Is losartan (angiotensin II receptor antagonist) compatible with lisinopril (angiotensin-converting enzyme inhibitor) for hypertensive control?

Losartan and Lisinopril Should Not Be Used Together for Hypertension Control

Losartan and lisinopril should not be used in combination for hypertension control as this dual RAAS blockade increases adverse effects without providing significant additional benefit in blood pressure reduction or cardiovascular outcomes. 1

Mechanism of Action and Overlap

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 prevents angiotensin II from binding to its receptors

Evidence Against Combination Therapy

The ONTARGET trial and other studies have demonstrated that combining ACE inhibitors and ARBs:

• Does not provide superior blood pressure control compared to monotherapy with either agent 1
• Increases the risk of adverse effects, particularly:
  • Hypotension
  • Hyperkalemia
  • Worsening renal function 1

In the VALIANT trial, the combination of valsartan (an ARB) and captopril (an ACE inhibitor) showed no increased effect over captopril alone but had a higher incidence of discontinuation due to adverse effects 1.

Appropriate Use of These Medications

Monotherapy Options

Both medications are effective as monotherapy for hypertension:

• Losartan: Effective once-daily antihypertensive agent with efficacy similar to enalapril, atenolol, and felodipine 2
• Lisinopril: Effective ACE inhibitor with proven benefits in hypertension control 1

Sequential Use (Not Combination)

ARBs like losartan are appropriate alternatives when ACE inhibitors like lisinopril cause intolerable side effects:

• For ACE inhibitor-induced cough: Losartan is a suitable alternative, as ACE inhibitor-related cough occurs in up to 20% of patients but is rare with ARBs 1, 3
• For angioedema: ARBs may be considered as alternative therapy, though with extreme caution as some patients have developed angioedema with both classes 1

Clinical Decision Algorithm

1. Start with either lisinopril or losartan as monotherapy (not both)

   • Consider patient characteristics (diabetes, CKD, heart failure)
   • Initial dosing: Lisinopril 2.5-5 mg once daily or Losartan 25-50 mg once daily 1

2. If blood pressure goal not achieved:

   • Optimize the dose of the chosen medication
   • Lisinopril can be titrated up to 20-40 mg daily
   • Losartan can be titrated up to 50-100 mg daily 1

3. If still not at goal or side effects occur:

   • Add a thiazide diuretic or calcium channel blocker (not the other RAAS inhibitor) 4
   • If ACE inhibitor causes cough, switch to ARB 1, 3

4. For resistant hypertension:

   • Consider adding a calcium channel blocker and/or mineralocorticoid receptor antagonist 4
   • Do not combine ACE inhibitor and ARB

Monitoring Recommendations

When using either medication:

• Check serum potassium and renal function within 3 months of starting therapy 4
• Monitor for metabolic effects: glucose, uric acid, and lipid levels 4
• Follow up 4-12 weeks after initiation to assess blood pressure control and adverse effects 4

Special Considerations

• Diabetes or CKD: Both ACE inhibitors and ARBs are preferred first-line agents, but should not be used together 4
• Heart failure: ACE inhibitors have strong evidence for reducing mortality; ARBs are alternatives for those intolerant to ACE inhibitors 1
• African American patients: May have less robust response to ACE inhibitors or ARBs; consider starting with thiazide diuretic or calcium channel blocker 4

Remember that the goal of antihypertensive therapy is to achieve blood pressure control while minimizing adverse effects. Using two RAAS blockers simultaneously increases risks without providing additional benefits.