Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis

Abstract

Aims: The complementary studies FIDELIO-DKD and FIGARO-DKD in patients with type 2 diabetes and chronic kidney disease (CKD) examined cardiovascular and kidney outcomes in different, overlapping stages of CKD. The purpose of the FIDELITY analysis was to perform an individual patient-level prespecified pooled efficacy and safety analysis across a broad spectrum of CKD to provide more robust estimates of safety and efficacy of finerenone compared with placebo.

Methods and results: For this prespecified analysis, two phase III, multicentre, double-blind trials involving patients with CKD and type 2 diabetes, randomized 1:1 to finerenone or placebo, were combined. Main time-to-event efficacy outcomes were a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure, and a composite of kidney failure, a sustained ≥57% decrease in estimated glomerular filtration rate from baseline over ≥4 weeks, or renal death. Among 13 026 patients with a median follow-up of 3.0 years (interquartile range 2.3-3.8 years), the composite cardiovascular outcome occurred in 825 (12.7%) patients receiving finerenone and 939 (14.4%) receiving placebo [hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.78-0.95; P = 0.0018]. The composite kidney outcome occurred in 360 (5.5%) patients receiving finerenone and 465 (7.1%) receiving placebo (HR, 0.77; 95% CI, 0.67-0.88; P = 0.0002). Overall safety outcomes were generally similar between treatment arms. Hyperkalaemia leading to permanent treatment discontinuation occurred more frequently in patients receiving finerenone (1.7%) than placebo (0.6%).

Conclusion: Finerenone reduced the risk of clinically important cardiovascular and kidney outcomes vs. placebo across the spectrum of CKD in patients with type 2 diabetes.

Key question: Does finerenone, a novel selective, nonsteroidal mineralocorticoid receptor antagonist, added to maximum tolerated renin-angiotensin system inhibition reduce cardiovascular disease and kidney disease progression over a broad range of chronic kidney disease in patients with type 2 diabetes?

Key finding: In a prespecified, pooled individual-level analysis from two randomized trials, we found reductions both in cardiovascular events and kidney failure outcomes with finerenone. Because 40% of the patients had an estimated glomerular filtration rate of >60 mL/min/1.73m2 they were identified solely on the basis of albuminuria.

Take home message: Finerenone reduces the risk of clinical cardiovascular outcomes and kidney disease progression in a broad range of patients with chronic kidney disease and type 2 diabetes. Screening for albuminuria to identify at-risk patients among patients with type 2 diabetes facilitates reduction of both cardiovascular and kidney disease burden.

Keywords: Cardiorenal outcomes; Chronic kidney disease; Finerenone; Hospitalization for heart failure; Hyperkalaemia; Type 2 diabetes.

Structured Graphical Abstract

Finerenone reduced the risk of clinically important cardiovascular and kidney outcomes versus placebo across the spectrum of chronic kidney disease in patients with type 2 diabetes.

Figure 1

Time to efficacy outcomes. (A) The composite cardiovascular outcome defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure (Aalen–Johansen curve). (B) The composite kidney outcome defined as kidney failure, sustained ≥57% decrease in estimated glomerular filtration rate from baseline over ≥4 weeks, or renal death (Aalen–Johansen curve). (C) The composite kidney outcome defined as kidney failure, sustained ≥40% decrease in estimated glomerular filtration rate from baseline over ≥4 weeks, or renal death (Aalen–Johansen curve). (D) All-cause mortality (Kaplan–Meier curve). Outcomes were assessed in time-to-event analyses.

Figure 2

Efficacy outcomes. ^aStatistical tests where P-values are provided were exploratory in nature; therefore, no adjustment for multiplicity was performed. ^bThe composite of time to first onset of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure. ^cThe composite of time to first onset of kidney failure, sustained ≥57% decrease in estimated glomerular filtration rate from baseline over ≥4 weeks, or renal death. ^dInitiation of chronic dialysis for ≥90 days or kidney transplantation. ^eAnalyses for P-values not prespecified. ^fThe composite of time to first onset of kidney failure, sustained ≥40% decrease in estimated glomerular filtration rate from baseline over ≥4 weeks, or renal death. ^g  P = 1.001 to 3 decimal places.

Figure 3

Components of the composite cardiovascular outcome. Outcomes were assessed in time-to-event analyses (Aalen–Johansen curves). (A) Cardiovascular death. (B) Non-fatal myocardial infarction. (C) Non-fatal stroke. (D) Hospitalization for heart failure.