‘Consistent’ benefits irrespective of SGLT2 inhibitors
“The cardiovascular and kidney benefits of finerenone were consistent irrespective of SGLT2 inhibitor use. This is definitely interesting and warrants a randomized controlled trial” to examine the relationship in a more rigorous way, commented Tejas Desai, MD, a nephrologist with the Department of Veterans Affairs, Charlotte, N.C.
That study, CONFIDENCE, is on its way, Dr. Rossing said during his talk. The randomized phase 2 trial has a planned enrollment of 800 patients with type 2 diabetes and CKD and three treatment groups: finerenone plus placebo, the SGLT2 inhibitor empagliflozin (Jardiance) plus placebo, or finerenone plus empagliflozin. The study will launch later in 2022 and has a planned completion date of late 2023.
“SGLT2 inhibitors, compared with finerenone, is where all of this is headed. We need a large trial that adjudicates the best medication to use with a RAS inhibitor,” Dr. Desai said in an interview.
The new analyses from the combined FIDELITY study expand on a previous report presented at the 2021 annual congress of the European Society of Cardiology and published in the European Heart Journal.
‘Impressive’ effect on cardiovascular events
The main findings from FIDELITY presented in those earlier reports, in 13,026 patients, showed there was a significant 14% relative reduction in the composite cardiovascular endpoint with finerenone, compared with placebo, during a median 3 years of follow-up.
The same report documented, in the total combined cohort, a significant 23% relative reduction in the composite renal endpoint in those taking finerenone compared with placebo.
“Reducing the risk of cardiovascular endpoints by a relative 14% is impressive,” and the time course showed a “relatively quick onset of action,” Dr. Desai noted.
He also characterized the enrolled patients, which included many with stage 3 or 4 CKD, as “not the sickest population of patients with CKD,” but rather “relatively healthier patients with CKD.”
Dr. Desai also downplayed the importance of the observed reduction in UACR associated with finerenone in FIDELITY.
“UACR is a surrogate marker. Results from many studies have shown improvements in UACR only to not show protection against falls in eGFR rate,” Dr. Desai said.
He was also reassured by the low incidence of hyperkalemia that led to discontinuation, which occurred in 1.7% of patients taking finerenone and in 0.6% of those taking placebo.
The types of patients enrolled in FIDELIO-DKD and FIGARO-DKD, who did not have eGFR rates below 25 mL/min per 1.73 m2, are not particularly susceptible to this adverse effect, he said, noting, “I’m not overly concerned with hyperkalemia in this CKD population.
“I’m more concerned about [hyperkalemia in] patients with CKD and an eGFR of less than 25 mL/min per 1.73 m2, but this was less than 1% of the enrolled population,” Dr. Desai observed.
FIDELIO-DKD, FIGARO-DKD, and FIDELITY were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Rossing reported being a consultant for Bayer and other drug companies, and receiving research funding from AstraZeneca and Novo Nordisk. Dr. Desai reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.