Which blood pressure medication causes angioedema? A look at ACE inhibitors and ARBs

October 10, 2025 •

4 min read

Angiotensin-converting enzyme (ACE) inhibitors are the most common cause of drug-induced angioedema, a rare but potentially life-threatening swelling. This guide explains which blood pressure medication causes angioedema, the underlying mechanism, and safe alternatives for those at risk.

Quick Summary

Angiotensin-converting enzyme (ACE) inhibitors and, less commonly, angiotensin II receptor blockers (ARBs) can cause angioedema due to increased bradykinin levels. This non-itchy swelling primarily affects the face, lips, tongue, and throat, potentially compromising the airway and requiring immediate medical evaluation.

Key Points

ACE Inhibitors are the Primary Cause: Angiotensin-converting enzyme (ACE) inhibitors, including lisinopril, enalapril, and ramipril, are the most common cause of drug-induced angioedema due to their effect on bradykinin.
ARBs Carry a Lower Risk: Angiotensin II receptor blockers (ARBs) like losartan and valsartan also have a rare but documented association with angioedema, and caution is needed when switching from an ACE inhibitor.
Angioedema is Not an Allergy: This medication-induced swelling is not a typical histamine-mediated allergy, meaning standard allergy treatments like antihistamines and steroids are often ineffective.
Symptoms Can Occur at Any Time: The swelling can appear days, months, or even years after starting the medication, and is not necessarily a reaction to the initial dose.
African American Patients Face Higher Risk: Studies consistently show that individuals of African American descent have a higher incidence of ACE inhibitor-induced angioedema.
Alternative Medications are Available: Patients with a history of angioedema can be safely switched to different classes of blood pressure medications, such as calcium channel blockers or diuretics.

Understanding Angioedema and Blood Pressure Medications

Angioedema is a serious adverse effect of certain blood pressure medications, characterized by localized, non-pitting swelling of deep dermal and subcutaneous tissues. The most common areas affected include the face, lips, tongue, and throat. While it may appear similar to an allergic reaction, it is fundamentally different, with a distinct cause and management. In severe cases, the swelling can lead to airway obstruction and be life-threatening. The primary culprits in medication-induced angioedema are angiotensin-converting enzyme (ACE) inhibitors, though angiotensin II receptor blockers (ARBs) also carry a lower risk.

The Link to ACE Inhibitors

ACE inhibitors, a widely prescribed class of drugs for managing hypertension, heart failure, and kidney disease, are the most frequent cause of drug-induced angioedema. This includes common medications such as:

Lisinopril (e.g., Zestril, Prinivil)
Enalapril (e.g., Vasotec)
Ramipril (e.g., Altace)
Captopril (e.g., Capoten)
Perindopril (e.g., Aceon)

The mechanism behind ACE inhibitor-induced angioedema is not a true allergy but is related to the drug's effect on bradykinin. The ACE enzyme (also known as kininase II) typically breaks down bradykinin, a peptide that increases vascular permeability. When ACE is inhibited, bradykinin levels increase, causing fluid to leak from blood vessels into surrounding tissues, resulting in swelling. Angioedema from an ACE inhibitor is not dose-dependent and can occur at any time, from the first dose to years after starting treatment.

The Lower Risk with ARBs

Angiotensin II receptor blockers (ARBs) were developed partly to avoid the bradykinin-related side effects of ACE inhibitors. However, angioedema is still a rare but documented side effect of ARBs, though the risk is significantly lower than with ACE inhibitors. ARBs, such as losartan (Cozaar), valsartan (Diovan), and candesartan (Atacand), do not interfere with the same bradykinin pathway as ACE inhibitors. The mechanism for ARB-induced angioedema is not fully understood but may involve alternative pathways that increase bradykinin levels. Patients with a history of ACE inhibitor-induced angioedema should be extremely cautious, as there is a risk of cross-reactivity.

