Angioedema From ACE Inhibitors: What You Need to Know If You Take These Blood Pressure Medications

ACE inhibitors are a category of medications that are a common treatment for high blood pressure. Examples include lisinopril and enalapril. In the U.S., 40 million people take these medications, and they account for ⅓ of all prescribed blood pressure medications. 

These medications play an important role in the health of millions of people. But they have some risks. Less than 1% of people taking ACE inhibitors will have angioedema as a side effect. Given the large number of people who take ACE inhibitors, there’s a good chance ACE inhibitor-induced angioedema will affect you or someone you know. 

When people first experience symptoms, they often don’t recognize the signs or attribute the swelling to other things. But swelling from angioedema can be life-threatening. So we’ll help you recognize the early signs of angioedema that need immediate medical attention. 

What is ACE inhibitor-induced angioedema?

Angioedema refers to swelling of deep tissues — most commonly in the face, mouth, throat, and neck. Many conditions can cause angioedema, from allergic reactions to infections. ACE inhibitors can also cause it. The medical term for this is “ACE inhibitor-induced angioedema.”

Angioedema from ACE inhibitors is not a true allergy. It’s a side effect that can look like one. An effect of these medications is higher levels of the protein bradykinin. 

Bradykinin is a natural part of the body’s inflammatory processes — and it can cause swelling. Most of the time, your body naturally breaks down bradykinin. But some people are less efficient at breaking down bradykinin than others, which puts them at higher risk for angioedema.

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Who is at risk for ACE inhibitor-induced angioedema? 

Anyone who takes ACE inhibitors can develop angioedema. But some people are at increased risk, both from inherited and acquired factors. Risk is particularly high for African Americans, who are 7 times more likely to have angioedema. Other risk factors include:

• Previous episodes of angioedema

• Age older than 65 years

• Female sex

• Smoking

• Treatment with aspirin or NSAIDs (nonsteroidal anti-inflammatory drugs, like ibuprofen)

Symptoms of ACE inhibitor-induced angioedema 

The symptoms of angioedema can vary from person to person. Most often it starts with swelling of the lips, tongue, or face. There are several characteristics of the swelling that are unique to angioedema: 

• Nonsymmetric: Usually the swelling starts on one side of the face or mouth. It’s rarely symmetric. 

• Non-pitting: When you push down on the swollen areas, no finger impressions are left behind. 

• Non-dependent: The swelling is not worse with gravity, like swelling in the lower legs.

• No accompanying itching or hives: This is a helpful way to tell angioedema apart from typical allergic reactions. Other types of angioedema or allergic reactions can be quite itchy and have a pronounced rash. 

Sometimes the swelling can be severe and affect your airway. Life-threatening symptoms include:

• Hoarseness: Swelling deeper down in the throat can affect your voice. Other people may notice this change before you do. 

• Difficulty breathing: You may struggle to get air in or out of your lungs.

• Stridor: This is a noise in your throat that you can hear when breathing in.

• Airway blockage: Sometimes swelling in the throat can close off your airway. This affects about 1 in 10 people who have ACE inhibitor-induced angioedema.

While less common, sometimes ACE inhibitor-induced angioedema can also affect the lining of the gastrointestinal (GI) tract. Instead of swelling to visible areas, like the face, it leads to swelling in the gut. Since it’s less obvious, this can be harder to identify and diagnose. But symptoms of a swollen GI tract include: 

• Abdominal pain

• Vomiting

• Decreased appetite 

• Ascites, or swelling of your abdomen

Timing of symptoms

It’s helpful to know some details about the timing of your symptoms. You can develop angioedema at any time that you’re taking an ACE inhibitor. About half of the people who develop angioedema do so in the first week of starting the ACE inhibitor. But people who have been taking the medication for months or even years can also develop angioedema.

Other important factors about timing include:

• Episodic: This means the swelling comes and goes. You can have periods of swelling that are separated by long periods without symptoms. 

• Onset within minutes to hours: The swelling can start and progress relatively quickly, or the swelling can feel slow and gradual.

• Resolves within 1 to 3 days: For most people, whether they discontinue the medication or not, the swelling is gone within a few days.

• Symptoms that get worse: Angioedema tends to become more frequent and more severe with subsequent episodes.

How do you diagnose ACE inhibitor-induced angioedema?

Your healthcare provider can diagnose ACE inhibitor-induced angioedema based on your symptoms. There’s no specific test to diagnose it. If your provider is concerned that something other than an ACE inhibitor is causing your swelling, they may order labs to help figure it out.

Angioedema that’s in the lining of the GI tract can be trickier to diagnose. If you’re taking an ACE inhibitor and have symptoms, like vomiting and abdominal pain, often imaging can help. In these cases, your healthcare provider may recommend an ultrasound or CT scan of your abdomen. 

How do you treat ACE inhibitor-induced angioedema?

The first step to treating angioedema caused by ACE inhibitors is to stop the medication. If you don’t stop the medication, subsequent episodes of swelling can happen more often. And they can be more severe. Sometimes, despite stopping the ACE inhibitor, episodes of swelling can occur for several months. 

There’s some disagreement among experts whether additional treatments can help decrease the swelling. Researchers are studying a couple of different treatments, but it’s not clear if they’re helpful:

• Bradykinin receptor antagonists: Examples include icatibant and ecallantide. These are expensive medications that need to be given in the hospital. The data is not conclusive on whether or not they are effective. 

• Fresh frozen plasma: This is a blood product that can help break down bradykinin. But this medication is not always used because it can make swelling symptoms worse before they get better.

In some cases it may not be clear that ACE inhibitors are the cause of the angioedema. And the symptoms can also look a lot like an allergic reaction. So sometimes providers will try medications that help other types of angioedema. These include:

• Antihistamines: to treat allergic symptoms

• Steroids: to calm inflammation

• Epinephrine: common in emergency situations when someone’s airway is blocked from swelling 

Since angioedema caused by ACE inhibitors is not an allergic reaction, these therapies are unlikely to help. But they will not harm the condition. 

In severe cases, the treatment priority is to help with breathing. Swelling with angioedema can be so severe that it blocks the airway. In these rare events, medical professionals may need to insert a breathing tube to keep the swelling from blocking off the airway. 

When do you need to seek additional care?

Any degree of swelling in the face, neck, or mouth can be alarming. If your symptoms are mild, you can call your regular provider to figure out the next steps. But more severe cases of angioedema are a medical emergency. 

If you’re having any of the following symptoms, do not wait to speak to your provider. Call 911 and go to the nearest emergency room if you notice:

• Rapid worsening of your swelling

• Swelling of the tongue or throat

• Difficulty breathing or catching your breath

• Noisy breathing, especially if you hear noises when you breathe in (stridor) 

• Change in your voice or hoarseness

Why trust our experts?

Written by:

Jill L. Jaimes, MD

Jill L. Jaimes, MD, is a board-certified pediatric emergency medicine physician with over 20 years of clinical experience. She received her medical degree from Baylor College of Medicine and completed her residency and fellowship training at Texas Children’s Hospital.

Edited by:

Katie E. Golden, MD

Katie E. Golden, MD, is a board-certified emergency medicine physician and a medical editor at GoodRx.

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