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

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.