatively small sample size in each eGFR/dose stratum. Finally, we did not directly compare a uniform fixed-dose regimen across all patients with an eGFR-based dosing strategy. Accordingly, our findings should not be taken as evidence that eGFR-guided dosing is superior to a uniform approach, but rather as demonstrating that the protocol-specified regimen was both effective and safe.

## CONCLUSIONS

In FINEARTS-HF, an eGFR-based dosing strategy maintained both the efficacy and safety of finerenone as reflected in the comparable reductions in the primary endpoint and similar increases in the risk of hyperkalemia in the higher eGFR/high-dose vs lower eGFR/low-dose strata.

**DATA AVAILABILITY** Trial data will be made available by the sponsor, Bayer, in accordance with their data-sharing policy.

## FUNDING SUPPORT AND AUTHOR DISCLOSURES

The FINEARTS-HF trial was funded by Bayer. Dr Chimura has received grants and personal fees from Otsuka Pharma, Daiwa Foundation and the Japan Research Foundation for Clinical Pharmacology. Dr Jhund has received speaker fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, Sun Pharmaceuticals; advisory board fees from AstraZeneca, Boehringer Ingelheim, Novartis; research grants from AstraZeneca, Boehringer Ingelheim, Analog Devices Inc, and Roche Diagnostics; his employer, the University of Glasgow, has been remunerated for clinical trial work from AstraZeneca, Bayer AG, Novartis, and Novo Nordisk; and he serves as Director of GCTP Ltd. Dr Claggett has received consulting fees from Alnylam, Bristol Myers Squibb, Cardior, Cardurion, Corvia, CVRx, Eli Lilly, Intellia, and Rocket; and has served on a data safety monitoring board for Novo Nordisk. Dr Desai has received institutional research grants (to Brigham and Women's Hospital) from Abbott, Alnylam, AstraZeneca, Bayer, Novartis, and Pfizer; and consulting fees from Abbott, Alnylam, AstraZeneca, Bayer, Biofourmis, Boston Scientific, Medpace, Medtronic, Merck, Novartis, Parexel, Porter Health, Regeneron, River2Renal, Roche, Veristat, Verily, and Zydus. Dr Filippatos has received speaker fees, consulting fees, and/or is a committee member of trials and registries sponsored by Bayer, Boehringer Ingelheim, Medtronic, Novartis, Novo Nordisk, Cardior, Servier, Merck, and Vifor Pharma; and research support from the European Union. Dr Gajos has received personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, and Pfizer outside of the submitted work. Dr Brinker, Dr Amarante, Mr Lay-Flurrie, and Dr Rohwedder are full-time employees of Bayer. Dr Lam has received research support from NovoNordisk and Roche Diagnostics; consulting fees from Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Bioethics, 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 cofounder and nonexecutive director of Us2.ai. Dr Sato has received speaker or consulting fees from Otsuka, Novartis Pharma, Daichi Sankyo, Bayer, Boehringer-Ingelheim, Ono, AstraZeneca, Kowa, Taisho, and Terumo. Dr Senni has served on advisory boards and has received consulting and personal fees from Novartis, Abbott, Merck, Merck Sharp & Dohme, Vifor, AstraZeneca, Cardurion, Novo Nordisk, Bayer, and Boehringer Ingelheim. Dr Voors' employer (University Medical Center Groningen) has received consulting fees and/or research support from Adrenomed, Ana-cardio, AstraZeneca, Bayer AG, BMS, Boehringer Ingelheim, Corteria, Eli Lilly, 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, Owkin, Otsuka, Roche Diagnostics, Northsea, and USA2; has stock options at G3Pharmaceutical; has equities at Cereno, Cardiorenal, and Eshmoun Clinical Research; and is the founder of Cardiovascular Clinical Trialists. Dr Yilmaz has received institutional fees from Bayer, Amgen, Novartis, Novo Nordisk, AstraZeneca, Boehringer Ingelheim, and Albert Health; and meeting participation support from Menarini and Roche. Dr Pitt has received consulting fees from Bayer, AstraZeneca, Boehringer Ingelheim, Lexicon, Bristol Myers Squibb, KBP Biosciences, Sarbez Pharmaceuticals, Pharmaceu-ticals, SQinnovations, G3 Pharmaceuticals, Sea Star Medical, Vifor, Prointel, and Brainstorm Medical; and has stock or stock options with KBP Biosciences, Sarbez Pharmaceuticals, Pharmaceu-ticals, SQinnovations, Sea Star Medical, Vifor, Prointel, and Brain-storm Medical; has U.S. Patent 9931412 for site specific delivery of eplerenone to the myocardium; and has a U.S. Patent pending 63/045,783 for histone modulating agents for the prevention and treatment of organ failure. Dr Vaduganathan has received research grant support, served on advisory boards, or had speaker engage-ments with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Bristol Myers Squibb, 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 has participated on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. Dr Solomon has received grants from Alexion, Alnylam, AstraZeneca, Bellerophon,

Bayer, Bristol Myers Squibb, Boston Scientific, Cytokinetics, Edge-wise, Eidos, Gossamer, GlaxoSmithKline, Ionis, Lilly, MyoKardia, National Institutes of Health (NIH)/National Heart Lung and Blood Institute (NHLBI), Novartis, NovoNordisk, Respicardia, Sanofi Pas-teur, Theracos, and Us2.ai; and consulting fees from Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer-Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Ana-cardio, Akros, and Valo. Dr McMurray has received fees to his insti-tution, Glasgow University, for clinical trials and other research projects from the British Heart Foundation, NIH/NHLBI, Alynylam Pharmaceuticals, AstraZeneca, Bayer, Cardurion, Cytokinetics, Novartis, and Roche; consulting fees from Alynylam Pharmaceu-ticals, AnaCardio, AstraZeneca, Bayer, Cardurion, Cytokinetics, Novartis, River BioMedics, Biohaven Pharmaceuticals, Chugai Phar-maceuticals, Protherics Medicine Developments Ltd, DalCor Phar-maceuticals; speaker 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 Pharma-cuticals, 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; has participated in data safety monitoring boards for WCG Clinical Services; and is the Director of Global Clinical Trial Partners Ltd (which provides clinical trial services such as endpoint committees and educational programs). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

ADDRESS FOR CORRESPONDENCE: Dr John J.V. McMurray, British Heart Foundation Cardiovascular Research Centre, University of Glasgow, BHF Glasgow 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** finerenone, heart failure hospitalization, heart failure with mildly reduced ejection fraction, heart failure with preserved ejection fraction, prognosis, renal function stratified dose, treatment effect

**APPENDIX** For supplemental figures, please see the online version of this paper.