Mechanism of Action of Finerenone

Mechanism of Action of Finerenone

Finerenone is indicated for the treatment of adult patients with heart failure with left ventricular ejection fraction (LVEF) ≥40%, and for adult patients with chronic kidney disease associated with type 2 diabetes mellitus. As a nonsteroidal mineralocorticoid receptor antagonist (nsMRA), it has distinct pharmacological properties compared with traditional steroidal MRAs. Preclinical animal models have shown that finerenone exerts inhibitory effects in both the heart and kidney, but the clinical significance of these findings is unclear. Compared with steroidal MRAs (e.g., spironolactone, eplerenone), finerenone has no relevant affinity for androgen, progesterone, estrogen, and glucocorticoid receptors, which translates into a lower incidence of sex hormone-related adverse events. It is this ability to selectively antagonize excessive mineralocorticoid receptor activation that enables finerenone to effectively address key drivers of heart failure and chronic kidney disease, such as inflammation, fibrosis, and sodium and fluid retention.

Indications of Finerenone

Finerenone is currently approved for two indications. First, for adult patients with heart failure with LVEF ≥40% to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits. Second, for adult patients with chronic kidney disease associated with type 2 diabetes mellitus to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure. It should be noted that finerenone is not approved to reduce the risk of non-fatal stroke. These two indications cover a broad patient population and provide clinicians with important therapeutic options.

Contraindications of Finerenone

Prior to initiating finerenone, contraindications must be carefully assessed. It is contraindicated in patients with hypersensitivity to any ingredient of the product, patients receiving strong CYP3A4 inhibitors, and patients with adrenal insufficiency. The major safety risk is hyperkalemia, the risk of which increases with declining renal function and is greater in patients with higher baseline serum potassium levels. Therefore, serum potassium and eGFR must be measured in all patients before initiating treatment; if serum potassium is >5 mEq/L, treatment should not be started. Regular monitoring of serum potassium and corresponding dose adjustment are required during treatment. In addition, finerenone may cause worsening renal function in patients with heart failure, and hospitalization is required in rare cases. Initiation of treatment is not recommended in patients with heart failure who have an eGFR<25 mL/min/1.73m². Breastfeeding women should avoid breastfeeding during treatment and for 1 day after the last dose.