Systolic Blood Pressure Variability and Finerenone Benefit in CKD and Type 2 Diabetes: A FIDELITY Post Hoc Analysis

Presenter: S Rajagopalan 

High visit-to-visit systolic blood pressure (SBP) variability is associated with increased risks of cardiovascular (CV) and chronic kidney disease (CKD) outcomes, as well as increased aldosterone and mineralocorticoid receptor activation. A post hoc subanalysis of the FIDELITY pooled dataset from FIDELIO-DKD and FIGARO-DKD evaluated the association between SBP variability and CV and kidney outcomes, and whether variability modified the effect of the non-steroidal mineralocorticoid receptor antagonist finerenone in patients with CKD and type 2 diabetes. Higher pre-treatment SBP variability was associated with increased risks of CV and kidney events in both treatment groups. Over a median 3 years, finerenone reduced composite CV (HR 0.86; 95% CI 0.78–0.95) and kidney outcomes (HR 0.76; 95% CI 0.66–0.88) versus placebo across SBP-variability quartiles, with a trend toward greater CV benefit at the highest variability (HR 0.72; 95% CI 0.60–0.87). Finerenone's treatment effect was not modified by SBP variability, with comparable safety to placebo.

Finerenone in Real-World CKD and Type 2 Diabetes: Cardiovascular Effectiveness and Hyperkalaemia Risk 

Presenter: S Rao
Although pivotal trials have established the efficacy of finerenone, real-world evidence on its cardiovascular effectiveness and safety in chronic kidney disease (CKD) with type 2 diabetes (T2D) has been limited. A new-user cohort study using linked US claims, electronic health records and laboratory data compared 14,287 finerenone initiators with 57,148 propensity-score-matched nonusers (mean age 66 years; 53% male). Finerenone initiators had a lower risk of the composite cardiovascular outcome of acute myocardial infarction or heart failure (HF) hospitalisation (HR 0.89; 95% CI 0.79–1.00), driven by fewer HF hospitalisations (HR 0.84; 95% CI 0.73–0.96). Risks of myocardial infarction, new-onset HF and all-cause mortality were attenuated or null, while hyperkalaemia was more frequent with finerenone (HR 1.47; 95% CI 1.31–1.65). The findings support an association between finerenone use and lower HF hospitalisation risk in routine practice, alongside an increased risk of hyperkalaemia.

Body Weight and Cardiorenal-Metabolic Effects of Finerenone, Empagliflozin, or Their Combination by BMI in CKD and Type 2 Diabetes: A CONFIDENCE Analysis 

Presenter: J Ostrominski

Obesity is associated with the onset and progression of both type 2 diabetes and chronic kidney disease, yet whether it modifies the benefits of empagliflozin, finerenone, or their combination on cardiovascular-kidney-metabolic parameters was unclear. An exploratory analysis of the CONFIDENCE trial (800 participants) assessed effects on body weight and whether baseline body mass index (BMI) modified treatment responses. Body weight declined across all treatment groups, with greater reductions versus finerenone alone among those receiving empagliflozin (−1.0 kg; 95% CI −1.2 to −0.7) or combination therapy (−1.0 kg; 95% CI −1.3 to −0.8), compared with −0.5 kg (95% CI −0.8 to −0.2) with finerenone. Higher BMI was associated with greater weight loss with empagliflozin-containing regimens. BMI did not modify treatment effects on urine albumin-to-creatinine ratio, estimated glomerular filtration rate or glycated haemoglobin, although systolic blood pressure reductions with empagliflozin and combination therapy were greater at higher BMI. The findings support combining empagliflozin and finerenone to maximise albuminuria reduction regardless of BMI, with weight loss as a potential additional benefit. 

Early eGFR Decline and Urinary Tubular-Injury Biomarkers with Finerenone in CKD and Type 2 Diabetes: The FIVE-STAR Trial 

Presenter: M Vaduganathan

Guideline-recommended cardio-kidney-metabolic therapies can cause early declines in estimated glomerular filtration rate (eGFR), which may raise concern for acute kidney injury and lead to premature treatment discontinuation. The FIVE-STAR trial was a 24-week, double-blind comparison of finerenone 10 or 20 mg versus placebo in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), designed to assess whether early eGFR declines were accompanied by changes in urinary markers of tubular injury. Among 101 participants, 24 (24%) experienced an eGFR decline >10% from baseline to week 4, more frequently with finerenone (17 vs 7 with placebo). An initial eGFR decline did not modify finerenone’s effects on any of seven urinary biomarkers of tubular injury (all Pinteraction>0.05). Among participants with an early decline, finerenone did not significantly alter L-FABP, NAG, NGAL, β2-microglobulin, α1-microglobulin, type IV collagen or pentosidine versus placebo (all P>0.05). The absence of biomarker evidence of tubular injury provides reassurance that early eGFR declines with finerenone should not automatically prompt treatment interruption or discontinuation.

Finerenone Versus Steroidal MRAs Across Heart Failure, CKD and Metabolic Disease: Real-World Comparative Outcomes

Presenter: A Briasoulis

Mineralocorticoid receptor antagonists (MRAs) are central to cardiorenal therapy, but comparative evidence across different clinical phenotypes remains limited. A real-world TriNetX analysis compared spironolactone and eplerenone with finerenone, the latter initiated alongside sodium-glucose cotransporter-2 inhibitors (SGLT2i), across propensity-matched cohorts with heart failure (HF) with reduced or preserved ejection fraction (HFrEF/HFpEF), chronic kidney disease (CKD), diabetes mellitus (DM) and non-DM. In HF, finerenone was associated with fewer HF events than steroidal MRAs in HFrEF (HR 0.75; 95% CI 0.67–0.85) and HFpEF (HR 0.62; 95% CI 0.56–0.68), without a significant survival difference and with a trend toward higher hyperkalaemia risk. In CKD, finerenone was associated with lower mortality (HR 0.38; 95% CI 0.32–0.45) and adapted-MACE (HR 0.45; 95% CI 0.39–0.52), alongside lower acute kidney injury risk. These hypothesis-generating findings support phenotype-driven MRA selection, pending prospective confirmation.

ESC Congress 2026, 28 - 31 Aug, Munich, Germany