Comparison of Angioedema Risks


Feature	ACE Inhibitors (e.g., Lisinopril)	Angiotensin II Receptor Blockers (ARBs) (e.g., Losartan)
Incidence of Angioedema	Higher (0.1% to 0.7%)	Lower (much less common, estimated risk 2.5% in patients with previous ACE inhibitor-angioedema)
Mechanism	Inhibits ACE, leading to increased bradykinin levels	May involve alternative mechanisms or pathways, not directly through ACE inhibition
Timing of Onset	Can occur at any time, from weeks to years after starting	Can also occur at any point during therapy
Cross-Reactivity	Contraindicated in those with a history of angioedema from any ACE inhibitor	Caution is advised for switching from an ACE inhibitor to an ARB due to a risk of recurrence
Alternative Therapies	Requires switching to a different class of antihypertensive	Requires switching to a different class of antihypertensive

Key Symptoms and Risk Factors

Angioedema is a clinical diagnosis, and recognizing its symptoms is crucial. The swelling is typically painless and not itchy, distinguishing it from an allergic hive-related reaction. Symptoms can progress quickly and may include:

Swelling of the face, lips, and eyelids
Swelling of the tongue or throat, which can cause difficulty swallowing or breathing
Hoarseness or a "muffled" voice
Abdominal pain, nausea, and vomiting, if the intestinal tract is affected

Certain factors increase an individual's risk of developing angioedema from these medications:

African American descent: Have a significantly higher risk compared to other populations.
Age: Patients over 65 have an increased risk.
Female Sex: Women are more susceptible.
Smoking: A history of smoking increases the risk.
History of angioedema: Prior episodes, even mild ones, increase the risk of a future reaction.
Combination therapy: Taking an ACE inhibitor with a DPP-4 inhibitor (for diabetes) further elevates the risk.

Management and Alternative Therapies

If angioedema is suspected, the offending medication must be discontinued immediately. Prompt medical attention is vital, particularly if the airway is involved. The first priority is to secure the airway, which may require intubation in severe cases. Standard treatments for allergic reactions, such as antihistamines and corticosteroids, are often ineffective because this is not a histamine-mediated response. Newer treatments that target the bradykinin pathway, such as icatibant or fresh frozen plasma, may be used in an emergency setting.

Once an ACE inhibitor is identified as the cause, all drugs within that class must be avoided for life. Alternative blood pressure medications from different classes are available. These include:

Calcium channel blockers: Examples include amlodipine and diltiazem.
Thiazide diuretics: Examples include hydrochlorothiazide.
Beta-blockers: Such as metoprolol or atenolol.

Although ARBs are an alternative, they should be used with caution and careful monitoring in patients with a history of ACE inhibitor-induced angioedema due to the small but present risk of cross-reactivity. Discussion with a healthcare provider is essential to determine the safest alternative.

Conclusion

While angioedema is a rare side effect, its potential severity warrants that patients and healthcare providers understand the link to certain blood pressure medications, especially ACE inhibitors. Awareness of the symptoms, risk factors, and appropriate response is crucial for patient safety. Patients on ACE inhibitors experiencing any signs of unexplained swelling should seek immediate medical help and ensure the medication is promptly stopped. Exploring alternative blood pressure therapies from different drug classes offers a safe path forward for those affected.

For more detailed clinical information on this topic, a helpful resource is the review available on the National Institutes of Health website.

Frequently Asked Questions

The primary blood pressure medication class that causes angioedema is angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril, enalapril, and ramipril.

While the risk is much lower with ARBs, some medical experts advise against it due to a risk of cross-reactivity. Discussing the potential risks versus benefits with a healthcare provider is essential.

ACE inhibitors block an enzyme that normally breaks down bradykinin. This leads to an accumulation of bradykinin, a substance that increases vascular permeability and causes swelling.

Initial signs often include sudden swelling of the lips, tongue, or face. It is typically a non-itchy swelling, which can be distinguished from a typical allergic reaction.

The first step is to immediately stop the medication. Emergency care is needed, especially if the airway is involved. Standard allergy treatments are often ineffective, so specific bradykinin-targeting drugs may be used.

Angioedema can occur at any time while taking the medication, from the first week to several years after starting the treatment.

Safe alternatives often include calcium channel blockers (e.g., amlodipine) and thiazide diuretics (e.g., hydrochlorothiazide). Your doctor can help determine the best option.