November 17, 2020
3 min read
Filippatos G, et al. LBS.07: Randomized trials — brain, kidney and heart. Presented at: American Heart Association Scientific Sessions; Nov. 13-17, 2020 (virtual meeting).
Filippatos reports he receives lecture or advisory board fees from Amgen, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Servier and Vifor. Wanner reports he receives lecture or advisory fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, FMC, Gilead, GlaxoSmithKline and MSD.
Among adults with chronic kidney disease and type 2 diabetes, the mineralocorticoid receptor inhibitor antagonist finerenone reduced the incidence of CV events regardless of CVD status, according to new data from the FIDELIO trial.
George L. Bakris
“We now have a drug, finerenone, that blocks mineralocorticoid receptor antagonist (MRA) activity that is well tolerated and safe compared with the traditional MRAs like spironolactone,” George L. Bakris, MD, professor of medicine and director of the American Heart Association-accredited Comprehensive Hypertension Center at the University of Chicago Medicine and senior author of the FIDELIO study, told Healio. “Finerenone not only slowed diabetic kidney disease progression but protected against the risk for CV events related to atherosclerosis as well as heart failure, given no interaction with the prespecified endpoint. We now have another agent in our arsenal to preserve kidney and cardiac function.”
Adults with diabetes and chronic kidney disease (CKD) have a threefold higher risk for CV death compared with those with type 2 diabetes alone, Gerasimos Filippatos, MD, FESC, FHFA, FACC, professor of cardiology at the National and Kapodistrian University of Athens in Greece, said during a press conference at the virtual American Heart Association Scientific Sessions. Overactivation of the mineralocorticoid receptor in these patients can lead to worsening CVD and kidney disease, he said.
“Finerenone has shown potent anti-inflammatory and antifibrotic effects on the cardiovascular system in animal models,” Filippatos said.
New CV analysis
As Healio previously reported, FIDELIO included 5,734 patients from 48 countries diagnosed with CKD and type 2 diabetes assigned to oral finerenone or placebo. The mean patient age in the study was 65.6 years; 70.2% were men. Mean estimated glomerular filtration rate (eGFR) was 44.3 mL/min/1.73 m2 at baseline. Almost 90% of patients had severely elevated albuminuria; nearly half the cohort (45.9%) had a history of CVD.
The primary study outcome was time to kidney failure, sustained eGFR decline of at least 40% from baseline or renal death. The key secondary outcome was time to CV death, nonfatal MI, nonfatal stroke or HF hospitalization. Data presented at American Society of Nephrology Kidney Week in October showed that finerenone was effective in reducing CV risk and slowing the progression of CKD in patients with diabetes.
During a median follow-up of 2.6 years, participants assigned finerenone were 14% less likely to experience the composite CV outcome compared with placebo (HR = 0.86; 95% CI, 0.75-0.99; P = .034). Researchers observed no significant interaction between patients with and without CVD, with an HR of 0.85 for those with a history of CVD (95% CI, 0.71–1.01) and an HR of 0.86 for those with no history of CVD (95% CI, 0.68-1.08; P = .85).
The new findings were simultaneously published in Circulation.
“Finerenone significantly reduced the overall rate of CV events by 14% compared with placebo, and we found this effect was similar in patients with a history of CVD and those without, demonstrating the benefit of finerenone for both primary and secondary CV prevention in patients with CKD and type 2 diabetes,” Filippatos said.
Investigator-reported hyperkalemia was higher among those assigned finerenone vs. placebo; however, hyperkalemia-related permanent treatment discontinuation was low compared with placebo, at 2.3% vs. 0.8% among participants with CVD and 2.2% vs. 1% among those without CVD.
The safety profile of the drug was similar among those with and without CVD, Filippatos said.
‘Learn to enroll’ the most vulnerable
The FIDELIO findings demonstrate that trialists should “learn to enroll,” and not exclude, the most vulnerable patients, including those with impaired kidney function and high CV risk, into large clinical outcome trials, Christoph Wanner, MD, from the department of medicine, division of nephrology at Würzburg University Clinic, Germany, said during a discussion after the presentation.
“The new interventions for kidney patients — SGLT2 inhibitors and MRAs — are shifting the focus away from glucose management toward organ protection,” Wanner said. “Finerenone is both a CV- and kidney-protective medication in individuals with type 2 diabetes and is an option where SGLT2 inhibitors are not preferred.”
Until the FIDELIO trial, renin-angiotensin-aldosterone system blockade therapy was limited due to rising potassium levels often seen with such therapy, Wanner said. He noted there was a “manageable” signal of hyperkalemia observed with finerenone treatment, with 18 of 100 patients showing some hyperkalemia during the trial.
“We have entered a new era of effective treatments for diabetic kidney disease — that is my feeling,” Wanner said. “Nothing has happened for 20 years. These new data shown today provide a good perspective for the FIGARO-DKD trial in 2021 to be published next year.”