FIDELIO-DKD: Finerenone offers new treatment option for diabetic CKD
medwireNews: The selective mineralocorticoid receptor antagonist finerenone significantly reduces the risk for progression of chronic kidney disease (CKD) and for cardiovascular events in people with type 2 diabetes, show the FIDELIO-DKD findings.
“The observed benefits of finerenone were clinically significant and were obtained on a background of guideline-directed therapy, including RAS [renin-angiotensin system] blockade at a maximum labeled dose that did not cause unacceptable side effects plus well-controlled glycated hemoglobin and blood pressure levels,” write the investigators in The New England Journal of Medicine.
The trial’s primary endpoint was a composite of kidney failure, a sustained reduction of at least 40% in estimated glomerular filtration rate (eGFR) from baseline, or death from renal causes. During a median follow-up of 2.6 years, this occurred in 17.8% of the 2833 study participants taking daily finerenone versus 21.1% of the 2841 taking placebo, giving a significant 18% risk reduction with finerenone.
George Bakris (University of Chicago, Illinois, USA) and co-investigators note this effect is not as great as was achieved with canagliflozin in the CREDENCE trial. However, they point out that participants in FIDELIO-DKD were allowed to take sodium-glucose cotransporter 2 inhibitors, including canagliflozin, whereas CREDENCE excluded patients treated with mineralocorticoid receptor antagonists.
Finerenone treatment also significantly reduced the risk for the key secondary composite cardiovascular outcome, comprising nonfatal myocardial infarction, nonfatal stroke, cardiovascular mortality, and hospitalization for heart failure. This occurred in 13.0% of the group, compared with 14.8% of those taking placebo, giving a 14% risk reduction.
With the exception of stroke, the risk for all individual endpoints was lower with finerenone than placebo, albeit not always significantly so.
Finerenone was given at a dose of 10 or 20 mg/day according to current eGFR and serum potassium levels, and could be suspended if potassium exceeded 5.5 mmol/L.
The researchers say that previous trials in which patients with diabetic kidney disease received two drugs targeting the RAS had not only poor efficacy, but also increased risk, particularly for acute kidney injury, hypotension, and hyperkalemia.
“[S]uch adverse events may be due to the inhibition of two proximal targets in the RAS cascade,” they suggest.
In this trial of RAS blockade plus a mineralocorticoid receptor antagonist, adverse events and serious adverse events occurred at a similar rate in both treatment groups, as did rates of acute kidney injury, at 4.6% and 4.8% in the finerenone and placebo groups, respectively.
Hyperkalemia was more frequent in the finerenone than the placebo group, at a rate of 18.3% versus 9.0%, but only 2.3% of the finerenone group discontinue therapy due to hyperkalemia, which the team says is “markedly lower” than the discontinuation rate in trials of dual RAS blockade.
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