BACKGROUNDFinerenone, a selective nonsteroidal mineralocorticoid receptor antagonist,
has favorable effects on cardiorenal outcomes in patients with predominantly stage
3 or 4 chronic kidney disease (CKD) with severely elevated albuminuria and type 2
diabetes. The use of finerenone in patients with type 2 diabetes and a wider range
of CKD is unclear.METHODSIn this double-blind trial, we randomly assigned patients
with CKD and type 2 diabetes to receive finerenone or placebo. Eligible patients had
a urinary albumin-tocreatinine ratio (with albumin measured in milligrams and creatinine
measured in grams) of 30 to less than 300 and an estimated glomerular filtration rate
(eGFR) of 25 to 90 ml per minute per 1.73 m(2) of body-surface area (stage 2 to 4
CKD) or a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of at least
60 ml per minute per 1.73 m(2) (stage 1 or 2 CKD). Patients were treated with renin-angiotensin
system blockade that had been adjusted before randomization to the maximum dose on
the manufacturer's label that did not cause unacceptable side effects. The primary
outcome, 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 was a composite of kidney failure, a sustained
decrease from baseline of at least 40% in the eGFR, or death from renal causes. Safety
was assessed as investigator-reported adverse events.RESULTSA total of 7437 patients
underwent randomization. Among the patients included in the analysis, during a median
follow-up of 3.4 years, a primary outcome event occurred in 458 of 3686 patients (12.4%)
in the finerenone group and in 519 of 3666 (14.2%) in the placebo group (hazard ratio,
0.87; 95% confidence interval [CI], 0.76 to 0.98; P = 0.03), with the benefit driven
primarily by a lower incidence of hospitalization for heart failure (hazard ratio,
0.71; 95% CI, 0.56 to 0.90). The secondary composite outcome occurred in 350 patients
(9.5%) in the finerenone group and in 395 (10.8%) in the placebo group (hazard ratio,
0.87; 95% CI, 0.76 to 1.01). The overall frequency of adverse events did not differ
substantially between groups. The incidence of hyperkalemia-related discontinuation
of the trial regimen was higher with finerenone (1.2%) than with placebo (0.4%).CONCLUSIONSAmong
patients with type 2 diabetes and stage 2 to 4 CKD with moderately elevated albuminuria
or stage 1 or 2 CKD with severely elevated albuminuria, finerenone therapy improved
cardiovascular outcomes as compared with placebo.
