Finerenone-Empagliflozin Combination Therapy in Apparent Resistant Hypertension: A CONFIDENCE Trial Post Hoc Analysis
In brief
Finerenone plus empagliflozin lowered blood pressure more in resistant hypertension
In this post hoc analysis of 796 adults with kidney disease and type 2 diabetes, 307 had apparent resistant hypertension; the combination lowered systolic blood pressure more than either drug alone. Those with resistant hypertension were more likely to have a drop of at least 10 mm Hg, but the analysis did not compare treatment directly with spironolactone, and the findings need confirmation.
- Journal
- JACC. Advances (Q1)
- Published
- 23 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Rajiv Agarwal, Sankar D Navaneethan, Ricardo Correa-Rotter, Michelle M Estrella, Hiddo J L Heerspink, Janet B McGill, et al.
- PMID
- 42914747
- DOI
- 10.1016/j.jacadv.2026.103388
Why clinicians should know about it
- Picked for Nephrology (top studies of the week, 25 October 2026): Post hoc analysis shows BP reduction with finerenone‑empagliflozin
Abstract
BACKGROUND: Apparent treatment-resistant hypertension (aTRH) is common in chronic kidney disease (CKD) with type 2 diabetes and predicts worse outcomes. Spironolactone, the established fourth-line agent, is limited by hyperkalemia in CKD. OBJECTIVES: This analysis assessed whether finerenone plus empagliflozin lowers blood pressure (BP) meaningfully in aTRH, and whether aTRH modifies these agents' efficacy and safety. METHODS: Post hoc analysis of CONFIDENCE (NCT05254002), a double-blind randomized trial of finerenone, empagliflozin, or both in CKD with albuminuria and type 2 diabetes. aTRH was BP ≥130/80 mm Hg on 3 antihypertensive drugs, or ≥4 drugs regardless of BP. Mixed models and logistic regression identified predictors of BP response. RESULTS: Of the 796 participants, 307 (39%) had aTRH; they were older, more obese, and had more atherosclerotic cardiovascular disease, higher albuminuria, and higher systolic BP (140.9 vs 131.5 mm Hg) but similar estimated glomerular filtration rate (53 vs 55 mL/min/1.73 m2). Combination therapy lowered systolic BP more than either monotherapy. Independent predictors of a ≥10 mm Hg systolic BP fall were aTRH (OR: 1.56; 95% CI: 1.08-2.25) and higher baseline estimated glomerular filtration rate (OR: 1.15 per 10 mL/min/1.73 m2; 95% CI: 1.05-1.26); diuretic use and albuminuria were not. The aTRH effect was treatment-independent (interaction P = 0.21). Adverse events were more frequent with aTRH (63.8% vs 51.1%), yet on combination therapy hyperkalemia was less frequent (11.2% vs 17.5%). CONCLUSIONS: aTRH affected approximately 40% of participants and marked a higher-risk phenotype responsive to finerenone-empagliflozin, with BP reductions comparable to spironolactone but without the excess hyperkalemia that limits its use in CKD.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.