Major
Enalapril × Spironolactone
Angiotensin-converting enzyme inhibitors (ACEi)×Potassium-sparing diuretics (mineralocorticoid receptor antagonists)
Mechanism
Enalapril (an angiotensin-converting enzyme inhibitor, ACE-I) reduces aldosterone synthesis, while spironolactone directly blocks aldosterone receptors. Both retain potassium; hyperkalaemia develops in renal impairment or diabetes.
Symptoms
Muscle weakness, paraesthesia in the limbs, slowed pulse, arrhythmias. ECG shows peaked T waves and widened QRS. Severe cases progress to cardiac arrest. Symptoms typically appear within 1–2 weeks of starting the combination.
Management
The combination is appropriate in heart failure with reduced ejection fraction – a standard regimen. Check potassium and creatinine 1 week after start, then monthly. If potassium exceeds 5.5 mmol/L, stop spironolactone or cut its dose; above 6.0 mmol/L, review both agents.
Sources
- ESC: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure (2021)– Eur Heart J 2021;42(36):3599–3726
- ESC: 2023 Focused Update of the 2021 ESC Guidelines for the treatment of heart failure (2023)– Eur Heart J 2023;44(37):3627–3639
- 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