Finerenone reduces CV events, renal outcomes in T2D-related CKD

A pooled analysis of 13,171 patients from both the FIDELIO-DKD and FIGARO-DKD trials has confirmed the beneficial effects of finerenone, according to results of FIDELITY study, presented at the recently concluded American College of Cardiology Annual Scientific Session (ACC 2022).

The composite outcomes of cardiovascular (CV) death, myocardial infarction (MI), stroke, and hospitalization for heart failure (HHF) were lower with finerenone compared with placebo (12.7 percent vs 14.4 percent; HR, 0.86, 95 percent CI, 0.78‒0.95; p=0.0018). [Eur Heart J 2022;43:474-484]

Time to kidney failure, sustained ≥57-percent decrease in eGFR from baseline, or renal death was also significantly reduced with finerenone (5.5 percent vs 7.1 percent; HR, 0.77, 95 percent CI, 0.67‒0.88; p=0.0002), as were all-cause mortality (8.5 percent vs 9.4 percent; p=0.051) and all-cause hospitalization (43.5 percent vs 45 percent; p=0.087) relative to placebo.

In addition, FIDELITY confirmed the beneficial effects of finerenone on CV and renal outcomes regardless of baseline atherosclerotic cardiovascular disease history. Notably, patients with symptomatic heart failure with reduced ejection fraction (HFrEF) were excluded from the trials.

FIDELIO

Previously use of finerenone led to favourable CV and renal outcomes among patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) receiving maximal renin-angiotensin system therapy, results of the FIDELIO-DKD trials showed.

Finerenone also reduced the incidence of atrial fibrillation (AF) or flutter (AFL) but increased the risk of hyperkalaemia in this patient population.

“This is hypothesis generating and will likely need to be further validated,” Dharam J. Kumbhani, MD, of the ACC said, noting a similar benefit with eplerenone but not with spironolactone (different patient populations, but all of them are mineralocorticoid receptor antagonists [MRAs]).

A total of 13,911 patients (mean age 66 years, 30 percent female) were screened, but only eligible patients were randomized to receive finerenone (n=5,292) or placebo (n=5,292). Those with HFrEF and New York Heart Association class II-IV, uncontrolled hypertension, glycated haemoglobin >12 percent, and other kidney disease were excluded.

Patients with an estimated glomerular filtration rate (eGFR) between 25 and 60 ml/min/1.73 m² at the screening visit received an initial dose of 10 mg once daily, while those with an eGFR ≥60 ml/min/1.73 m² received an initial dose of 20 mg once daily. After 1 month, dose was increased from 10 to 20 mg once daily if the serum potassium level was ≤4.8 mmol/L and the eGFR was stable.

The composite outcome of kidney failure, sustained decrease of 40 percent in the eGFR from baseline, or death from renal causes occurred less frequently among patients in the finerenone group compared with those in the placebo group (17.8 percent vs 21.1 percent; hazard ratio [HR], 0.82, 95 percent confidence interval [CI], 0.73‒0.93; p=0.0014).

Likewise, treatment with finerenone resulted in more favourable secondary outcomes, except for hyperkalaemia (15.8 percent vs 7.8 percent), relative to placebo: CV death, MI, stroke and HHF (13 percent vs 14.8 percent; p=0.03), CV death (4.5 percent vs 5.3 percent; p>0.05), nonfatal MI (2.5 percent vs 3.1 percent), and HHF (4.9 percent vs 5.7 percent).

The rate of new-onset AF or AFL over 2.6 years was also lesser for finerenone compared with placebo (3.2 percent vs 4.5 percent; HR, 0.71, 95 percent CI, 0.53‒0.94; p=0.016). Baseline AF/AFL was present in 8.1 percent of patients. No between-group difference was seen for primary or key secondary renal or CV outcomes based on AF/AFL history, but CV events were higher among patients with AF/AFL compared to those without.

“Finerenone is a novel, nonsteroidal, selective MRA with anti-inflammatory and antifibrotic effects,” the researchers said. “It is thought to have higher potency and less hyperkalaemia than steroidal MRAs such as spironolactone and eplerenone.”