Can a patient with an Angiotensin-Converting Enzyme (ACE) inhibitor allergy take an Angiotensin Receptor Blocker (ARB)?

Can a Patient with an ACE Inhibitor Allergy Take an ARB?

Yes, ARBs are recommended as the preferred alternative for patients with ACE inhibitor intolerance, including allergic reactions, though caution is warranted because some patients have also developed angioedema with ARBs. 1

Primary Recommendation

ARBs should be started in patients who cannot tolerate ACE inhibitors due to allergic reactions such as rash or the more serious complication of angioedema. 1 The 2022 AHA/ACC/HFSA guidelines explicitly state that patients who are intolerant to ACE inhibitors because of cough or angioedema should be started on an ARB, as ARBs do not inhibit kininase and are associated with a much lower incidence of these adverse effects. 1

Critical Safety Consideration: Angioedema Risk

While ARBs are the recommended alternative, there is a documented risk of cross-reactivity for angioedema—the most serious concern when switching from an ACE inhibitor after an allergic reaction. 1

• Angioedema occurs in <1% of ACE inhibitor users but is life-threatening when it occurs 1
• Some patients who developed angioedema with ACE inhibitors have also developed angioedema with ARBs 1
• Research indicates a 2-17% risk of cross-reactivity in patients who experienced angioedema with ACE inhibitors 2
• Caution is advised when substituting an ARB in a patient who has had angioedema associated with ACE inhibitor use 1

Clinical Approach for ACE Inhibitor-Allergic Patients

For Non-Angioedema Reactions (e.g., Rash, Cough):

• ARBs are the clear first-line alternative 1, 2
• Cough risk with ARBs is similar to placebo (RR 1.01) and dramatically lower than ACE inhibitors (RR 0.37) 3
• Drug discontinuation rates with ARBs are similar to placebo 3

For Angioedema History:

• ARBs remain an option but require heightened vigilance and informed patient consent 1
• Consider alternative antihypertensive classes if the clinical indication allows (calcium channel blockers, thiazide diuretics, beta-blockers depending on comorbidities) 2
• If ARB is chosen, start with the lowest dose and monitor closely during initiation 1

Initiation and Monitoring Protocol

When starting an ARB in an ACE inhibitor-intolerant patient:

• Start with low doses (e.g., candesartan 4-8 mg daily, losartan 25-50 mg daily, valsartan 20-40 mg twice daily) 4
• Reassess within 1-2 weeks after initiation for blood pressure (including postural changes), renal function, and potassium 1, 2
• Use caution in patients with systolic blood pressure <80 mm Hg, renal insufficiency, or potassium >5.0 mEq/L 1
• Titrate upward toward target doses shown to reduce cardiovascular events in clinical trials 1

Common Pitfalls to Avoid

• Do not rechallenge with ACE inhibitors in patients with previous ACE inhibitor intolerance—the risk of recurrent cough is significantly higher 3
• Do not combine ARBs with ACE inhibitors and aldosterone antagonists—this triple combination is potentially harmful and increases risks of hypotension, renal dysfunction, and hyperkalemia 1
• Do not assume ARBs are completely free of angioedema risk—maintain clinical vigilance, especially in the first weeks of therapy 1

Expected Adverse Effects with ARBs

Compared to placebo, ARBs have higher rates of:

• Hypotension (RR 2.63) 3
• Renal dysfunction (RR 2.07) 3
• Hyperkalemia (RR 3.37) 3

However, overall drug discontinuation rates remain similar to placebo, indicating these effects are generally manageable with appropriate monitoring. 3