What is the risk of hyperkalemia with lisinopril (Angiotensin-Converting Enzyme Inhibitor) compared to losartan (Angiotensin II Receptor Blocker)?

Hyperkalemia Risk: Lisinopril vs Losartan

Both lisinopril (ACE inhibitor) and losartan (ARB) can cause hyperkalemia, but lisinopril poses a higher risk of hyperkalemia compared to losartan due to its more potent effects on the renin-angiotensin-aldosterone system.

Mechanism of Hyperkalemia with RAAS Inhibitors

• Both ACE inhibitors (like lisinopril) and ARBs (like losartan) can cause hyperkalemia by decreasing aldosterone production, which reduces potassium excretion in the distal tubule of the kidney 1
• These medications are listed as primary agents that can cause hyperkalemia in cardiovascular disease management guidelines 1
• The risk of hyperkalemia is particularly increased in patients with chronic kidney disease (CKD) or in those taking potassium supplements or potassium-sparing drugs 1

Comparative Risk: Lisinopril vs Losartan

• ACE inhibitors like lisinopril are associated with a higher incidence of hyperkalemia compared to ARBs like losartan 1
• The FDA drug label for lisinopril specifically mentions that hyperkalemia (serum potassium greater than 5.7 mEq/L) occurred in 2.2% of hypertensive patients and 4.8% of heart failure patients treated with lisinopril 2
• ARBs like losartan have a more selective mechanism of action on the renin-angiotensin system, which may contribute to their lower risk of hyperkalemia compared to ACE inhibitors 1

Risk Factors for Hyperkalemia with RAAS Inhibitors

• Renal impairment (eGFR <60 mL/min/1.73m²) significantly increases the risk of hyperkalemia with both medications 3
• Diabetes mellitus increases the risk of hyperkalemia with both medications 3, 4
• Heart failure is an independent risk factor for developing hyperkalemia with RAAS inhibitors 3, 5
• Advanced age (>70 years) increases the risk of severe hyperkalemia 5
• Concomitant use of other medications that can increase potassium levels:
  • Potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride) 1
  • Potassium supplements 1
  • NSAIDs 6
  • Beta-blockers 1

Incidence of Hyperkalemia

• Approximately 11% of outpatients using ACE inhibitors develop hyperkalemia (potassium >5.1 mmol/L) 5
• In a large health system study, potassium levels >5 mEq/L occurred in 10.8% of patients on antihypertensive medications over a 3-year period 4
• The antihypertensive medication class most strongly associated with hyperkalemia was ACE inhibitors 4
• Severe hyperkalemia (potassium >6.0 mmol/L) developed in 10% of patients who continued ACE inhibitor therapy after an initial episode of hyperkalemia 5

Clinical Implications and Management

• Regular monitoring of serum potassium is essential when initiating or adjusting doses of either medication 7
• Baseline assessment of renal function and serum potassium should be performed before starting either medication 7
• More frequent monitoring is recommended for high-risk patients (CKD, diabetes, heart failure, elderly) 3, 5
• Loop or thiazide diuretics can reduce the risk of hyperkalemia when used concurrently with ACE inhibitors or ARBs 5
• In patients with a history of hyperkalemia, switching from an ACE inhibitor (lisinopril) to an ARB (losartan) may be beneficial 4, 7
• Avoid dual RAAS blockade (combining ACE inhibitors and ARBs) as this significantly increases the risk of hyperkalemia without additional clinical benefit 1, 6

Special Considerations

• In patients with heart failure, the benefits of RAAS inhibition often outweigh the risks of hyperkalemia, but careful monitoring is essential 1
• For patients with CKD, the risk of hyperkalemia increases gradually with declining eGFR, with no clear threshold for contraindicating these medications 3
• Patients with a previous episode of hyperkalemia on an ACE inhibitor may tolerate an ARB with appropriate monitoring 1