Finerenone, in patients with mild-to-moderate renal disease and T2D, reduced CV event risk by 13% and risk for a composite renal event by 23%, study authors reported at ESC 2021.
Finerenone, a first-in-class nonsteroidal mineralocorticoid receptor antagonist, reduces risk of cardiovascular (CV) morbidity and mortality in adults with mild-to-moderate kidney disease and type 2 diabetes (T2D). The finding, from the FIGARO-DKD trial, was reported on August 28 at the European Society of Cardiology (ESC) Congress 2021.
Specifically, finerenone reduced CV event risk by 13% for adults with diabetic kidney disease vs placebo, primarily driven by a 29% reduction in hospitalization for heart failure.
The FIGARO-DKD results follow closely the recent approval of finerenone (Kerendia) by the US Food and Drug Administration to slow progression of kidney disease and reduce risk of cardiovascular events in patients with advanced (stage 3-4) chronic kidney disease (CKD) and T2D. Approval was based on results of the landmark FIDELIO-DKD study which enrolled participants with more significant renal impairment than those recruited for FIGARO-DKD. Taken together the combined results suggest a role for finerenone to treat patients along a continuum of reduced kidney function.
“Finerenone improved cardiovascular outcomes in patients with mild-to-moderate kidney disease and type 2 diabetes treated with optimized RAS blockade and with well-controlled blood pressure and diabetes,” said principal investigator Bertram Pitt, MD, professor of medicine emeritus at the University of Michigan School of Medicine, in a ESC statement.
“The benefits of finerenone were consistent across eGFR and urine albumin-to-creatinine ratio (UACR) categories. Together with FIDELIO-DKD, the results support the use of finerenone to improve cardiorenal outcomes across the spectrum of kidney disease and type 2 diabetes.”
The randomized double-blind FIGARO-DKD trial enrolled >7000 adults with T2D from 48 countries who were assigned to receive finerenone or placebo. Eligibility requirements were urinary albumin-to-creatinine ratio (UACR) of 30 to <300 and estimated glomerular filtration rate (eGFR) of 25 - 90 ml/min/1.73 m2 (stage 2 to 4 CKD) or UACR of 300 - 5000 and eGFR of at least 60 ml/min/1.73 m2 (stage 1 or 2 CKD). For all participants, renin-angiotensin blockade was adjusted before randomization to maximum labeled dose.
The primary outcome, which was assessed in a time-to-event analysis, was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The first secondary outcome of interest was a composite of kidney failure, a sustained decrease from baseline of at least 40% in eGFR, or death from renal causes.
The final analyses included 7437 patients—3686 randomized to finerenone and 3666 to placebo. Mean age across participants was 64.1±9.8 years; 69.4% were men; mean eGFR was 67.8±21.7 ml/min/1.73m2, and 45.3% had a history of cardiovascular disease.
During follow-up (median 3.4 years), a primary outcome event had occurred among 12.4% (n=458) receiving finerenone and 14.2% (n=519) receiving placebo (hazard ratio [HR], 0.87 [95% confidence interval [CI], 0.76-0.98]; P=.03). Investigators report the benefit was driven primarily by a 29% lower incidence of hospitalization for heart failure (HR, 0.71; 95% CI, 0.56-0.90).
The secondary composite outcome (kidney failure, a sustained decrease from baseline of at least 40% in the eGFR, or death from renal causes) was observed in 9.5% (n=350) of patients receiving finerenone and 10.8% (n=395) of patients in the placebo group (HR, 0.87; 95% CI, 0.76-1.01; p=0.07).
Other secondary outcomes
A composite of kidney failure, sustained decrease in eGFR ≥57% from baseline, or renal death occurred in 108 (2.9%) and 139 (3.8%) patients in the finerenone and placebo groups, respectively (HR 0.77; 95% CI 0.60–0.99).
ESRD occurred in 32 (0.9%) and 49 (1.3%) patients in the finerenone and placebo groups, respectively (HR 0.64; 95% CI 0.41–<1.00).
Safety analysis, according to the study, found no substantial difference in overall frequency of adverse events between finerenone and placebo groups. Hyperkaliemia, authors report, was increased with finerenone (10.8%) compared to placebo (5.3%), but subsequent discontinuation of study drug was low (1.2% with finerenone versus 0.4% with placebo).
Abstract presented at ESC Congress 2021: FIGARO-DKD: finerenone in patients with chronic kidney disease and type 2 diabetes
Reference: Bertram Pitt B, Filippatos G, Agarwal R, et al for the FIGARO-DKD Investigators. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. Published online August 28, 2021. DOI: 10.1056/NEJMoa21109569