Ambulatory SBP reduction with nonsteroidal MRA in patients with T2DM and CKD
Effect of finerenone on ambulatory blood pressure in chronic kidney disease in type 2 diabetes
Introduction and methods
Background
The phase 3 trials FIDELIO-DKD and FIGARO-DKD recently showed that the selective, nonsteroidal MRA finerenone delayed progression of CKD and reduced the risk of CV events in patients with both T2DM and CKD [1,2]. The hemodynamic effects of finerenone are not clear as blood pressure (BP) data were limited to office measurements in these trials and few other data on this subject exist.
Aim of the study
The authors investigated the effect of finerenone ≥10 mg on 24-hour ambulatory BP and compared this outcome to the time course of concurrently obtained office BP in patients with T2DM and CKD.
Methods
The ARTS-DN (Mineralocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy) trial was a multicenter, double-blind, placebo-controlled, dose-finding, parallel-group, phase 2b RCT in which 821 patients with T2DM, urine albumin-to-creatinine ratio ≥30 mg/g, and eGFR 30–90 mL/min per 1.73 m²were randomized to finerenone 1.25–20 mg or placebo (once daily in the morning) for 90 days [3]. The primary aim of this trial was to assess the effects of finerenone on albuminuria. The current substudy analysis included a subset of patients for whom ambulatory BP measurements were available (n=240).
24-hour ambulatory BP monitoring (ABPM) was performed at screening and at 60 and 90 days. Office BP measurements were conducted at baseline, at 1, 7, 30, 60 and 90 days, and at the follow-up visit (after 120 days).
Main results
Change in office systolic BP
- For patients taking finerenone 10 mg (n=27), the placebo-adjusted change in office systolic BP (SBP) from baseline to 60 days was –4.3 mmHg (95%CI: –10.6 to 2.1) and from baseline to 90 days –1.4 mmHg (95%CI: –6.8 to 4.0). These placebo-adjusted changes were –7.1 mmHg (95%CI: –12.6 to –1.6) and –6.5 mmHg (95%CI: –11.4 to –1.5), respectively, for patients taking finerenone 15 mg (n=34)and–5.4 mmHg (95%CI: –12.0 to 1.1) and –3.6 mmHg (95%CI: –9.2 to 2.0), respectively, for those on finerenone 20 mg (n=31).
- At the follow-up visit, smaller differences in placebo-adjusted change in office SBP were found: –0.2 mmHg (95%CI: –7.1 to 6.7), –3.0 mmHg (95%CI: –9.0 to 3.1), and 0.1 mmHg (95%CI: –6.0 to 6.3) for finerenone 10 mg, 15 mg, and 20 mg, respectively.
Changes in 24-hour, daytime, and nighttime ambulatory systolic BP
- The placebo-adjusted changes in 24-hour ABPM SBP were –9.8 mmHg (95%CI: –18.0 to –1.6) at 60 days and –8.3 mmHg (95%CI: –16.6 to 0.1) at 90 days for patients taking finerenone 10 mg; –11.4 mmHg (95%CI: –18.5 to –4.3) and –11.2 mmHg (95%CI: –18.8 to –3.6), respectively, for those taking finerenone 15 mg; and –6.4 mmHg (95%CI: –13.6 to 0.9) and –9.9 mmHg (95%CI: –17.7 to –2.0), respectively, for those on finerenone 20 mg.
- For daytime and nighttime ABPM SBP, similar placebo-adjusted changes were observed.
- There were no statistically significant differences in changes from baseline to 90 days between office and ABPM SBP by treatment group.
24-hour time course of ambulatory systolic BP
- At screening, mean SBP at hourly intervals showed a similar pattern across treatment groups, with SBP being lower at night than during the day.
- At 90 days, the magnitude of the SBP reduction with finerenone was persistent at almost all time points, whereas the placebo group showed a similar mean SBP as seen at screening.
- No significant differences in the effect of placebo or finerenone on ABPM SBP were found between daytime and nighttime.
- There was no evidence for an increase the incidence of nocturnal SBP dipping in patients treated with finerenone compared with placebo .
Conclusion
This substudy analysis of the ARTS-DN trial in 240 patients with T2DM and CKD showed that finerenone (dosed once daily in the morning) reduced 24-hour, daytime, and nighttime SBP from baseline to 60 and/or 90 days compared with placebo. Although finerenone has a short plasma half-life (~2–3 hours) and no active metabolites, the SBP reductions at 90 days were persistent over 24 hours, including during the night.
According to the authors, their results suggested “finerenone has hemodynamic effects in patients with CKD and T2D[M] that are unlikely to be attributable to its pharmacokinetic properties. These hemodynamic effects provide a biological basis for greater incidence of hypotension, a lower incidence of hypertension, and an early separation in curves of the time to first CV events seen with finerenone.”
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