Should perindopril (Angiotensin-Converting Enzyme Inhibitor) be withheld in a patient with Heart Failure with Reduced Ejection Fraction (HFrEF) and Impaired Renal Function, specifically with an estimated Glomerular Filtration Rate (eGFR) of 21?

From the Guidelines

I strongly recommend continuing perindopril in this patient with heart failure with reduced ejection fraction (HFrEF) and an eGFR of 21 mL/min/1.73m², as the benefits of ACE inhibitors in reducing morbidity and mortality outweigh the risks, as supported by the 2017 ACC/AHA/HFSA guideline update 1. The use of ACE inhibitors like perindopril is beneficial for patients with prior or current symptoms of chronic HFrEF to reduce morbidity and mortality, as established by large randomized controlled trials 1.

• Key considerations for ACE inhibitor use in patients with low eGFR include:
  • Starting at low doses and titrating upward to minimize risks of worsening renal function and hyperkalemia
  • Monitoring renal function and potassium levels closely, initially after 1 week of treatment and then every 2-4 weeks until stable
  • Being vigilant for potential adverse effects including worsening renal function, hyperkalemia, and hypotension
  • Ensuring the patient stays well-hydrated but avoids excessive fluid intake given their heart failure
  • Considering a gradual increase in dose if the patient tolerates the initial dose well and if needed for optimal heart failure management
• The 2017 ACC/AHA/HFSA guideline update 1 and the 2015 American Heart Association and Heart Failure Society of America scientific statement 1 support the use of ACE inhibitors in patients with HFrEF, including those with reduced renal function, as long as they are used with caution and careful monitoring.
• It is crucial to weigh the potential benefits of ACE inhibitors against the risks in patients with low eGFR, and to individualize treatment decisions based on the patient's specific clinical circumstances and preferences, as recommended by the guidelines 1.

From the FDA Drug Label

Dose Adjustment in Renal Impairment Kinetic data indicate that perindoprilat elimination is decreased in renally impaired patients, with a marked increase in accumulation when creatinine clearance drops below 30 mL/min. In such patients (creatinine clearance <30 mL/min), safety and efficacy of perindopril erbumine tablets have not been established For patients with lesser degrees of impairment (creatinine clearance above 30 mL/min), the initial dosage should be 2 mg/day and dosage should not exceed 8 mg/day due to limited clinical experience.

Unholding perindopril is not recommended for a patient with HFrEF and eGFR 21, as the safety and efficacy of perindopril erbumine tablets have not been established in patients with creatinine clearance <30 mL/min 2.

From the Research

Unholding Perindopril in Patients with HFrEF and eGFR 21

• The decision to unhold perindopril in a patient with heart failure with reduced ejection fraction (HFrEF) and an estimated glomerular filtration rate (eGFR) of 21 mL/min/1.73 m2 should be based on careful consideration of the patient's overall clinical condition and the potential benefits and risks of continuing renin-angiotensin-aldosterone system (RAAS) blockade 3, 4.
• RAAS blockers, such as perindopril, are a life-saving treatment for patients with HFrEF, regardless of worsening renal function, and should be continued unless there are compelling reasons to stop them 3.
• The presence of chronic kidney disease (CKD) in a patient with HFrEF should not preclude the use of a RAAS inhibitor, although patients should be monitored frequently for worsening renal function and hyperkalemia 5.
• In patients with HFrEF and advanced CKD (eGFR ≤ 30 mL/min/1.73 m2), angiotensin receptor-neprilysin inhibitors (ARNIs) have been shown to be safe and effective, with comparable clinical and renal outcomes to angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) 6.
• However, the use of ARNIs in patients with HFrEF and advanced CKD should be approached with caution, as they may be associated with a higher incidence of heart failure hospitalization, especially in patients on dialysis 6.

Key Considerations

• Before changing treatment, consider the presence of concomitant disorders that could alter renal function status, congestion/dehydration status, blood pressure, and intake of nephrotoxic drugs 3.
• Close biological monitoring after treatment modification is mandatory to ensure that the patient's renal function and potassium levels are stable 3, 4.
• The decision to unhold perindopril should be based on a comprehensive assessment of the patient's clinical condition, including their renal function, blood pressure, and overall cardiovascular risk 4, 5.