Finarone reduces CV and kidney outcomes in diabetics with CKD: Fidelity

A recent study suggests that finerenone reduced the risk of cardiovascular and kidney outcomes in patients with chronic kidney disease and type 2 diabetes, irrespective of patient history of cardiovascular disease.

The study findings were presented at the American College of Cardiology 2022 Scientific Sessions on April 04, 2022.

Despite recommended treatment, the risk of CKD progression remains and newer therapies are needed. Therefore, Dr Gerasimos S. Filippatos and his team conducted a study to assess the safety and efficacy of finerenone in reducing cardiovascular (CV) events among patients with type 2 diabetes mellitus (T2DM) and CKD.

Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist (MRA) with anti-inflammatory and antifibrotic effects. It is felt to have higher potency and less hyperkalemia than steroidal MRAs such as spironolactone and eplerenone.

In this prespecified pooled analysis of FIDELIO-DKD and FIGARO-DKD, the researchers included 7352 patients and randomized them to either finerenone (n = 3,686) or placebo (n = 3,666). Patients with an estimated glomerular filtration rate (eGFR) of 25-60 ml/min/1.73 m2 at the screening visit received an initial dose of 10 mg once daily, and those with an eGFR of ≥60 at the screening visit received an initial dose of 20 mg once daily. The researchers further escalated the dose from 10 to 20 mg once daily after 1 month, provided the serum potassium level was ≤4.8 mmol/L and the eGFR was stable. The primary outcome assessed was the incidence of CV death, myocardial infarction (MI), stroke, hospitalization for HF, for finerenone vs. Placebo. The key secondary composite outcome, assessed were incidence of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure, End-stage kidney disease (ESKD).

Key findings of the study:

• Upon analysis, the researchers found that the primary outcome occurred in 12.4% of patients in the finerenone group and 14.2% of patients in the placebo group (hazard ratio [HR] 0.87).

· CV death: 5.3% vs. 5.8%

· MI: 2.8% vs 2.8%

· Stroke: 2.9% vs 3.0%

· Hospitalization for HF: 3.2% vs 4.4%

• The secondary outcomes for finerenone vs placebo were:

· Kidney failure (sustained decrease from baseline of ≥40% in GFR, or death from renal cause): 9.5% vs 10.8% (HR 0.87)

· End-stage kidney disease (ESKD): 0.9% vs 1.3% (HR 0.64)

· All-cause hospitalizations: 42.7% vs 43.8%

· All-cause mortality: 9% vs 10.1% (HR 0.89)

· Hyperkalemia: 10.8% vs 5.3%

• They noted that the finerenone has salutary effects on CV outcomes among patients with T2DM and CKD who were on a background of maximal RAS blockade therapy, primarily due to a reduction in hospitalization for HF.
• They further highlighted that there was also a reduction in ESKD.
• They observed that new-onset HF was reduced among patients without HF at baseline. However, there was a higher risk of hyperkalemia with finerenone.
• Upon pooled FIDELITY analysis, the confirmed a benefit in CV and renal outcomes with finerenone, irrespective of baseline atherosclerotic cardiovascular disease (ASCVD) history.

"The safety profile of finerenone was similar between patients with and without a history of atherosclerotic cardiovascular disease. Although hyperkalemia was increased with finerenone, the clinical impact was minimal. Finerenone has shown benefit in primary and secondary prevention across the spectrum of patients with chronic kidney disease and type 2 diabetes with a good safety profile." said the study authors in their presentation.

For further information:

Presented by Dr. Gerasimos S. Filippatos at the American College of Cardiology Annual Scientific Session (ACC 2022), Washington, DC, April 4, 2022.

Keywords:

Finerenone, chronic kidney disease, type 2 diabetes, mineralocorticoid receptor antagonist, FIDELIO-DKD, FIGARO-DKD, estimated glomerular filtration , CV death, myocardial infarction, stroke, Heart Failure, ACC 2022 Scientific Sessions.