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Publications

Journal Article Ahead of print

PubMed: 42244376 DOI: 10.1161/HYPERTENSIONAHA.126.27036

Safety and Synergy of Finerenone and Empagliflozin in Lowering Blood Pressure.

Hypertension

Authors: Rajiv Agarwal, Ricardo Correa-Rotter, Sankar D Navaneethan, Hiddo J L Heerspink, Matthew R Weir, Janet B McGill, Amy K Mottl, Masaomi Nangaku, Julio Rosenstock, Peter Rossing, Muthiah Vaduganathan, Charlie Scott, Li Li, Meike Brinker, Csaba P Kovesdy, Jennifer B Green, Johannes F E Mann

Affiliations

  • Division of Nephrology, Richard L. Roudebush VA Medical Center and Indiana University School of Medicine, Indianapolis, IN (R.A.).
  • Department of Nephrology and Mineral Metabolism, National Medical Science and Nutrition Institute Salvador Zubirán, Mexico City, Mexico (R.C.-R.).
  • Section of Nephrology, Baylor College of Medicine, Houston, TX (S.D.N.).
  • Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, The Netherlands (H.J.L.H.).
  • Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (M.R.W.).
  • Division of Endocrinology, Metabolism and Lipid Research, Washington University in St. Louis, School of Medicine, St. Louis, MO (J.B.M).
  • University of North Carolina Kidney Center, UNC School of Medicine, Chapel Hill, NC (A.K.M.).
  • Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan (M.N.).
  • University of Texas Southwestern Medical Center, Dallas, TX (J.R.).
  • Steno Diabetes Center Copenhagen, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark (P.R.).
  • Division of Cardiovascular Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA (M.V.).
  • Clinical Statistics and Analytics, Bayer US LLC, Whippany, NJ (C.S.).
  • Global Medical Evidence, Bayer AG, Berlin, Germany (L.L.).
  • Cardiology and Nephrology Clinical Development, Bayer AG, Berlin, Germany (M.B.).
  • Division of Nephrology, The University of Tennessee Health Science Center, Memphis, TN (C.P.K.).
  • Division of Endocrinology, Department of Medicine and Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (J.B.G.).
  • KfH Kidney Centre, Munich, and Department of Nephrology and Hypertension, Friedrich Alexander University, Erlangen, Germany (J.F.E.M.).

Abstract

BACKGROUND

This secondary analysis of the CONFIDENCE (combination effect of fInerenone and empagliflozin in participants with chronic kidney disease and type 2 diabetes using a UACR endpoint) trial (REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05254002) assessed systolic blood pressure (SBP) changes with empagliflozin/finerenone combination therapy versus monotherapy in people with chronic kidney disease and type 2 diabetes across baseline SBP categories. We assessed SBP response predictors and whether early (day 30) SBP changes mediate urinary albumin-to-creatinine ratio reductions.

METHODS

Participants (n=800) were stratified by baseline SBP (<130 mm Hg; ≥130 mm Hg). Outcomes included SBP response (≥10 mm Hg reduction from baseline at day 180) and longitudinal SBP changes, analyzed by linear mixed-effects models and logistic regression. Causal mediation analysis, a secondary exploratory analysis, evaluated the effect of day 30 SBP change on day 180 urinary albumin-to-creatinine ratio reduction.

RESULTS

At baseline, 532 (66%) participants had SBP ≥130 mm Hg; 268 (34%) had SBP <130 mm Hg. Combination therapy increased SBP response odds versus finerenone (odds ratio, 1.83 [95% CI, 1.21-2.76]; P=0.004) or empagliflozin (odds ratio, 1.45 [95% CI, 0.97-2.17]; P=0.07). The strongest predictor of response was baseline SBP (odds ratio, 2.04 per 10 mm Hg higher SBP; P<0.0001). Combination therapy significantly reduced SBP versus monotherapies in the ≥130 mm Hg (P<0.0001) but not in the <130 mm Hg group. SBP reduction mediated <10% of the total urinary albumin-to-creatinine ratio reduction. Acute kidney injury and hyperkalemia incidences were similar across SBP subgroups.

CONCLUSIONS

Combination therapy reduced SBP more than monotherapies in participants with SBP ≥130 mm Hg. Urinary albumin-to-creatinine ratio reduction appeared largely independent of SBP changes at day 30; though this secondary analysis was limited by reliance on clinic blood pressure measurement. Prospective studies with ambulatory blood pressure monitoring are required.

MeSH

Diabetes Mellitus, Kidney Diseases, Creatinine, Safety, Blood, Albuminuria, Blood Pressure, Kidney, Odds Ratio, Therapeutics, Mediation Analysis, Hemodynamics, Diabetes Mellitus, Type 2