Can you take losartan (angiotensin II receptor antagonist) and lisinopril (angiotensin-converting enzyme inhibitor) together?

Losartan and Lisinopril Should Not Be Used Together Due to Increased Risk of Adverse Effects

Taking losartan and lisinopril together is not recommended due to increased risks of hypotension, hyperkalemia, and acute kidney injury without additional therapeutic benefit. 1, 2

Mechanism and Rationale

Both medications target the renin-angiotensin-aldosterone system (RAAS) but through different mechanisms:

• Lisinopril: An angiotensin-converting enzyme (ACE) inhibitor that prevents the conversion of angiotensin I to angiotensin II
• Losartan: An angiotensin II receptor blocker (ARB) that blocks the binding of angiotensin II to its receptor

Evidence Against Dual RAAS Blockade

The evidence strongly discourages combining these medications:

• The VA NEPHRON-D trial specifically studied the combination of losartan and lisinopril in patients with type 2 diabetes and found that patients receiving both medications:

  • Did not obtain additional benefit compared to monotherapy
  • Experienced increased incidence of hyperkalemia and acute kidney injury 2

• The 2017 ACC/AHA hypertension guidelines explicitly state: "High-quality RCT data demonstrate that simultaneous administration of RAS blockers (i.e., ACE inhibitor with ARB; ACE inhibitor or ARB with renin inhibitor aliskiren) increases cardiovascular and renal risk" 1

• The guidelines further recommend: "Drug combinations that have similar mechanisms of action or clinical effects should be avoided" 1

Potential Adverse Effects of Combination Therapy

Combining losartan and lisinopril can lead to:

1. Hyperkalemia: Both medications can increase serum potassium levels 2
2. Acute kidney injury: Dual RAAS blockade increases risk of renal dysfunction 2
3. Hypotension: Excessive blood pressure lowering may occur 1
4. Syncope: Due to severe hypotension 2

Appropriate Alternative Approaches

For patients requiring multiple antihypertensive medications:

• Complementary mechanisms: Choose medications from different classes with complementary mechanisms of action 1

  • Example: Thiazide diuretic + ACE inhibitor OR ARB (not both)
  • Example: Calcium channel blocker + ACE inhibitor OR ARB (not both)

• Fixed-dose combinations: Several two-drug combinations are available with complementary mechanisms 1

Special Considerations

• Switching between medications: When switching from lisinopril to losartan, the equivalent dose is 50 mg once daily, with potential titration to 100-150 mg daily as needed 3

• Monitoring: When using either medication alone, monitor:

  • Blood pressure
  • Renal function
  • Potassium levels
  • Follow-up within 1-2 weeks after starting treatment or dose changes 3

Conclusion

The evidence clearly demonstrates that combining losartan and lisinopril provides no additional benefit while significantly increasing risks of adverse effects. Patients should be treated with either an ACE inhibitor OR an ARB, but not both simultaneously.