FIGARO-DKD: Finerenone CV benefit extends to wide spectrum of CKD patients with T2D
The large, phase III FIGARO-DKD trial strengthen the evidence on cardiovascular benefit (CV) of the nonsteroidal mineralocorticoid receptor (MR) antagonist finerenone, in addition to its renal benefit, across a wide spectrum of patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).
“Although previous trials have examined CV outcomes in patients with T2D and varying degrees of CKD, there remains scant evidence from dedicated clinical trials to support the use of therapies to improve cardiorenal outcomes in patients with less-advanced CKD,” said the researchers.
“This trial addressed that gap by enrolling patients with T2D without heart failure with a reduced ejection fraction [HFrEF] and with either stage 2 to 4 CKD with moderately elevated albuminuria or stage 1 or 2 CKD with severely elevated albuminuria,” they continued.
FIGARO-DKD, the second phase III trial in the finerenone clinical programme, is preceded by FIDELIO-DKD — which has demonstrated benefit in the primary kidney composite outcome whereby CKD progression was significantly delayed by 18 percent in patients with advanced CKD in T2D who were treated with finerenone.
The current trial focuses on the CV composite outcome of CV death, nonfatal stroke, nonfatal myocardial infarction (MI), or hospitalization for heart failure (HHF) as the primary endpoint. Participants were 7,437 patients (mean age 64 years, 69 percent male), whom as the investigators described, “[had] either stage 2 to 4 CKD and moderately elevated albuminuria or stage 1 or 2 CKD and severely increased albuminuria — a patient population at high CV risk that was excluded from or understudied in the FIDELIO-DKD trial.” [N Engl J Med 2021;doi:10.1056/NEJMoa2110956]
After a median 3.4 years of follow-up, finerenone significantly reduced the risk of the primary CV outcome by 13 percent compared with placebo (12.4 percent vs 14.2 percent; hazard ratio [HR], 0.87; p=0.03), with a number needed to treat of 47.
The CV benefit was primarily driven by a reduction in the component of HHF, despite the fact that patients with symptomatic HFrEF were excluded from the trial (3.2 percent vs 4.4 percent; p=0.004).
“Together, the results of FIGARO-DKD and FIDELIO-DKD suggest finerenone provides kidney and CV benefits across the spectrum of patients with CKD and T2D,” concluded lead author Dr Bertram Pitt from the University of Michigan in Ann Arbor, Michigan, US, who presented the study findings at ESC 2021.
“More than 60 percent of the patients had albuminuric CKD with an eGFR of at least 60 mL/min/1.73 m2 at baseline, which highlights the need for early CKD diagnosis with the use of urinary albumin-to-creatinine ratio [UACR] screening and for treatment to improve outcomes in this under-recognized population of patients with a high CV risk,” he explained.
“The results highlight the need for early CKD treatment to reduce the CV and HF burden in this patient population and the importance of UACR monitoring in patients with T2D and an eGFR ≥60mL/min/1.73 m2,” Pitt stressed.
“The overall incidence of treatment-emergent adverse events (TEAE) was similar between the two groups,” Pitt reported. The incidence of hyperkalaemia-related TEAE was higher with finerenone vs placebo (1.2 percent vs 0.4 percent), which according to the researchers, was a finding consistent with MR blockade.
“Because concerns about hyperkalaemia contribute to the underuse of steroidal MR antagonists in patients with HF and CKD, finerenone may be an attractive therapeutic option in these patients, with the recommended monitoring of serum potassium levels and eGFR*,” Pitt and co-authors pointed out.
*eGFR: estimated glomerular filtration rate