Finerenone-Empagliflozin Combination Therapy in Apparent Resistant Hypertension: A CONFIDENCE Trial Post Hoc Analysis

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.

This analysis assessed whether finerenone plus empagliflozin lowers blood pressure (BP) meaningfully in aTRH, and whether aTRH modifies these agents' efficacy and safety.

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.

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%).

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.