Cardiovascular Effects of Finerenone

Cardiovascular Effects of Finerenone

Two large Phase III trials were conducted with finerenone in patients with chronic kidney disease and type 2 diabetes mellitus: FIGARO-DKD (N=7352, median follow-up 3.4 years) and FIDELIO-DKD (N=5674, median follow-up 2.6 years). FIGARO-DKD primarily evaluated cardiovascular outcomes; its primary composite endpoint (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure) showed that finerenone reduced the absolute risk by 2.1% with a number needed to treat of 47. Among these, the reduction in risk of hospitalization for heart failure was most pronounced (relative risk reduction 29%), and there was a trend toward a reduction in cardiovascular death (relative risk reduction 10%). The key secondary cardiovascular composite endpoint of FIDELIO-DKD also showed consistent directional benefit: risks of hospitalization for heart failure and non-fatal myocardial infarction were reduced by 14% and 20%, respectively. In both trials, treatment effects were generally consistent across subgroups (including baseline use of SGLT2i, GLP-1 receptor agonists, and different UACR and eGFR levels).

Renal Protective Effects of Finerenone

The primary renal composite endpoint (kidney failure, sustained eGFR decrease ≥40%, renal death) in FIDELIO-DKD showed that finerenone reduced the absolute risk by 3.4% with a number needed to treat of 29. The treatment effect was mainly reflected in reductions in sustained eGFR decrease ≥40% and progression to kidney failure, with very few renal deaths occurring during the trial. In contrast, the renal composite endpoint (as a key secondary endpoint) in FIGARO-DKD showed a trend favoring finerenone (hazard ratio 0.87) but did not reach statistical significance. In terms of reducing the urine albumin-to-creatinine ratio (UACR), both trials observed an effect of finerenone superior to placebo, achieved across a broad range of chronic kidney disease severity. Real-world studies have further confirmed the UACR-lowering effect, suggesting sustained renal protective effects of the drug.

Adverse Events of Finerenone

Based on pooled data from FIGARO-DKD and FIDELIO-DKD, adverse reactions occurring at an incidence of ≥1% and higher with finerenone versus placebo were again predominantly hyperkalemia (14% vs 6.9%), hypotension (4.6% vs 3%), and hyponatremia (1.3% vs 0.7%). The incidence of reproductive system and breast disorders (e.g., gynecomastia, sexual dysfunction, abnormal bleeding) was similar between the finerenone and placebo groups, consistent with the pharmacological property that finerenone has no relevant affinity for sex hormone receptors. A small increase in serum creatinine and a small decrease in eGFR may also occur after treatment initiation, stabilize within 4 weeks, and are reversible upon discontinuation. Uric acid may also show a transient increase. Dose adjustments or discontinuation due to hyperkalemia should be managed in clinical practice through regular monitoring.