Angiotensin II receptor blockers (ARBs) and angioedema

Last updated Dec. 5, 2024, by Lindsey Shapiro, PhD
Fact-checked by Joana Carvalho, PhD

People with angioedema experience swelling attacks in the deep layers of the skin or in the mucus membranes lining internal organs. There are a number of possible underlying causes for these attacks, including adverse reactions to certain medications. This is a type of angioedema known as nonallergic, or drug-induced angioedema.

Angiotensin II receptor blockers (ARBs) are a class of medications used to treat high blood pressure, cardiovascular disease, and kidney disease that can cause nonallergic angioedema. While this is a rare side effect of those medications, patients, especially those with a history of angioedema, should work closely with their doctors to make sure ARBs are safe in their particular case.

Can ARBs cause angioedema?

Drug-induced angioedema is most often associated with a class of medications called angiotensin converting enzyme (ACE) inhibitors. ARBs, which can be prescribed as an alternative to ACE inhibitors, are less likely to trigger angioedema, but have been reported to do so in rare cases. Examples of ARBs linked to angioedema include:

• candesartan (marketed as Atacand and others)
• losartan (marketed as Cozaar and others)
• olmesartan (marketed as Azor and others)
• telmisartan (marketed as Micardis and others)
• valsartan (marketed as Diovan and others).

ARBs help blood vessels relax and improve blood flow by blocking the activation of the renin-angiotensin-aldosterone (RAAS) signaling pathway. They are commonly used to treat conditions such as high blood pressure, heart problems, stroke, and kidney disease.

Used for similar purposes, ACE inhibitors also block the RAAS cascade, but do so differently. One effect of ACE inhibitors is that they directly prevent the degradation of bradykinin, a known driver of angioedema swelling attacks. ARBs, on the other hand, are not known to impact bradykinin levels.

While the relationship between ACE inhibitors and angioedema is well established, much less is known about the link between ARBs and the swelling disorder. Although ARBs have been associated with angioedema attacks in rare instances, the exact mechanisms by which they trigger these episodes remain unclear.

Risk of ARB-induced angioedema

The risk of angioedema attacks triggered by ARBs appears to be generally low. In a large 2012 meta-analysis, such episodes occurred in 0.11% of more than 35,000 people who took ARBs, and the risk of angioedema was more than two times higher with ACE inhibitors than with ARBs. Among those treated in controlled clinical trials, the risk of angioedema attacks was not significantly higher with ARBs than a placebo.

It has also been suggested that angioedema attacks related to ARBs may be less severe than those associated with ACE inhibitors.

While the risk of angioedema is substantially lower with ARBs than with ACE inhibitors, people who have experienced swelling attacks with ACE inhibitors may be at a higher risk of also having them while taking ARBs. Still, there haven’t been any large clinical trials to specifically evaluate this risk and not all studies have observed such an association.

Is it safe to take ARBs if you have angioedema?

Evidence indicates that people who have experienced angioedema while on ACE inhibitors have a 2.5% risk of developing a similar reaction with ARBs. However, this does not mean ARBs must always be avoided by these patients, especially if they are likely to have a large clinical benefit from an ARB.

Patients should always talk about this issue with their healthcare providers, who can help them weigh the potential benefits of ARBs for managing their other health conditions against the possibility of them causing future angioedema attacks.

If a person has a type of angioedema unrelated to medication use, such as hereditary angioedema (HAE), a doctor may determine that ARBs are safe, though this decision will depend on a variety of health factors.

Overall, it’s essential for a person to provide their doctor a thorough medical history, including details of past medications, any previous angioedema attacks, and a family history of angioedema. This information helps doctors make the safest decisions for each particular case. If a doctor recommends taking or avoiding certain medications, it’s also important to follow their guidance and talk with them before making any changes.

When to seek medical attention

Symptoms of an angioedema attack can develop within hours, days, or even months after starting treatment with ARBs. Regardless of when they occur, patients should always seek medical attention, as swelling attacks can affect the airways and become life-threatening.

Signs of a drug-induced angioedema attack may include:

• Swelling, characterized by large smooth welts. Swelling most commonly affects the face, lips, and tongue, but can occur anywhere on the body, including the hands and feet, throat, gut, and genitals. Unlike angioedema caused by an allergic reaction, swelling in nonallergic angioedema is usually not itchy and there are no hives or rash.
• Abdominal pain or other gastrointestinal symptoms caused by swelling in the mucus membranes in and around the intestines.

A doctor can conduct a physical examination and perform other tests to determine if a person is having an angioedema attack and, if so, what interventions are needed.

Treatment for angioedema caused by ARBs is similar to that for other forms of drug-induced angioedema and mainly involves discontinuing the offending medication and finding suitable alternatives. Emergency interventions to open up the airways and secure breathing may also be required in some cases.

Medications commonly used to treat and manage HAE attacks may also be used for drug-induced angioedema. Some reports have indicated that Firazyr (icatibant), an approved on-demand injectable therapy that prevents bradykinin from interacting with its receptor, may be effective for controlling ARB-induced angioedema.

Angioedema News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.