FINERENONE (KERENDIA®)



















FIDELIO-DKD study - Finerenone vs Placebo for CKD Outcomes in Patients with Type 2 DM and Kidney Disease, NEJM (2020) [PubMed abstract]
  • The FIDELIO-DKD trial enrolled 5734 patients with type 2 diabetes and CKD
Main inclusion criteria
  • Type 2 diabetes
  • Treated with maximally-tolerated ACE/ARB
  • CKD defined as one of the following:
    • Urine ACR 30 to <300 + GFR 25 - 59 ml/min + diabetic retinopathy
    • Urine ACR 300 - 5000 + GFR 25 - 74 ml/min
Main exclusion criteria
  • Serum potassium > 4.8 mEq/L
  • Non-diabetic kidney disease
  • HgA1C > 12%
  • SBP ≥ 170, DBP ≥ 110
  • NYHA class II - IV HFrEF
Baseline characteristics
  • Average age 66 years
  • Average A1C - 7.7%
  • Average GFR - 44.3 ml/min
  • Median ACR - 852
  • Average SBP - 138 mmHg
Randomized treatment groups
  • Group 1 (2833 patients): Finerenone group: GFR 25 - 59 ml/min: 10 mg once daily | GFR ≥ 60 ml/min: 20 mg once daily
  • Group 2 (2841 patients): Placebo
  • For those starting at 10 mg, an increase in the dose from 10 to 20 mg once daily was encouraged after 1 month, provided the serum potassium level was ≤ 4.8 mEq/L and the GFR was stable
  • Study drug was held if potassium exceeded 5.5 mEq/L and restarted when potassium fell to ≤ 5 mEq/L
  • A decrease in the dose from 20 to 10 mg once daily was allowed any time after the initiation of finerenone or placebo
  • Concomitant eplerenone, spironolactone, any renin inhibitor, or potassium-sparing diuretic was not allowed
  • Average finerenone dose during the study was 15.1 mg
Primary outcome: Composite of kidney failure, a sustained decrease of at least 40% in the eGFR from baseline over a period of at least 4 weeks, or death from renal causes
Results

Duration: Median of 2.6 years
Outcome Finerenone Placebo Comparisons
Primary outcome 17.8% 21.1% HR 0.82, 95%CI [0.73 - 0.93], p=0.001
Kidney failure 7.3% 8.3% HR 0.87, 95%CI [0.72 - 1.05]
GFR decrease ≥ 40% 16.9% 20.3% HR 0.81, 95%CI [0.72 - 0.92]
Death from renal causes <0.1% <0.1% N/A
Overall mortality 7.7% 8.6% HR 0.90, 95%CI [0.75 - 1.07]
Hyperkalemia 18.3% 9% N/A
Serious hyperkalemia 1.6% 0.4% N/A
  • The finerenone group achieved an average SBP that was about 3 mmHg lower than the placebo group
  • The finerenone group had an average reduction in the urinary ACR of about 30% over the course of the trial compared to no change in the placebo group
  • The estimated decrease in eGFR over the course of 44 months was 12 ml/min in the finerenone group and 14 ml/min in the placebo group

Findings: In patients with CKD and type 2 diabetes, treatment with finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo.
FIGARO-DKD study - Finerenone vs Placebo for CVD Outcomes in Patients with Type 2 DM and Kidney Disease, NEJM (2021) [PubMed abstract]
  • The FIGARO-DKD study enrolled 7437 patients with type 2 diabetes and CKD
Main inclusion criteria
  • Type 2 diabetes
  • Treated with maximally-tolerated ACE/ARB
  • CKD defined as one of the following:
    • Urine ACR 30 to <300 + GFR 25 - 90 ml/min
    • Urine ACR 300 - 5000 + GFR ≥ 60 ml/min
Main exclusion criteria
  • Serum potassium > 4.8 mEq/L
  • Non-diabetic kidney disease
  • HgA1C > 12%
  • SBP ≥ 170, DBP ≥ 110
  • NYHA class II - IV HFrEF
Baseline characteristics
  • Average age 64 years
  • Average A1C - 7.7%
  • Average GFR - 68 ml/min
  • Median ACR - 308
  • Average SBP - 136 mmHg
  • History of CVD - 45%
Randomized treatment groups
  • Group 1 (3686 patients): Finerenone group: GFR 25 - 59 ml/min: 10 mg once daily | GFR ≥ 60 ml/min: 20 mg once daily
  • Group 2 (3666 patients): Placebo
  • For those starting at 10 mg, an increase in the dose from 10 to 20 mg once daily was encouraged after 1 month, provided the serum potassium level was ≤ 4.8 mEq/L and the GFR was stable
  • Study drug was held if potassium exceeded 5.5 mEq/L and restarted when potassium fell to ≤ 5 mEq/L
  • A decrease in the dose from 20 to 10 mg once daily was allowed any time after the initiation of finerenone or placebo
  • Concomitant eplerenone, spironolactone, any renin inhibitor, or potassium-sparing diuretic was not allowed
  • Average finerenone dose during the study was 17.5 mg
Primary outcome: Composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure
Results

Duration: Median of 3.4 years
Outcome Finerenone Placebo Comparisons
Primary outcome 12.4% 14.2% HR 0.87, 95%CI [0.76 - 0.98], p=0.03
Death from CV causes 5.3% 5.8% HR 0.90, 95%CI [0.74 - 1.09]
Nonfatal MI 2.8% 2.8% HR 0.99, 95%CI [0.76 - 1.31]
Nonfatal stroke 2.9% 3.0% HR 0.97, 95%CI [0.74 - 1.26]
Hospitalization for heart failure 3.2% 4.4% HR 0.71, 95%CI [0.56 - 0.90]
Overall mortality 9.0% 10.1% HR 0.89, 95%CI [0.77 - 1.04]
Hyperkalemia 10.8% 5.3% N/A
Serious hyperkalemia 0.7% 0.1% N/A
  • The finerenone group achieved an average SBP that was about 3 mmHg lower than the placebo group

Findings: Among patients with type 2 diabetes and stage 2 to 4 CKD with moderately elevated albuminuria or stage 1 or 2 CKD with severely elevated albuminuria, finerenone therapy improved cardiovascular outcomes as compared with placebo.
























  • If eGFR has decreased by more than 30% compared to previous measurement, maintain 10 mg dose
Dose Adjustment Based on Serum Potassium
Current finerenone dose
Potassium level (mEq/L) 10 mg 20 mg
≤ 4.8 Increase the dose to 20 mg once daily Maintain 20 mg once daily
>4.8 - 5.5 Maintain 10 mg once daily Maintain 20 mg once daily
> 5.5
  • Withhold finerenone
  • Consider restarting at 10 mg once daily when serum potassium ≤ 5.0 mEq/L
  • Withhold finerenone
  • Restart at 10 mg once daily when serum potassium ≤ 5.0 mEq/L