Finerenone Slows CKD Progression After Heart Failure Hospitalization

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A post hoc analysis from FIDELITY shows finerenone could significantly reduce eGFR slopes among patients at risk of worsening CKD due to a heart failure hospitalization.

Finerenone Slows CKD Progression After Heart Failure Hospitalization

Tariq Shafi, MD, MHS

Credit: LinkedIn

Finerenone (Kerendia) may help reduce the decline in estimated glomerular filtration rates (eGFRs) in patients with chronic kidney disease (CKD) who have been hospitalized due to heart failure (HF).

A new post hoc subgroup analysis from the pivotal phase 3 FIDELITY trial showed that CKD progression may be further limited in patients receiving the non-steroidal mineralocorticoid receptor agonist finerenone after they had been discharged from the hospital due to HF—a specific patient population at a significantly greater risk of renal disease progression and death. The findings, presented at the National Kidney Foundation 2024 Spring Clinical Meeting (SCM) in Long Beach, CA, this week, would suggest that finerenone be considered as a post-discharge prescription in relevant patients with CKD.

Investigators from the FIDELITY trial—a combined analysis of patient-level data from the complementary phase 3 FIDELIO-DKD and FIGARO-DKD studies—conducted a post hoc analysis to explore the benefit of finerenone on CKD progression in patients recovering from hospitalization due to HF. FIDELITY initially showed in its prespecified analyses that patients with type 2 diabetes and CKD receiving the therapy had significantly reduced risk of cardiovascular and kidney disease outcomes versus placebo.

The team, led by Tariq Shafi, MD, MHS, head of the division of kidney diseases, hypertension & transplantation in the department of medicine at Houston Methodist Hospital, noted that approximately 2 in every 5 patients with type 2 diabetes will also develop CKD.

“Cardiovascular complications and CKD are closely interlinked such that progression of one can lead to the worsening of the other,” the team wrote. “Patients with CKD hospitalized for HF have greater risk of CKD progression and death. Moreover, in this patient population, higher rates of hospitalization have been observed in those with lower estimated glomerular filtration rate (eGFR) and higher urine albumin-to-creatinine ratio (UACR).”

The post hoc analysis included participants from FIDELITY who experienced a hospitalization due to HF >4 months following randomization into 1 of the 2 clinical trials. Investigators used a landmark analysis model with adjudicated hospitalization due to HF set as time 0; they then performed intention-to-treat and sensitivity on-treatment analyses at time-exclusion windows of approximately 90, 120, and 150 days.They used eGFR slopes per mL/min/1.73m2/year to interpret treatment benefit against CKD progression.

The final analysis included 239 patients receiving finerenone, versus 311 receiving placebo. Mean patient age in the finerenone arm was 66.7 years old; 62.8% were male and mean eGFR was 50.7 mL/min/1.73m2. Approximately two-thirds of patients in either treatment arm reported a history of cardiovascular disease.

In the primary analysis at the 90-day exclusion window, investigators observed a significantly slower decline in mean eGFR change from month 4 to an HF hospitalization even with finerenon (-2.8 mL/min/1.73m2/year) versus placebo (-5.4 mL/min/1.73m2/year; treatment difference, 2.7; P = .004).

Investigators additionally observed similar results at the 120-day and 150-day exclusion windows, with between-treatment eGFR slope differences of 0.37 (P = .70) and 0.71 (P = .48), respectively, between finerenone and placebo at those time periods. The between-treatment difference in eGFR slope was numerically significant from HF hospitalization through the end of the study period (1.0 mL/min/1.73m2/year).

Investigators noted the trial was limited by the use of post-baseline data at HF hospitalization to define their study subgroups. However, the findings suggest patients who experience HF hospitalization may notably reduce CKD progression with finerenone.

“Patients treated with finerenone tended to have lower eGFR decline after a hospitalization due to HF event when compared to placebo,” Shafi and colleagues wrote. “Our findings suggest that finerenone should be continued on discharge in patients experiencing a hospitalization due to HF event.”

References

Shafi T, Anker SD, Pitt B, Ruilope LM, 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.

Campbell P. FIDELITY: Finerenone Slows CKD Progression Across Full Spectrum of Severity. HCPLive. Published November 5, 2021. https://www.hcplive.com/view/fidelity-finerenone-slows-ckd-progression-across-full-spectrum-of-severity

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