Spironolactone and eplerenone improve outcomes in heart failure. Finerenone is the newest mineralocorticoid receptor antagonist and is being tested for treatment of chronic kidney disease in people with type 2 diabetes i.e. to slow progression of kidney disease. There is potential for a huge market here despite the efficacy of ACE inhibitors and angiotensin-receptor blockers because diabetic kidney disease remains common and problematic.
FIDELIO-DKD reported its results in 2020 in the New England Journal of Medicine. FIDELIO-DKD was a double-blind randomised controlled trial of finerenone versus placebo in people with type 2 diabetes and chronic kidney disease defined by eGFR and albuminuria thresholds. There was a reduction in the risk of the primary outcome with finerenone compared to placebo. That primary outcome was a composite of kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes.
Bayer issued a press release for partner trial, FIGARO-DKD, which is due to report its results this year, 2021. This double-blind randomised trial of finerenone versus placebo looked at the same patient population (diabetes with chronic kidney disease – although more patients had earlier stage kidney disease than in FIDELIO-DKD) but had a different primary outcome: a composite of cardiovascular death, myocardial infarction, stroke and heart failure hospitalization. There was a reduction in these cardiovascular outcomes with finerenone compared to placebo.
Of course, we will need to see the full published paper but these are very promising findings. It is expected that the main results of FIGARO-DKD, and also the results of the planned pooled analysis of FIDELIO-DKD and FIGARO-DKD, will be presented at the ESC congress early in September, this year.
We will have an eye on the rate of hyperkalemia, since this non-steroidal mineralocorticoid receptor antagonist is described as being potentially more “kidney-friendly”, which it seems to be, given the kidney benefits in FIDELIO-DKD. So far, Spironolactone and Eplerenone, are not recommended in patients with low eGFR. However, after an initial push back from nephrologists, spironolactone is now being tested in even more severe, end-stage kidney disease (ALCHEMIST, ACHIEVE).
It is likely that there will be discussions about a “class effect”. However a class effect, at least for the time being, is not very relevant, since Finerenone and Spironolactone/Eplerenone are intended for different patient populations (diabetic kidney disease versus heart failure/ post-myocardial infarction. Nevertheless, Finerenone is also now being investigated in heart failure with preserved ejection fraction (FINEARTS). Hold your breath! Mineralocorticoid receptor antagonists are here to stay!