Becca Sauter, PharmD, St. Cloud Veterans Affairs Medical Center
Background: It has long been established that control of blood pressure (BP) decreases risk for cardiovascular events and decline of renal function. This is also true for people with type 2 diabetes (T2DM), who are at a higher risk for cardiovascular related events. Finerenone is a mineralocorticoid receptor antagonist that is currently approved to reduce the risk of sustained eGFR decline, end-stage renal disease, cardiovascular death, non-fatal myocardial infarction, and hospitalizations for heart failure in patients with chronic kidney disease (CKD) and associated T2DM at daily doses of 10 or 20 mg. However the impact of finerenone on blood pressure in patients with T2DM and CKD is unknown.
Objective: To investigate the effect of finerenone on ambulatory BP to evaluate the 24-hour profile, and compare to the time course of concurrently obtained office blood pressure in patients with CKD and T2DM.
Study Design: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b study. A total of 840 participants were randomized to the finerenone (1.25- 20 mg daily) or placebo group. A subset of 240 patients were randomly selected to obtain 24-hour ambulatory blood pressure at screening, day 60 and day 90 of the study. Participants needed to be taking at least the minimum recommended dose of a renin-angiotensin system inhibitor prior to screening, have a diagnosis of T2DM, urine albumin-to-creatinine ratio (UACR) >30 mg/g, eGFR >30 mL/min per 1.73 m^2, and a serum potassium level < 4.8 mmol/L at screening. BP was measured three times with the participant in a sitting position at the screening, day 60, and day 90 visits. For a small subset of patients, 24-hour ambulatory BP was taken at the screening visit, day 60 and day 90. Missing values for ambulatory BP readings were imputed with multiple imputation using baseline/intake values- which cannot guarantee that simulated data would be replicated. Least-squares mean treatment differences between finerenone and placebo groups were performed along with 95% confidence intervals.
Results: Finerenone reduced the 24-hour ambulatory BP with significance at day 60 for those taking 10 mg (-7.3 mmHg, 95% CI, -13 to -1.6) and 15 mg (-8.9 mmHg, 95% CI, -13 to -4.7) daily of finerenone compared to those taking placebo. It also reduced ambulatory BP with significance at day 90 for those taking 15 mg (-8.7 mmHg, 95% CI, -12.8 to -4.5) and 20 mg (-7.4 mmHg, 95% CI, -11.7 to -3) daily of finerenone when compared to placebo. Regarding change in office BP readings, there was a statistical difference between placebo and some doses of finerenone- however differences did not correlate with doses nor were office readings consistent. Comparison between office SBP and ambulatory BP showed no statistical differences in the treatment group.
Conclusion: Finerenone decreased 24-hour ambulatory BP in patients with CKD and T2DM.
Key Point: Finerenone has a short half-life and still decreased overall blood pressure in patients with T2DM and CKD suggesting that there may be more effects that finerenone has going beyond the pharmacokinetic profile. This study did have a few weaknesses with its relatively small sample size, short time frame, and input of missing data. However, its design to study BP effects in this patient population is still valuable, indicating that future investigation of finerenone may have a larger impact on clinical outcomes.
References:
- Agarwal, R., Ruilope, L., Ruiz-Hurtado, G., Haller, H., Schmieder, R., Anker, S., Filippatos, G., Pit, B., Rossing, P., Lambert, M., Nowack, C., Kolkhof, P., Joseph, A., Bakris, G. Effect of finerenone on ambulatory blood pressure in chronic kidney disease in type 2 diabetes. Journal of Hypertension 41:2, 295-302. February 2023.
- Finerenone: Drug information. UpToDate. Wolters Kluwer.