Effect of finerenone on ambulatory blood pressure in chronic kidney disease in type 2 diabetes

Abstract

Objective: Finerenone is a selective nonsteroidal mineralocorticoid receptor antagonist with a short half-life. Its effects on cardiorenal outcomes were thought to be mediated primarily via nonhemodynamic pathways, but office blood pressure (BP) measurements were insufficient to fully assess hemodynamic effects. This analysis assessed the effects of finerenone on 24-h ambulatory BP in patients with chronic kidney disease and type 2 diabetes.

Methods: ARTS-DN (NCT01874431) was a phase 2b trial that randomized 823 patients with type 2 diabetes and chronic kidney disease, with urine albumin-to-creatinine ratio ≥30 mg/g and estimated glomerular filtration rate of 30-90 ml/min per 1.73 m2 to placebo or finerenone (1.25-20 mg once daily in the morning) administered over 90 days. Ambulatory BP monitoring (ABPM) over 24 h was performed in a subset of 240 patients at screening, Day 60, and Day 90.

Results: Placebo-adjusted change in 24-h ABPM systolic BP (SBP) at Day 90 was -8.3 mmHg (95% confidence interval [CI], -16.6 to 0.1) for finerenone 10 mg (n = 27), -11.2 mmHg (95% CI, -18.8 to -3.6) for finerenone 15 mg (n = 34), and -9.9 mmHg (95% CI, -17.7 to -2.0) for finerenone 20 mg (n = 31). Mean daytime and night-time SBP recordings were similarly reduced and finerenone did not increase the incidence of SBP dipping. Finerenone produced a persistent reduction in SBP over the entire 24-h interval.

Conclusions: Finerenone reduced 24-h, daytime, and night-time SBP. Despite a short half-life, changes in BP were persistent over 24 h with once-daily dosing in the morning.

Graphical abstract

FIGURE 1

Time course of change in office SBP. Change in office SBP from baseline to Day 120 with finerenone compared with placebo. Mixed model analysis with factors treatment group, time, baseline value, and treatment ∗ time interaction as covariates. Data are expressed as LS mean change from baseline ± 95% CI. CI, confidence interval; LS, least-squares; SBP, systolic blood pressure.

FIGURE 2

LS mean change from baseline in 24-h ABPM SBP at Day 60 and Day 90 using multiple imputation. Reduction in SBP was observed for 24-h ABPM with finerenone ≥10 mg relative to baseline. Mixed model analysis with factors treatment group, time, baseline value, and treatment ∗ time interaction as covariates. LS mean change from baseline with 95% CI. Missing data at Day 60 and Day 90 are imputed with multiple imputation for ABPM analyses. ^∗P < 0.05; ^†P < 0.01. ABPM, ambulatory blood pressure monitoring; CI, confidence interval; LS, least-squares; SBP, systolic blood pressure.

FIGURE 3

Scatterplot of average 24-h SBP by ABPM at screening and change from screening to Day 90. Individual patient data from 24-h ABPM measurements at screening and Day 90. One patient who was treated with placebo was excluded from the analysis because of a change in ABPM that was deemed outside of a clinically plausible range (SBP of 121.3 mmHg at screening and an increase in SBP of 72.2 mmHg at Day 90). ABPM, ambulatory blood pressure monitoring; SBP, systolic blood pressure.

FIGURE 4

Change in SBP over 24 h recorded by ABPM. Change in SBP as recording by ABPM in patients treated with placebo (n = 16) (a), finerenone 10 mg (n = 17) (b), finerenone 15 mg (n = 24) (c), and finerenone 20 mg (n = 18) (d). Mean SBP at hourly intervals demonstrated a similar pattern in SBP across treatment groups at screening, with lower nocturnal than daytime SBP. Reduction in SBP with finerenone at Day 90 was persistent across all time points and was generally below that of the mean screening values. ABPM, ambulatory blood pressure monitoring; SBP, systolic blood pressure; SE, standard error.