Can an Angiotensin-Converting Enzyme (ACE) inhibitor and losartan (Angiotensin II Receptor Blocker (ARB)) be taken together?

ACE Inhibitors and Losartan Should Not Be Taken Together

The combination of an ACE inhibitor and losartan (an ARB) is not recommended due to increased risks of adverse effects without significant clinical benefit.

Rationale Against Dual RAS Blockade

The American College of Cardiology/American Heart Association guidelines clearly state that the routine combined use of ACE inhibitors and ARBs cannot be recommended 1. This recommendation is based on several important findings:

• Dual blockade of the renin-angiotensin system (RAS) increases risks of:
  • Hypotension
  • Worsening renal function
  • Hyperkalemia
  • No additional mortality benefit

The FDA drug label for losartan specifically warns against dual blockade of the RAS, stating that the combination is "associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy" 2.

Evidence Against Combination Therapy

The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial found that patients receiving the combination of losartan and lisinopril:

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

A meta-analysis of randomized controlled trials showed that combination ARB plus ACE inhibitor therapy was associated with:

• 38% increase in medication discontinuations due to adverse effects
• 117% increase in worsening renal function
• 387% increase in hyperkalemia
• 50% increase in symptomatic hypotension 3

Appropriate Use of ACE Inhibitors and ARBs

The guidelines recommend:

1. ACE inhibitors remain first-line therapy for inhibition of the renin-angiotensin system in heart failure 1

2. ARBs should be used as alternatives when patients cannot tolerate ACE inhibitors (typically due to cough or angioedema) 1

3. Monotherapy with either agent is preferred over combination therapy 1

Monitoring Requirements

When using either an ACE inhibitor OR an ARB (not both together):

• Monitor blood pressure (including postural changes)
• Check renal function and potassium within 1-2 weeks of initiation
• Follow closely after dose changes
• Exercise particular caution in patients with:
  • Systolic blood pressure below 80 mmHg
  • Low serum sodium
  • Diabetes mellitus
  • Impaired renal function 1, 4

Special Considerations

The European Society of Cardiology recommends specific target doses for ARBs in heart failure management:

• Candesartan: 32 mg once daily
• Valsartan: 160 mg twice daily
• Losartan: 50-100 mg once daily 4, 1

Conclusion

While both ACE inhibitors and ARBs are effective medications individually, their combination significantly increases the risk of serious adverse effects without providing additional clinical benefit. The evidence strongly supports using either an ACE inhibitor OR an ARB, but not both simultaneously.