Can a patient with hypertension and potential underlying medical conditions such as diabetes or impaired renal function take Losartan (angiotensin II receptor antagonist) with lisinopril (angiotensin-converting enzyme inhibitor)?

No, a patient should not take losartan with lisinopril concurrently

Dual blockade of the renin-angiotensin system (RAS) with both an ARB (losartan) and an ACE inhibitor (lisinopril) is contraindicated and potentially harmful, as it increases risks of hyperkalemia, acute kidney injury, and hypotension without providing additional cardiovascular or renal benefits. 1, 2

Evidence from FDA Drug Labels

Both the FDA-approved drug labels for losartan and lisinopril explicitly warn against dual RAS blockade:

• Losartan label: "Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy." 1

• Lisinopril label: "Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. In most patients no benefit has been associated with using two RAS inhibitors concomitantly. In general, avoid combined use of RAS inhibitors." 2

Clinical Trial Evidence: VA NEPHRON-D Study

The definitive evidence comes from the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, which directly tested this combination:

• Study design: 1,448 patients with type 2 diabetes, elevated urinary albumin-to-creatinine ratio, and decreased eGFR (30-89.9 mL/min) were randomized to receive either losartan plus lisinopril or losartan alone. 1

• Results: Patients receiving the combination of losartan and lisinopril experienced:

  • No additional benefit for the combined endpoint of decline in GFR, end-stage renal disease, or death compared to losartan monotherapy 1
  • Increased incidence of hyperkalemia 1
  • Increased incidence of acute kidney injury 1
  • The trial was terminated early due to adverse events and low conditional power to detect treatment benefit 3

Guideline Recommendations

Multiple authoritative guidelines explicitly recommend against this combination:

• American Heart Association/American College of Cardiology (2013): "Routine combined use of an ACE inhibitor, ARB, and aldosterone antagonist is potentially harmful for patients with HFrEF" (Class III: Harm recommendation). 3

• American Journal of Kidney Diseases (2018): "Two large randomized controlled trials have reported that dual blockade of the renin-angiotensin-aldosterone (RAAS) system is not efficacious for improvement of hard outcomes in NDD-CKD patients and results in adverse events." 3

• ONTARGET trial findings: Secondary analysis showed no improvement in CV events in CKD patients treated with both telmisartan and ramipril compared to either alone, with increased risk of serum creatinine doubling and hyperkalemia. 3

When ARBs Should Be Used Instead of ACE Inhibitors

ARBs like losartan are appropriate alternatives in specific clinical scenarios, but not in combination with ACE inhibitors:

• ACE inhibitor intolerance: ARBs are recommended for patients who cannot tolerate ACE inhibitors (typically due to cough or angioedema). 3

• Similar efficacy: Both drug classes provide comparable cardiovascular and renal protection when used as monotherapy. 4, 5

• Caution with angioedema: Although ARBs may be considered for patients who developed angioedema with ACE inhibitors, some patients have also developed angioedema with ARBs, so caution is advised. 3

Appropriate Combination Strategies

If blood pressure or proteinuria goals are not achieved with monotherapy, the evidence supports these alternatives:

• Add a thiazide diuretic: Combining losartan with hydrochlorothiazide is safe and effective. 6, 7

• Add a calcium channel blocker: Combining an ACE inhibitor or ARB with amlodipine is appropriate. 5

• Add a beta-blocker: This combination is safe when indicated for comorbid conditions. 3

• Titrate to maximum dose: Increasing losartan from 50 mg to 100 mg daily before adding additional agents. 6

Critical Monitoring Parameters

If a patient is inadvertently on both medications, immediate action is required:

• Discontinue one agent (typically continue the one that was initiated first or better tolerated). 1, 2

• Monitor closely for:

  • Serum potassium levels (risk of hyperkalemia) 1, 2
  • Renal function (serum creatinine and eGFR) 1, 2
  • Blood pressure (risk of hypotension) 1, 2

• Reassess within 1-2 weeks after medication adjustment. 3