For patients with diabetic kidney disease, finerenone, an agent from a new class of selective, nonsteroidal mineralocorticoid receptor antagonists, led to significant reductions in combined adverse renal outcomes and in combined adverse cardiovascular outcomes in the pivotal.
And the safety results showed a good level of tolerability. The rate ofwas higher with finerenone than with placebo, but the rate of drug discontinuations for elevated potassium was lower than that seen with , a steroidal mineralocorticoid receptor antagonist (MRA).
“An ideal drug would cause no hyperkalemia, but the absolute risk we saw is a fraction of what we see with spironolactone in this vulnerable patient population,” said Rajiv Agarwal, MD, from Indiana in Indianapolis, during a press briefing.
After a median follow-up of 2.6 years, finerenone was associated with a 3.4% absolute reduction in the rate of combined adverse renal events, the study’s primary end point, which comprised kidney failure, renal death, and a drop in estimated glomerular filtration rate (eGFR) of at least 40% from baseline. This produced a significant relative risk reduction of 18%, with a number needed to treat of 32 to prevent one of these events, Dr. Agarwal reported at Kidney Week 2020. Findings from the FIDELIO-DKD trial weresimultaneously in the New England Journal of Medicine.
Finerenone was also associated with an absolute 2.4% reduction in the rate of combined adverse cardiovascular events, the study’s “key secondary end point,” which included cardiovascular death, nonfatal MI, nonfatal, and hospitalization for . This translated into a significant relative risk reduction of 14% and a number needed to treat of 42 to prevent one of these events.
FIDELIO-DKD assessed 5,734 patients with type 2 diabetes and
A suggestion of less severe hyperkalemia
Finerenone was well tolerated by the participants, and the findings suggest that it caused less clinically meaningful hyperkalemia than spironolactone, the most established and widely used MRA.
Like all MRA drugs, finerenone led to an increase in serum potassium in all patient subgroups – in this case 0.2 mmol/L – unlike placebo, said Dr. Agarwal.
The overall incidence of hyperkalemia was 16% in the 2,827 evaluable patients in the finerenone group and 8% in the 2,831 evaluable patients in the placebo group. Fewer than 10% of patients in the trial received a potassium-binding agent.
The rate of hyperkalemia leading to treatment discontinuation was higher in the finerenone group than in the placebo group (2.3% vs. 0.9%).
That 2.3% rate is 10 times lower than the 23.0% rate of hyperkalemia-related treatment discontinuation in patients who received spironolactone and no potassium-binding agent, said Dr. Agarwal, citing ahe was involved with.
He hypothesized that finerenone might cause less clinically meaningful hyperkalemia because it creates no active metabolites that linger in the body, whereas spironolactone produces active metabolites with a half life of about 1 week.
“The risk for hyperkalemia is clearly increased with finerenone compared with placebo, and in the absence of head-to-head studies, it’s hard to know how it compares with spironolactone or[Inspra],” the other agents in the MRA class, said Mikhail N. Kosiborod, MD, from the University of Missouri–Kansas City.
“The rates of hyperkalemia observed in FIDELIO-DKD were overall comparable to what we would expect from eplerenone. But the rate of serious hyperkalemia was quite low with finerenone, which is reassuring,” Dr. Kosiborod said in an interview.
And the adverse-effect profile showed that finerenone “is as safe as you could expect from an MRA,” said Janani Rangaswami, MD, from the Einstein Medical Center in Philadelphia.
The rate of hyperkalemia should be interpreted in the context of the high risk the enrolled patients faced, given that they all had moderate to severe diabetic kidney disease with albuminuria and, in some cases, eGFR rates as low as 25 mL/min per 1.73m2, she explained. In addition, all patients were on maximally tolerated treatment with either an angiotensin-converting–enzyme inhibitor or an angiotensin receptor blocker to inhibit the renin angiotensin system (RAS).
“Considering this background, it’s a very acceptable adverse-event profile,” Dr. Rangaswami said in an interview.