Does lisinopril (angiotensin-converting enzyme inhibitor) affect potassium levels?

Lisinopril's Effect on Potassium Levels

Lisinopril increases serum potassium levels and can cause hyperkalemia, particularly in patients with chronic kidney disease or those taking potassium supplements or potassium-sparing medications. 1, 2

Mechanism of Action and Potassium Effects

• Lisinopril inhibits angiotensin-converting enzyme (ACE), which leads to decreased aldosterone secretion, resulting in increased serum potassium levels 2
• In clinical trials, hyperkalemia (serum potassium >5.7 mEq/L) occurred in 2.2% of lisinopril-treated hypertensive patients and 4.8% of heart failure patients 2
• In hypertensive patients with normal renal function treated with lisinopril alone for up to 24 weeks, the mean increase in serum potassium was approximately 0.1 mEq/L; however, about 15% of patients had increases greater than 0.5 mEq/L 2
• This effect contrasts with thiazide diuretics, which typically cause potassium depletion rather than retention 3, 1

Risk Factors for Hyperkalemia with Lisinopril

• Chronic kidney disease significantly increases the risk of hyperkalemia with lisinopril use 4, 5
• Concomitant use of higher doses of ACE inhibitors (including lisinopril ≥10 mg daily) increases the risk of hyperkalemia 3
• Other risk factors include diabetes, heart failure, potassium supplements, and potassium-sparing diuretics 4
• Severe hyperkalemia can develop rapidly even after discontinuation of lisinopril in high-risk patients 5

Clinical Implications and Monitoring

• In the ALLHAT trial, hyperkalemia incidence was greater in patients taking lisinopril (3.6%) compared to chlorthalidone (1.2%) or amlodipine (1.9%) 6
• Hyperkalemia was associated with increased risk of combined cardiovascular disease (hazard ratio, 1.58 [95% CI, 1.15-2.18]) 6
• When lisinopril is administered to patients with severe renal failure, the drug may accumulate, leading to higher serum potassium levels 7
• Potassium levels should be monitored regularly in patients taking lisinopril, particularly those with risk factors for hyperkalemia 3, 1

Management Strategies

• When initiating lisinopril, potassium supplements should be discontinued or reduced and carefully monitored in those with a history of hypokalemia 3
• Patients should be counseled to avoid foods high in potassium and NSAIDs 3
• In patients with hyperkalemia on lisinopril, various strategies can be considered:
  • Adding an SGLT2 inhibitor, which can reduce the risk of serious hyperkalemia (hazard ratio, 0.84; 95% CI, 0.76–0.93) 3
  • Switching to an ARN inhibitor like sacubitril/valsartan, which has lower rates of severe hyperkalemia compared to ACE inhibitors 3
  • Using potassium binders for GDMT maintenance in heart failure patients 3
  • Adjusting the dose or dosing frequency based on the degree of renal function 7

Common Pitfalls and Caveats

• Routine triple combination of an ACE inhibitor, ARB, and aldosterone receptor antagonist should be avoided due to increased hyperkalemia risk 3
• Patients should be instructed to stop aldosterone receptor antagonists (if used with lisinopril) during episodes of diarrhea, dehydration, or when loop diuretic therapy is interrupted 3
• In patients with severe renal failure, adjustment of the lisinopril dose or dosing frequency according to the degree of renal failure is recommended 7
• Hyperkalemia risk increases progressively when serum creatinine is >1.6 mg/dL 3