Adverse Reactions to ACE Inhibitors and Angiotensin Receptor Blockers

Incidence and Risk Factors

ACE inhibitors can cause adverse reactions in approximately 0.1% to 0.7% of patients, with risk factors for ACE inhibitor-induced angioedema including black race, female sex, history of smoking, increasing age, and history of drug rash 1
Angiotensin-Converting Enzyme (ACE) inhibitors are associated with a higher incidence of cough (up to 20% of patients) and angioedema (less than 1% of patients), more frequently in Black patients 2

Angioedema from ACE inhibitors may occur at any time during treatment and can continue even after discontinuation, and does not reliably respond to treatment with epinephrine, antihistamines, or corticosteroids 1
Discontinuation of the ACE inhibitor (or ARB) is the cornerstone of therapy for drug-associated angioedema 1

For patients with ACE inhibitor-induced angioedema who switch to ARBs, there is a modest risk (2-17%) of recurrent angioedema, but most patients can safely use ARBs without recurrence 1, 2
The American College of Cardiology recommends ARBs as an alternative therapy for patients with a history of ACE inhibitor-induced skin reactions, including cough or angioedema 2
The American College of Cardiology/American Heart Association guidelines recommend ARBs for patients who are ACE inhibitor intolerant due to cough or angioedema 2

Both ACE inhibitors and ARBs require monitoring of blood pressure, renal function, and potassium levels 2, 3
When initiating ARBs, blood pressure, renal function, and potassium should be reassessed within 1-2 weeks 2
When switching from an ACE inhibitor to an ARB due to skin reactions, patients should be monitored closely, especially in the first few weeks, with monitoring of blood pressure, renal function, and potassium levels 1
ARBs are contraindicated in pregnancy (category D) 4
Combination therapy with both an ACE inhibitor and an ARB is generally not recommended due to increased risk of adverse effects without significant additional benefits, according to the American Heart Association 4

Angiotensin Receptor Blockers (ARBs) block angiotensin II receptors directly and do not inhibit kininase, resulting in minimal effect on bradykinin levels, and are associated with a lower incidence of cough and angioedema 5, 3
Despite fewer skin-related adverse effects, ARBs can still cause hypotension, renal dysfunction, hyperkalemia, and rare cases of angioedema 1, 3
The decision to use an ARB instead of an ACE inhibitor should consider the patient's risk factors for skin reactions, previous adverse reactions to ACE inhibitors, and potential benefit vs. harm in the context of the patient's cardiovascular condition 1