Finerenone reduced risk of cardiovascular (CV) death, non-fatal myocardial infarction, non-fatal stroke, and adverse kidney outcomes, according to a pooled analysis of two manufacturer-sponsored randomized trials (RCTs), FIDELIO-DKD and FIGARO-DKD. Both trials randomized patients with chronic kidney disease (CKD) and type 2 diabetes to either the nonsteroidal mineralocorticoid receptor antagonist or placebo.
The analysis was published by the European Heart Journal on Feb. 7. The following commentary by Kaitlin J. Mayne, MBChB, and William G. Herrington, MBBS, MD, was published in the ACP Journal Club section of Annals of Internal Medicine on May 3.
Two large RCTs showed finerenone was effective for CV and kidney outcomes in patients with type 2 diabetes and albuminuric CKD. Prespecified pooling of the RCTs by Agarwal and colleagues allows these effects to be explored with more precision. With finerenone, kidney failure or a doubling of serum creatinine was calculated to be reduced by 22% and hospitalization for heart failure by 22%. These relative risk reductions are similar to observed effects of sodium–glucose cotransporter-2 (SGLT2) inhibitors in placebo-controlled trials. FIDELITY reported that the relative benefits of finerenone on CV outcomes were similar across patient subgroups, but subgroup effects for kidney outcomes were not explored.
Except for hyperkalemia, finerenone appeared to be safe, with no excess risk for serious acute kidney injury. Both RCTs selected participants with serum potassium ≤4.8 mmol/L at screening and implemented careful algorithmic monitoring. Whether based on laboratory data or investigator reports, risk for hyperkalemia with finerenone vs. placebo was approximately doubled. In FIDELIO-DKD, treatment withdrawal or treatment interruption, respectively, were 2.3% and 11.0% in the finerenone group vs. 0.9% and 5.2% for the placebo group. In FIDELITY, permanent treatment withdrawal due to hyperkalemia was 1.7% vs. 0.6%, and serious hyperkalemia was relatively rare with a <1% excess risk for hospitalization for serious hyperkalemia observed over 3 years. In FIDELIO-DKD, other risk factors for hyperkalemia were higher baseline potassium and lower kidney function, whereas concomitant diuretics or an SGLT2 inhibitor—which were prescribed in 57% and 5% of participants, respectively—were both associated with lower risk for hyperkalemia. This is consistent with findings from RCTs in heart failure, which suggest SGLT2 inhibitors vs. placebo reduce risk for severe hyperkalemia and discontinuation of mineralocorticoid receptor antagonists.
Overall, provided that additional blood testing and risk for serious hyperkalemia is acceptable, finerenone offers an important new treatment for patients with type 2 diabetes and albuminuric CKD; combining it with an SGLT2 inhibitor may reduce risk for finerenone-associated hyperkalemia. Whether net benefits extend to patients with nondiabetic forms of CKD and heart failure with preserved ejection fraction are being assessed in ongoing trials.
In other recent diabetes news from Annals of Internal Medicine, Robert M. Centor, MD, MACP, and Fatima Z. Syed, MD, MSc, FACP, discussed the care of adult patients with type 1 diabetes in the May 3 episode of Annals On Call.