Is it safe to use finerenone and Angiotensin-Converting Enzyme (ACE) inhibitors together?

Finerenone and ACE Inhibitor Combination Therapy in Chronic Kidney Disease

The combination of finerenone and ACE inhibitors should be used with caution due to increased risk of hyperkalemia, but can be safely administered with appropriate monitoring in patients with chronic kidney disease and type 2 diabetes. 1

Safety and Efficacy of the Combination

• Mineralocorticoid receptor antagonists (MRAs) like finerenone in combination with ACE inhibitors remain an area of clinical interest due to their complementary mechanisms in reducing albuminuria and providing cardiovascular benefits 1
• Finerenone is a non-steroidal MRA that has shown significant benefits in reducing composite endpoints related to progression of renal disease and cardiovascular disease in patients with chronic kidney disease and type 2 diabetes 1, 2
• The combination has been studied in clinical trials where patients were already taking renin-angiotensin system inhibitors (including ACE inhibitors) and then had finerenone added to their regimen 1, 3

Hyperkalemia Risk and Management

• The primary concern with combining finerenone and ACE inhibitors is the increased risk of hyperkalemic episodes, which has been observed in clinical studies 1
• In the FIDELIO-DKD trial, hyperkalemia occurred in 10.8% of patients on finerenone (who were also on ACE inhibitors or ARBs) compared to 5.3% in the placebo group, though only 1.2% discontinued treatment due to hyperkalemia 1
• Risk factors for hyperkalemia include:
  • Declining renal function (lower eGFR) 2
  • Concomitant use of other potassium-sparing medications 1
  • Higher baseline serum potassium levels 1

Monitoring Recommendations

• Regular monitoring of serum potassium levels is essential when using this combination, particularly:
  • At baseline before initiating therapy
  • Within the first month after starting treatment
  • After any dose adjustments
  • Periodically during continued therapy 1
• Renal function should also be monitored regularly, as declining eGFR increases hyperkalemia risk 2

Dosing Considerations

• Starting with lower doses of finerenone (10 mg daily) is recommended for patients with eGFR 25-60 mL/min/1.73 m² 1
• Dose can be increased to 20 mg daily after one month if serum potassium is ≤4.8 mmol/L and eGFR remains stable 1
• Consider early initiation of this combination when renal function is still relatively preserved to minimize side effects 2

Contraindications and Precautions

• The combination of ACE inhibitors with ARBs should be avoided due to increased risk of adverse events (hyperkalemia and/or acute kidney injury) without additional benefits 1
• Use with caution in patients with:
  • Advanced kidney disease (eGFR <30 mL/min/1.73 m²)
  • History of hyperkalemia
  • Concomitant use of other potassium-sparing medications 1

Clinical Benefits of the Combination

• The combination targets different pathways in the renin-angiotensin-aldosterone system, potentially providing complementary cardiorenal protection 4, 5
• Preclinical studies have shown that combining MRAs with RAAS inhibitors can provide additive benefits in reducing proteinuria and blood pressure 5
• Recent evidence suggests that triple therapy with ACE inhibitors/ARBs, finerenone, and SGLT2 inhibitors may be a promising approach for comprehensive cardiorenal protection 2, 3

Alternative Approaches

• If hyperkalemia becomes a persistent issue, consider:
  • Using potassium binders to allow continued use of both medications 2
  • Adjusting doses of either medication rather than discontinuing completely 2
  • Switching from ACE inhibitor to calcium channel blocker if appropriate for the patient's condition 6

By carefully monitoring serum potassium and renal function, the combination of finerenone and ACE inhibitors can be safely used to provide cardiorenal protection in appropriate patients with chronic kidney disease and type 2 diabetes.