Nonsteroidal MRAs ‘save lives’ in diabetes with cardiorenal disease
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PHILADELPHIA — For adults with type 2 diabetes and chronic kidney disease, a novel nonsteroidal mineralocorticoid receptor antagonist can play a key role in reducing risk for serious cardiorenal outcomes, according to a speaker.
The FDA approval of the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia, Bayer) for reducing risks for kidney and heart complications for adults with CKD associated with type 2 diabetes has ushered in a new era of “triple therapy” for diabetic kidney disease and, potentially, people with nondiabetic kidney disease, according to Robert Toto, MD, the Mary M. Conroy Professor of Kidney Disease and assistant dean of translational science at UT Southwestern Medical Center. Steroidal MRAs, such as spironolactone and eplerenone, also play a role in the management of people with diabetes and heart failure, Toto said while speaking at the Heart in Diabetes CME conference.
“Mineralocorticoid receptor antagonists save lives in those with cardiorenal diseases in the setting of diabetes,” Toto told Healio. “There is a broad spectrum of efficacy and safety of nonsteroidal MRAs among those with diabetes and chronic kidney disease.”
Evidence of benefit clear
Toto said that, overall, “it is clear” that steroidal MRAs improve survival in people with heart failure with reduced ejection fraction (HFrEF); new evidence now shows the benefit of finerenone in diabetic kidney disease.
“What is unique about finerenone is it does not penetrate the central nervous system; it has high selectivity for the MRA receptor and has a relatively short half-life vs. spironolactone, which has a very long half-life,” Toto said.
Toto highlighted findings from the FIDELIO-DKD, FIGARO-DKD and FIDELITY trials, demonstrating significant risk reduction for both the cardiovascular composite and kidney outcomes with finerenone compared with placebo. In FIDELTY, a prespecified pooled analysis of the FIDELIO and FIGARO trials, risk for CV morbidity and mortality was reduced by 14% vs. placebo and the risk for CKD progression was reduced by 23% vs. placebo.
The incidence of hyperkalemia in the finerenone trials was low; however, monitoring of serum potassium remains important, Toto said.
“In both of the FIGARO and FIDELITY studies, cases with HFrEF were excluded, because guidelines already recommend those patients be prescribed a steroidal MRA,” Toto said.
Measure albumin, GFR
“Finerenone is an emerging new drug, approved by the FDA for patients with diabetic kidney disease and albuminuria,” Toto said. “It is important to measure the albumin to detect patients at risk for progression to CKD. Measuring the [glomerular filtration rate] is also important because the starting dose [of finerenone] will vary depending on what that GFR is. If between 25 mL/min/1.73 m2 to 60 mL/min/1.73 m2, for example, it is recommended you start with 10 mg instead of 20 mg.”
With the approval of finerenone, triple therapy for reducing risk for a first CV or renal outcome is now recommended for people with type 2 diabetes and CKD, Toto said. This includes use of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker, nonsteroidal MRA and an SGLT2 inhibitor.
“We are starting to see use of this ‘triad’ increase,” Toto said. “Guidelines from KDIGO state that nonsteroidal MRAs are most appropriate for people with type 2 diabetes at high risk for progression to CV or renal events.”
For people with heart failure, beta-blockers, ACE inhibitors or an angiotensin receptor/neprilysin inhibitor, a steroidal MRA and an SGLT2 inhibitor are recommended, Toto said.
“In patients with HFrEF, MRAs like spironolactone or eplerenone are important for reducing morbidity and mortality,” Toto said. “We now have these pillars, with nephrology borrowing a bit from cardiology. We will begin to see greater use of nonsteroidal MRAs, at least in the kidney disease population.”
Ongoing trials
Despite compelling data for nonsteroidal MRAs, Toto said more research is needed in different populations.
“Research is needed in nondiabetic populations with chronic kidney disease, and studies of combinations of nonsteroidal MRAs with SGLT2 inhibitors and GLP-1 receptor agonists in diabetic kidney disease,” Toto told Healio.
There are currently ongoing trials of MRAs in both heart failure and CKD, Toto said. Two studies, SPIRIT-HF and SPIRRIT, are each assessing the use of spironolactone on CV death and total heart failure hospitalizations in people with heart failure with an ejection fraction greater than 40%. In the ongoing FINEARTS-HF study, researchers are assessing the use of finerenone on CV death and total heart failure events in 5,500 adults with heart failure with midrange ejection fraction. In the FIND-CKD study, researchers are assessing the effect of finerenone vs. placebo on change in eGFR slope in participants with nondiabetic CKD.
Other studies will look at combination therapy. In the MIRACLE study, researchers will assess the effect of a combined SGLT2 inhibitor (dapagliflozin [Farxiga, AstraZeneca]) plus an MRA in 500 adults with heart failure and CKD. The CONFIDENCE study will also assess a combination of an SGLT2 inhibitor, empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly), plus finerenone compared with each treatment alone in more than 800 participants with long-term CKD and type 2 diabetes, Toto said.
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Toto R. Session 3: State of the Art Cardio-Renal-Metabolic Diseases. Presented at: Heart in Diabetes; June 24-26, 2022; Philadelphia (hybrid meeting).
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