FIGARO-DKD: Finerenone cardioprotective across broad range of renal risk
medwireNews: Finerenone protects against adverse cardiovascular outcomes in people with type 2 diabetes and mild or moderate chronic kidney disease (CKD), the FIGARO-DKD investigators have reported at the virtual ESC Congress 2021.
The previously published FIDELIO-DKD trial showed that the nonsteroidal mineralocorticoid receptor antagonist significantly reduced the risk for progression of kidney disease (the primary endpoint) and for a composite cardiovascular outcome (a key secondary outcome) in people at very high risk for renal events.
The 7352 FIGARO-DKD participants had less severe kidney disease, but were nevertheless at high cardiovascular risk; they had either a moderately elevated albumin to creatinine ratio (30 to <300) and stage 2–4 CKD or a severely elevated ratio (300–5000) and stage 1 or 2 CKD.
“Together, these two trials included a spectrum of CKD in type 2 diabetes — patients with stage 2 to 4 CKD with moderately elevated albuminuria or with stage 1 to 4 CKD with severely elevated albuminuria,” write Bertram Pitt (University of Michigan School of Medicine, Ann Arbor, USA) and co-researchers in the concurrently published paper in The New England Journal of Medicine.
They add that “there remains scant evidence from dedicated clinical trials to support the use of therapies to improve cardiorenal outcomes in patients with less-advanced CKD.”
During a median follow-up of 3.4 years, 12.4% of people randomly assigned to take finerenone at a target dose of 20 mg/day had a primary outcome event (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure).
This represented a significant 13% relative reduction on the rate in people given placebo, which was 14.2%, and equated to a number needed to treat of 47 to prevent one outcome event. The researchers stress that this improvement was obtained “on a background of guideline-directed therapy” for kidney disease, plus frequent use of cardiovascular and diabetes medications.
The positive effect on the primary outcome was driven by a 29% reduction in the risk for heart failure hospitalization, with rates being 3.2% versus 4.4% in the finerenone and placebo groups, respectively.
This was “despite the exclusion of patients who had symptomatic heart failure with a reduced ejection fraction” from the trial, say the study authors.
Participants’ risk for the key composite renal outcome of kidney failure, a sustained estimated glomerular filtration rate decrease of at least 40%, or renal death was not significantly altered by finerenone treatment. The rate was 9.5%, compared with 10.8% in the placebo group, giving a nonsignificant 13% relative reduction.
However, speaking during a press conference, Pitt noted that the 40% eGFR reduction was selected with regulatory considerations in mind. He reported that when using “the more stable and sensitive” 57% threshold, as used in “most of the other renal trials,” finerenone treatment was associated with a significant 23% reduction in risk for the combined renal endpoint, at a rate of 2.9% versus 3.8% with placebo.
Hyperkalemia was more common with finerenone than placebo treatment, at 6.5% versus 3.1%, with a corresponding 1.2% versus 0.4% stopping treatment because of the complication.
But Pitt stressed how low this rate is compared with existing renal medications. “You will never see that in this kind of a renal population with the steroidal MRAs,” he said. “So this drug is really efficacious and well tolerated.”
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