Can I prescribe valsartan to a patient with a history of angioedema who is currently taking Entresto (valsartan) for heart failure management?

No, You Cannot Prescribe Valsartan to This Patient

Valsartan is absolutely contraindicated in any patient with a history of angioedema, regardless of whether the angioedema occurred with an ACE inhibitor, ARB, or ARNI like Entresto. 1

Critical Contraindication

The 2022 AHA/ACC/HFSA Heart Failure Guidelines explicitly state that ARNi (which contains valsartan) should not be administered to patients with any history of angioedema (Class 3: Harm recommendation, Level C-LD evidence). 1 This is an absolute contraindication, not a relative one.

Since your patient is currently taking Entresto (sacubitril-valsartan) and has a history of angioedema, they have already demonstrated susceptibility to angioedema while on a valsartan-containing medication. Switching to valsartan alone does not eliminate the risk—it may actually perpetuate or worsen it. 2

Why Valsartan Remains Dangerous

• ARBs including valsartan can cause angioedema independently, even though the mechanism differs from ACE inhibitors. 3, 4
• The FDA drug label for valsartan explicitly warns that angioedema has been reported in postmarketing surveillance, and that "some of these patients previously experienced angioedema with other drugs, including ACE inhibitors." 2
• If angioedema occurred with ANY ARB previously (including the valsartan component of Entresto), that specific ARB and potentially all ARBs are contraindicated. 5, 6
• Cross-reactivity risk exists: patients who develop angioedema with one renin-angiotensin system blocker have a 2-17% risk of recurrence with another agent in the same class. 7

Safer Alternative Medications for Heart Failure

You must discontinue the valsartan-containing medication immediately and choose from these proven alternatives:

First-Line Safe Options (No Cross-Reactivity Risk):

• Beta-blockers (bisoprolol, carvedilol, or metoprolol succinate) remain Class I, Level A recommendations for HFrEF and carry no angioedema risk. 6, 8
• Hydralazine plus isosorbide dinitrate is particularly effective in African American patients and those who cannot tolerate renin-angiotensin system blockade. 8
• Calcium channel blockers (amlodipine only—avoid other calcium antagonists in HFrEF). 8
• Diuretics for volume management. 1
• Spironolactone for NYHA class III-IV symptoms (monitor potassium carefully). 8

Critical Pitfall to Avoid:

Never attempt to "switch" from Entresto to plain valsartan in a patient with angioedema history. The valsartan component is the same drug, and the neprilysin inhibitor (sacubitril) in Entresto actually increases angioedema risk further by impairing bradykinin degradation. 9 Removing sacubitril does not make valsartan safe—the patient has already demonstrated intolerance to the ARB component.

Clinical Action Plan

1. Discontinue Entresto immediately if angioedema occurred while taking it. 1
2. Initiate beta-blocker therapy (if not already on maximum dose) as the cornerstone of HFrEF management. 6, 8
3. Add hydralazine-isosorbide dinitrate combination for additional mortality benefit, especially in African American patients. 8
4. Optimize diuretic therapy for symptom control. 1
5. Document the angioedema history prominently in the medical record as an absolute contraindication to all ARBs and ARNIs. 5

The evidence is unequivocal: a history of angioedema is an absolute contraindication to valsartan in any form. 1, 5 Fortunately, multiple effective alternatives exist that provide mortality benefit without angioedema risk.