Moderate
Established
Description
Adding spironolactone to an ACE inhibitor substantially increases the risk of hyperkalemia, which can cause life-threatening cardiac arrhythmias.
Mechanism
ACE inhibitors reduce aldosterone secretion (by lowering angiotensin II), decreasing renal potassium excretion; spironolactone antagonizes aldosterone at the tubule, further blocking potassium elimination.
Clinical Significance
Population studies show a 3-fold increase in hyperkalemia hospitalizations with this combination; fatal hyperkalemia-induced arrhythmias have been reported.
Management
Use combination only when evidence-based (heart failure with reduced EF, post-MI); start spironolactone at ≤25 mg/day; monitor potassium and creatinine at 1, 4, and 12 weeks, then every 6 months.