Oral finerenone reduced the incidence of cardiovascular (CV) events by 14% in patients with chronic kidney disease and type 2 diabetes, regardless of whether they had a history of heart disease, results from the FIDELIO-DKD trial showed.
Over a median follow-up of 2.6 years, daily treatment of 10 mg or 20 mg with the investigational mineralocorticoid receptor antagonist cut the risk of the composite CV outcome — CV death, MI, stroke, or hospitalization for heart failure — versus placebo (HR 0.86, 95% CI 0.75-0.99, P=0.034), reported Gerasimos Filippatos, MD, of Athens University Hospital Attikon in Greece.
According to findings presented at the virtual American Heart Association (AHA) annual meeting, there also was no significant difference in the treatment effect for the composite CV outcome between patients with or without a history of CV disease (CVD; P=0.85 for interaction):
- With CVD (HR 0.85, 95% CI 0.71-1.01)
- Without CVD (HR 0.86, 95% CI 0.68-1.08)
The study was published simultaneously in Circulation.
Filippatos and co-authors also noted that the incidence of treatment-emergent adverse events was similar between treatment arms, with a low incidence of hyperkalemia-related permanent treatment discontinuation (2.3% with finerenone vs 0.8% with placebo in patients with CVD; 2.2% vs 1.0% in patients without CVD).
“We are pleased to see that finerenone could provide a meaningful treatment option for patients who are battling chronic conditions,” Filippatos said in a statement. “Treatment with finerenone significantly lowered the overall risk of cardiovascular events compared with placebo.”
AHA discussant Christoph Wanner, MD, of the University Hospital of Würzburg in Germany, called the findings “robust.”
Wanner noted that there was an increase in potassium with the study agent — the authors reported that “changes in mean serum potassium were higher with finerenone, with a maximal mean difference between the finerenone and placebo treatment groups of approximately 0.2 mEq/L in the first 4 months of treatment, with similar increases irrespective of CVD history” — but he said he did not consider it a disqualifying signal.
“The new interventions for kidney patients — SGLT2 [sodium glucose co-transporter 2] inhibitors and finerenone — are shifting the focus away from glucose management towards organ protection,” he said. “Finerenone is both a cardiovascular and kidney protective medication in individuals with type 2 diabetes, and is an option where SGLT2 inhibitors are not preferred.”
Finerenone has demonstrated the ability to reduce many of the harmful effects of mineralocorticoid receptor overactivation, which is a major driver of kidney and CV damage through inflammatory and fibrotic processes.
The phase III FIDELIO-DKD trial enrolled nearly 6,000 patients (average age 66; 70.2% male) at more than 900 sites in 48 countries. Primary results of the study were published in the New England Journal of Medicine and presented at the American Society of Nephrology’s virtual Kidney Week in October. Researchers reported there that 17.8% of the 2,833 patients on finerenone experienced a primary outcome event — kidney failure, a sustained decrease of at least 40% in estimated glomerular filtration rate from baseline, and death from renal causes — versus 21.1% of the 2,841 on placebo (HR 0.82, 95% CI 0.73-0.93, P=0.001).
For the current study, the authors explored the CV outcomes more closely. They reported that 7.7% of patients had heart failure and 45.9% had a history of CVD, including coronary artery disease, ischemic stroke, or peripheral artery disease, at baseline.
The authors also reported that there was a modest reduction in blood pressure (BP) seen with finerenone in all patients. In those with a history of CVD, systolic BP decreased 3.31 mm Hg from baseline to month 4 with finerenone versus an increase of 0.85 mm Hg with placebo. In patients without history of CVD, systolic BP dropped 3.11 mm Hg with the study drug versus a 0.53 mm Hg increase with placebo.
“The corresponding values at month 12 were -1.93 mm Hg and +1.17 mm Hg in patients with a history of CVD and -2.29 mm Hg and +0.63 mm Hg in those without a history of CVD with finerenone and placebo, respectively,” Filippatos and colleagues wrote.
Change in body weight was similar between patients in the study and placebo arms throughout the trial, the authors added.
A study limitation was that “the history of CVD was determined by review of medical records and was not formally assessed at baseline; therefore, some patients recorded without a history of CVD may have had subclinical CVD,” the researchers cautioned.
There are additional phase III trials of finerenone in progress, and Wanner pointed out that results from another finerenone trial (FIGARO-DKD) are scheduled for release in 2021.
Last Updated November 18, 2020
FIDELIO-DKD was funded by Bayer AG. Several co-authors are company employees.
Filippatos disclosed relevant relationships with Boehringer-Ingelheim, Vifor, Bayer, Novartis, Medtronic, Servier, and Amgen.
Wanner disclosed relevant relationships with AstraZeneca, Bayer, Boehringer-Ingelheim, FMC, Gilead, GlaxoSmithKline, Lilly, and MSD.