Blood Pressure and Cardiorenal Outcomes With Finerenone in Chronic Kidney Disease in Type 2 Diabetes

Abstract

Background: Chronic kidney disease is frequently associated with hypertension and poorly controlled blood pressure can lead to chronic kidney disease progression. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, significantly improves cardiorenal outcomes in patients with chronic kidney disease and type 2 diabetes. This analysis explored the relationship between office systolic blood pressure (SBP) and cardiorenal outcomes with finerenone in FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease).

Methods: Patients with type 2 diabetes, urine albumin-to-creatinine ratio 30 to 5000 mg/g, and estimated glomerular filtration rate of 25 to <75 mL/min per 1.73 m² receiving optimized renin-angiotensin system blockade, were randomized to finerenone or placebo. For this analysis, patients (N=5669) were grouped by baseline office SBP quartiles.

Results: Finerenone reduced office SBP across the baseline office SBP quartiles, including patients with baseline office SBP of >148 mm Hg. Overall, patients with lower baseline office SBP quartile and greater declines from baseline in SBP were associated with better cardiorenal outcomes. The risk of primary kidney and key secondary cardiovascular composite outcomes was consistently reduced with finerenone versus placebo irrespective of baseline office SBP quartiles (P for interaction 0.87 and 0.78, respectively). A time-varying analysis revealed that 13.8% and 12.6% of the treatment effect with finerenone was attributed to the change in office SBP for the primary kidney composite outcome and the key secondary cardiovascular outcome, respectively.

Conclusions: In FIDELIO-DKD, cardiorenal outcomes improved with finerenone irrespective of baseline office SBP. Reductions in office SBP accounted for a small proportion of the treatment effect on cardiorenal outcomes.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT02540993.

Keywords: blood pressure; chronic kidney diseases; finerenone; mineralocorticoid receptor antagonist; systolic blood pressure; type 2 diabetes.

Figure 1.

Change in office systolic blood pressure (SBP) and office diastolic blood pressure (DBP) over the course of FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease). Effect of finerenone and placebo on (A) office SBP and (B) office DBP. A modest and consistent reduction in office SBP was observed with finerenone compared with placebo. There was also a slight reduction in office DBP with finerenone compared with placebo over the duration of the trial. Data expressed as mean (SD). Overall least squares (LS) mean difference is provided for the change from baseline.

Figure 2.

Change in office systolic blood pressure (SBP) by baseline office SBP quartiles during FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease). Effect of finerenone and placebo on office SBP by office SBP quartile at baseline. Data expressed as least squares (LS) mean (±95% CI). Overall LS mean difference is provided. Q indicates quartile.

Figure 3.

Primary and key secondary outcomes by baseline office systolic blood pressure (SBP) quartile. Effect of finerenone on kidney and cardiovascular (CV) outcomes across baseline office SBP quartiles. A similar benefit was observed for the primary kidney composite (time to first occurrence of kidney failure, sustained estimated glomerular filtration rate (eGFR) decline ≥40% from baseline over 4 weeks or more, or renal death), the key secondary CV composite (time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and the secondary kidney composite (time to first occurrence of kidney failure, a sustained decrease of at least 57% in eGFR from baseline over 4 weeks or more, or renal death) outcomes. PY indicates patient-years; and Q, quartile.