Finerenone-Empagliflozin Combination Therapy in Apparent Resistant Hypertension

@article{rajivagarwal2026finerenoneempagliflozin,
  title = {{Finerenone-Empagliflozin Combination Therapy in Apparent Resistant Hypertension}},
  author = {Rajiv Agarwal, MD, MS and Sankar D. Navaneethan, MD, MS, MPH and Ricardo Correa-Rotter, MD and Michelle M. Estrella, MD, MHS and Hiddo J.L. Heerspink, PhD and Janet B. McGill, MD and Amy K. Mottl, MD and Masaomi Nangaku, MD, PhD and Julio Rosenstock, MD and Peter Rossing, MD and Muthiah Vaduganathan, MD, MPH and Javier Morales, MD and Yehuda Handelsman, MD and Jennifer B. Green, MD and Johannes F.E. Mann, MD and Charlie Scott, MSc and Li Li, MD, MBA and Meike Brinker, MD and Matthew R. Weir, MD},
  journal = {JACC: Advances},
  year = {2026},
  month = oct,
  doi = {10.1016/j.jacadv.2026.103388},
  url = {https://doi.org/10.1016/j.jacadv.2026.103388},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Finerenone-Empagliflozin Combination Therapy in Apparent Resistant Hypertension
AU  - Rajiv Agarwal, MD, MS
AU  - Sankar D. Navaneethan, MD, MS, MPH
AU  - Ricardo Correa-Rotter, MD
AU  - Michelle M. Estrella, MD, MHS
AU  - Hiddo J.L. Heerspink, PhD
AU  - Janet B. McGill, MD
AU  - Amy K. Mottl, MD
AU  - Masaomi Nangaku, MD, PhD
AU  - Julio Rosenstock, MD
AU  - Peter Rossing, MD
AU  - Muthiah Vaduganathan, MD, MPH
AU  - Javier Morales, MD
AU  - Yehuda Handelsman, MD
AU  - Jennifer B. Green, MD
AU  - Johannes F.E. Mann, MD
AU  - Charlie Scott, MSc
AU  - Li Li, MD, MBA
AU  - Meike Brinker, MD
AU  - Matthew R. Weir, MD
PY  - 2026
DA  - 2026/10/23
JO  - JACC: Advances
DO  - 10.1016/j.jacadv.2026.103388
UR  - https://doi.org/10.1016/j.jacadv.2026.103388
AB  - 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 m 2 ). 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 m 2 ; 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.
SN  - 2772-963X
ER  -