Can losartan (angiotensin II receptor antagonist) cause hypokalemia (low potassium levels)?

Losartan Does Not Cause Hypokalemia but Rather Increases Risk of Hyperkalemia

Losartan (an angiotensin II receptor blocker) does not cause hypokalemia but instead increases the risk of hyperkalemia, particularly when combined with other medications that affect potassium levels. 1

Mechanism of Action and Potassium Effects

Losartan, as an angiotensin II receptor blocker (ARB), works by blocking the renin-angiotensin-aldosterone system (RAAS), which leads to decreased aldosterone production. This mechanism:

• Reduces potassium excretion in the kidneys
• Can lead to potassium retention rather than depletion
• Is specifically listed among medications that can cause hyperkalemia (elevated potassium) 1

The European Society of Cardiology's expert consensus document clearly identifies ARBs like losartan as medications that decrease potassium excretion, potentially causing hyperkalemia 1.

Clinical Evidence

Recent research from the HEAAL trial (2023) demonstrated that:

• High-dose losartan (150 mg/day) actually decreased the risk of hypokalemia compared to low-dose (50 mg/day) with HR 0.77 (95% CI 0.63-0.92)
• High-dose losartan increased the risk of hyperkalemia with HR 1.21 (95% CI 1.05-1.39)
• Hypokalemia was associated with worse outcomes than hyperkalemia in heart failure patients 2

Risk Factors for Hyperkalemia with Losartan

The risk of hyperkalemia with losartan increases when:

• Combined with other potassium-sparing medications (spironolactone, eplerenone, triamterene)
• Used in patients with impaired renal function
• Used in patients with diabetes
• Combined with potassium supplements 1, 3

Monitoring Recommendations

When starting losartan:

• Monitor serum potassium within 1-2 weeks after initiation
• Continue monitoring every 3-6 months once stable
• Be particularly vigilant in patients with risk factors for hyperkalemia 3

Clinical Implications

• When managing hypertension, if potassium depletion is a concern, losartan would actually be beneficial as it tends to raise potassium levels
• For patients already experiencing hyperkalemia, losartan may need to be used cautiously or avoided 3
• In heart failure patients, the benefits of losartan on cardiovascular outcomes persist across the spectrum of serum potassium levels 2

Common Pitfalls

1. Confusing ARBs like losartan with thiazide diuretics, which do cause hypokalemia
2. Failing to monitor potassium levels when starting losartan, especially in high-risk patients
3. Not recognizing potential drug interactions that could compound hyperkalemia risk (e.g., combining losartan with spironolactone) 4, 5
4. Overlooking that losartan can actually protect against hypokalemia when used with medications that lower potassium 2

In conclusion, when considering medications that affect potassium balance, losartan should be recognized as a medication that increases potassium levels rather than depletes them, making it useful in situations where potassium preservation is desired but requiring careful monitoring to prevent hyperkalemia.