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

Combining Losartan and Lisinopril Is Not Recommended Due to Increased Risk of Adverse Effects

Taking losartan and lisinopril together is not recommended as this combination causes dual blockade of the renin-angiotensin system (RAS), which increases risks of hypotension, hyperkalemia, and acute kidney injury without providing additional clinical benefits. 1

Why This Combination Should Be Avoided

Mechanism of Concern

• Both medications target the same physiological system:
  • Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor
  • Losartan is an angiotensin II receptor blocker (ARB)
• Using both simultaneously creates excessive blockade of the renin-angiotensin-aldosterone system

Evidence Against Dual RAS Blockade

• The VA NEPHRON-D trial specifically studied the combination of losartan and lisinopril in 1,448 patients with type 2 diabetes and found:
  • No additional benefit compared to monotherapy for renal outcomes or mortality
  • Increased incidence of hyperkalemia and acute kidney injury 1
• Guidelines explicitly state: "Combining two RAS blockers (ACE inhibitor and an ARB) is not recommended" 2
• The 2018 ACC/AHA hypertension guidelines warn that "high-quality RCT data demonstrate that simultaneous administration of RAS blockers increases cardiovascular and renal risk" 2

Alternative Approaches for Hypertension Management

Preferred Combination Strategies

1. RAS blocker (ACE inhibitor OR ARB) + calcium channel blocker
2. RAS blocker (ACE inhibitor OR ARB) + thiazide/thiazide-like diuretic
3. Triple therapy: RAS blocker + calcium channel blocker + diuretic 2

Medication Selection Principles

• First-line treatments should include ACE inhibitors, ARBs, dihydropyridine CCBs, or thiazide diuretics 2
• Fixed-dose single-pill combinations are recommended for improved adherence 2
• When selecting between ACE inhibitors and ARBs, consider:
  • ACE inhibitors commonly cause dry cough (up to 20% of patients)
  • ARBs (like losartan) rarely cause cough, making them suitable alternatives 3

Common Pitfalls to Avoid

Monitoring Requirements

• When using any RAS blocker (ACE inhibitor or ARB):
  • Monitor blood pressure, renal function, and electrolytes 1-2 weeks after starting treatment
  • Recheck after each dose increase
  • Continue monitoring at 3 months and then every 6 months 3

Special Populations at Risk

• Patients with bilateral renal artery stenosis
• Patients with severe congestive heart failure
• Patients with severe sodium and volume depletion
• These patients are particularly sensitive to reduced renal plasma flow and may experience acute renal failure with RAS blockers 4

Dosing Considerations

• Losartan: Initial dose 25-50 mg, maximum dose 50-100 mg once or twice daily 3
• Lisinopril: Initial dose 2.5-5 mg once daily, target dose 20-40 mg once daily 3
• Higher doses of both medications have demonstrated improved clinical outcomes compared to lower doses 3

In conclusion, while both losartan and lisinopril are effective antihypertensive medications individually, their combination should be avoided due to increased risks without additional benefits. If blood pressure control is inadequate with one agent, consider alternative combination strategies as recommended by current guidelines.