Finerenone Treatment Slows Chronic Kidney Disease Progression After Heart Failure Hospitalization

Results from a post hoc subgroup analysis of the FIDELITY study revealed patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) treated with finerenone had slower CKD progression—as measured by estimated glomerular filtration rate (eGFR)—after being hospitalized for heart failure, according to a poster presented at the National Kidney Foundation (NKF) 2024 Spring Clinical Meeting.¹ Investigators believe these findings encourage continued treatment with the drug after hospitalization discharge.

“CKD is a common complication of T2D, affecting approximately 40% of patients with T2D,” wrote a team of international investigators led by Tariq Shafi, MD, MHS, head of the Division of Kidney Diseases, Hypertension, & Transplantation and Jerold B. Katz Investigator at the Houston Methodist Hospital. “Cardiovascular complications and CKD are closely interlinked such that progression of one can lead to the worsening of the other.”

The FIDELITY study was a prespecified pooled analysis of the complementary phase 2 clinical trials, FIDELIO-DKD and FIGARO-DKD, in which treatment with finerenone was shown to better reduce the risk of both cardiovascular and kidney outcomes in patients with CKD and T2D when compared with placebo. The post hoc analysis presented at the conference evaluated the benefits of continuing treatment within this population after being hospitalized for heart failure.

Patients receiving optimized renin–angiotensin system blockade were randomized to either finerenone or placebo. This patient population included those who experienced hospitalization for heart failure > 4 months post-randomization and used a landmark analysis model with adjudicated hospitalization for heart failure set as time 0. Eligible patients were aged ≥ 18 years, were diagnosed with T2D, were receiving a maximum tolerated dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for ≥ 4 weeks, and exhibited moderately or severely increased albuminuria.

The intention-to-treat and sensitivity on-treatment analyses were conducted using time-exclusion windows of ±90, ±120 and ±150 days of hospitalization for heart failure. The changes in eGFR slopes were determined by mixed effects models. eGFR slopes from month 4 to hospitalization for heart failure, as well as from hospitalization to the end of the study, were reported as least-squares mean changes in eGFR.

At baseline, patient characteristics were generally balanced among those receiving finerenone (n = 239) and placebo (n = 311). In the finerenone group, 62.8% were male, the mean age was 66.7 years, and the mean duration of diabetes was 18.0 years. In the placebo group, 74.9% were male, the mean age was 67.8 years, and the mean duration of diabetes was 17.6 years.

In the primary analysis, patients receiving finerenone exhibited a slower progression in CKD before being hospitalized for heart failure when compared with placebo (-2.8 ml/min/1.73 m²/year vs -5.4 ml/min/1.73 m²/year, respectively). A numerically slower decline in eGFR was reported in the finerenone cohort after hospitalization when compared with placebo (between-treatment difference of 1.0 ml/min/1.73 m²/year, P = .34). Findings were similar for other time-exclusion windows and sensitivity analyses.

Investigators noted the benefits of the randomization process were invalidated by the use of the post-baseline data used to define the subgroups. Therefore, there is a potential for unmeasured confounding with the possible imbalances in the randomized groups that could have biased efficacy outcome data.

However, the analysis was strengthened by using data from an international, multicenter, diverse cohort of patients, which in turn increased the generalizability of the findings. Further, the hospitalization for heart failure events were independently adjudicated to confirm both the accuracy and consistency of these events. Lastly, the serum creatinine was routinely measured per research protocol, so findings were not confounded by indication.

References

1. ^{Shafi T, Anker SD, Pitt B, Ruilope L, et al. Effectiveness of finerenone in slowing CKD progression after hospitalization for heart failure: A FIDELITY subgroup analysis. Poster presented at: National Kidney Foundation 2024 Spring Clinical Meeting (SCM). Long Beach, CA. May 14 – 18, 2024.}