If you’ve ever had a heart attack or another heart condition, your doctor likely prescribed several medications. Chances are this treatment regimen includes Angiotensin-converting enzyme (ACE) inhibitors. They come in many forms and brand names, but the generic version of the drug usually ends in the suffix “-pril”, like lisinopril or captopril. ACE inhibitors are commonly prescribed for people with high blood pressure, heart failure, diabetes, or chronic kidney disease because these medications are usually safe and effective. Side effects are relatively uncommon but may include dizziness from very low blood pressure, fatigue, headaches, and dry cough. 

An extreme side effect is swelling, which is called angioedema. Such cases are rare and only make up between 0.1% to 0.7% of the many people who take ACE inhibitors. However, ACE inhibitor-induced angioedema is more common in people of African descent and women. Other risk factors include having episodes of angioedema in the past, smoking, being older than 65, and using certain medications. 

Since so many people take ACE inhibitors, even though the risk of angioedema is very low, this medication is responsible for up to 40% of the cases of angioedema in the Emergency Room each year. Physicians will usually first make sure your airway is open if the swelling occurs in your mouth or throat. They will likely replace the ACE inhibitor with another prescription, even if they aren’t sure if the medication caused the angioedema, and caution you to avoid the entire class of medication in the future. 

ACE inhibitor-induced angioedema can develop over the course of a few minutes to over several hours. It usually involves swelling of parts of the face, mouth, and upper airway. In very rare cases, massive tongue or airway swelling can prevent oxygen from entering the lungs leading to suffocation. Sometimes, the intestine can swell which can cause abdominal pain, diarrhea, vomiting, and loss of appetite. Usually, the episode of angioedema resolves on its own over a few days but the swelling can recur. Unlike many allergic reactions to food or drugs, there are no hives or itching associated with the swelling. 

Patients often experience angioedema episodes during the first week of taking an ACE-inhibitor and about two thirds of episodes occur in the first three months of starting the treatment regimen. However, angioedema can occur after years of tolerating the ACE-inhibitor. Some patients experience one or more recurrent angioedema episodes in the months after the causative ACE inhibitor has been discontinued.

There is still much we don’t know about this phenomenon, but a good first step in understanding this side effect is learning about how ACE inhibitors work. Renin, an enzyme in the kidneys, converts Angiotensinogen which is made in the liver to Angiotensin I. The enzyme ACE works in the lungs to convert Angiotensin I to Angiotensin II. Angiotensin-converting enzyme inhibitors stop ACE from making Angiotensin II. Since Angiotensin II constricts your blood vessels and drives up your blood pressure, ACE inhibitors relax these vessels and decrease blood pressure. 

ACE has several jobs in our body’s pathways. Bradykinin is a compound that makes your blood vessels more permeable and opens them up, which can lower your blood pressure. ACE inactivates bradykinin, so inhibiting ACE with medication means increasing the amount of bradykinin in the body. While we aren’t sure about the exact cause of ACE inhibitor-induced angioedema, it may be due to having too much bradykinin or similar compounds in the body. This can cause fluid build-up in the blood vessels and surrounding tissues, which leads to swelling in the area. 

ACE inhibitors are often the first line of treatment for high blood pressure and other conditions, and most people who take them experience few to no side effects. ACE inhibitor-induced angioedema is rare and please consult with your physician if you have any questions or concerns.