Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes

Abstract

Background: The FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) evaluated the effect of the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone on kidney and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes with optimized renin-angiotensin system blockade. Compared with placebo, finerenone reduced the composite kidney and cardiovascular outcomes. We report the effect of finerenone on individual cardiovascular outcomes and in patients with and without history of atherosclerotic cardiovascular disease (CVD).

Methods: This randomized, double-blind, placebo-controlled trial included patients with type 2 diabetes and urine albumin-to-creatinine ratio 30 to 5000 mg/g and an estimated glomerular filtration rate ≥25 to <75 mL per min per 1.73 m², treated with optimized renin-angiotensin system blockade. Patients with a history of heart failure with reduced ejection fraction were excluded. Patients were randomized 1:1 to receive finerenone or placebo. The composite cardiovascular outcome included time to cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. Prespecified cardiovascular analyses included analyses of the components of this composite and outcomes according to CVD history at baseline.

Results: Between September 2015 and June 2018, 13 911 patients were screened and 5674 were randomized; 45.9% of patients had CVD at baseline. Over a median follow-up of 2.6 years (interquartile range, 2.0-3.4 years), finerenone reduced the risk of the composite cardiovascular outcome compared with placebo (hazard ratio, 0.86 [95% CI, 0.75-0.99]; P=0.034), with no significant interaction between patients with and without CVD (hazard ratio, 0.85 [95% CI, 0.71-1.01] in patients with a history of CVD; hazard ratio, 0.86 [95% CI, 0.68-1.08] in patients without a history of CVD; P value for interaction, 0.85). The incidence of treatment-emergent adverse events was similar between treatment arms, with a low incidence of hyperkalemia-related permanent treatment discontinuation (2.3% with finerenone versus 0.8% with placebo in patients with CVD and 2.2% with finerenone versus 1.0% with placebo in patients without CVD).

Conclusions: Among patients with chronic kidney disease and type 2 diabetes, finerenone reduced incidence of the composite cardiovascular outcome, with no evidence of differences in treatment effect based on preexisting CVD status. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02540993.

Keywords: cardiovascular disease; chronic kidney disease; clinical trial; finerenone; mineralocorticoid receptor; primary and secondary prevention; type 2 diabetes.

Figure 1.

Composite cardiovascular outcome. Time to first onset of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Reproduced from Bakris et al with permission. Copyright © 2020, Massachusetts Medical Society.

Figure 2.

Components of the composite cardiovascular outcome. A, Time to first onset of cardiovascular death. B, Time to first onset of nonfatal myocardial infarction. C, Time to first onset of nonfatal stroke. D, Time to first onset of hospitalization for heart failure.

Figure 3.

Composite cardiovascular outcome in patients with and without history of CVD. A, The composite cardiovascular outcome of time to first onset of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure in patients with a history of CVD at baseline. B, The composite cardiovascular outcome in patients without a history of CVD at baseline. CVD indicates cardiovascular disease.

Figure 4.

Composite cardiovascular outcome in subgroups of history of CVD. CVD indicates cardiovascular disease; MI, myocardial infarction; and PY, patient-year.

Figure 5.

Composite kidney outcome according to history of CVD. A, The composite kidney outcome of time to first onset of kidney failure, a sustained ≥40% decrease in estimated glomerular filtration rate from baseline over at least 4 weeks, or renal death, in patients with a history of CVD at baseline. B, The primary outcome in patients without a history of CVD at baseline. CVD indicates cardiovascular disease.

Figure 6.

Effects on UACR over time in patients with and without history of CVD. A, The effects of finerenone and placebo on the UACR in patients with a history of CVD at baseline. B, Effects on UACR in patients without a history of CVD at baseline. Data are least squares (LS)–mean and 95% CI presented on a logarithmic scale. CVD indicates cardiovascular disease; and UACR, urine albumin-to-creatinine ratio.