Major
enalapril × spironolactone
Angiotensin-converting enzyme inhibitors (ACEi)×Potassium-sparing diuretics (mineralocorticoid receptor antagonists)
Mechanism
Dual blockade of the renin-angiotensin-aldosterone system. Enalapril reduces aldosterone synthesis while spironolactone blocks the aldosterone receptor – synergistic potassium retention. Risk of severe hyperkalemia (above 6.0 mmol/L) with arrhythmias, particularly in patients over 75, with CKD (eGFR below 45 mL/min), diabetes, or dehydration.
Management
The combination is indicated in HFrEF with LVEF below 35 % (mortality benefit – RALES, EMPHASIS-HF) but requires strict monitoring. Start spironolactone at 12.5–25 mg. Check potassium and creatinine on day 3–5, at 1, 2, 4 weeks, then monthly. If K+ exceeds 5.5 mmol/L, reduce the dose or stop spironolactone. Do not combine with potassium supplements or potassium-containing salt substitutes.
Sources
- RALES Investigators: The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure (1999)— N Engl J Med 1999;341(10):709–717
- EMPHASIS-HF Investigators: Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms (2011)— N Engl J Med 2011;364(1):11–21
- ESC: 2023 Focused Update of the 2021 ESC Guidelines for the treatment of heart failure (2023)— Eur Heart J 2023;44(37):3627–3639
- ESC: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure (2021)— Eur Heart J 2021;42(36):3599–3726