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Bowel-ed over by ACE inhibitors and angiotensin II receptor blockers: When angioedema hits the intestines

Published: 4 December 2025
Prescriber Update 46(4): 57–59
December 2025

Key messages

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) can cause angioedema in any mucosal surface, and typically affects the tongue, face and upper airway.
Angioedema can also occur in the intestines. It is likely to be under-recognised and underreported as it is less obvious than when it occurs in other locations.
Consider intestinal angioedema in patients taking an ACE inhibitor or ARB who present with non-specific symptoms such as abdominal pain, diarrhoea, nausea or vomiting.

At their September 2025 meeting, the Medicines Adverse Reactions Committee reviewed the risk of intestinal angioedema with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs).

This article highlights the risk of angioedema with these medicines, with a focus on intestinal angioedema.

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers

ACE inhibitors and ARBs (Table 1) act on the renin-angiotensin-aldosterone system. This system regulates blood volume, electrolyte balance and systemic vascular resistance.¹

Table 1: Approved angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) in New Zealand, 1 October 2025

ACE inhibitors	ARBs
Captopril Enalapril Lisinopril Perindopril Quinapril Ramipril	Candesartan Irbesartan Losartan Valsartan*

* Valsartan is only available as part of the combination product Entresto, which also contains the neprilysin inhibitor sacubitril. Neprilysin inhibitors prevent the degradation of vasoactive substances, including natriuretic peptides, bradykinin and angiotensin II.

Source: Medsafe Product/Application search, accessed 1 October 2025.

Angioedema with ACE inhibitors and ARBs

Angioedema is a localised subcutaneous or submucosal swelling caused by extravasation (leakage) of fluid into interstitial tissues.² Any mucosal tissue can be involved, although angioedema typically affects the tongue, face and upper airway.³

ACE inhibitors are thought to cause angioedema due to a build-up of bradykinin.³ ACE inhibitor-induced angioedema is rare, occurring in around 0.1% to 0.7% of patients treated with this class of medicines.³ ACE inhibitors are contraindicated in patients with a previous episode of angioedema from an ACE inhibitor.⁴

The risk of developing angioedema is lower with ARBs compared with ACE inhibitors.⁵ Some studies suggest that the risk of angioedema with ARBs is similar to other antihypertensives (eg, beta-blockers) and placebo.⁵The mechanism of ARB-induced angioedema is unknown.⁶

Use of ARBs is not contraindicated in people who have experienced angioedema with an ACE inhibitor.⁴ The reoccurrence of angioedema after switching to an ARB has been reported to occur in 1.5% of patients.⁷

Sacubitril + valsartan is contraindicated in patients with a known history of ACE inhibitor or ARB-induced angioedema.⁸

Intestinal angioedema – a presentation to keep in mind

Angioedema can also occur in the mucosal tissue of the intestines, with or without other sites being affected.⁵ Intestinal angioedema is likely to be under-recognised and underreported as it is less obvious than when it occurs in the tongue, face and upper airway.⁵

Patients can also present with non-specific gastrointestinal symptoms, such as abdominal pain, diarrhoea, nausea or vomiting.³ As many other conditions and diseases have these same symptoms, diagnosing intestinal angioedema can be challenging.³

There are reports of patients undergoing unnecessary procedures in attempts to exclude other possible causes.⁹ Some patients also report their symptoms as self-limiting, resolving within 2 to 3 days even without discontinuing the suspected medicine.¹⁰ Patients may have bouts of intestinal angioedema for many years before being diagnosed.¹⁰

Consider intestinal angioedema in patients who are using an ACE inhibitor or ARB, and:⁹

have abdominal pain with or without other gastrointestinal symptoms
computerised tomography or ultrasound of abdomen or pelvis showing bowel wall thickening with or without ascites
have normal C1-esterase inhibitor levels
symptoms resolve after stopping the ACE inhibitor or ARB.

If intestinal angioedema is diagnosed, discontinue the suspect medicine.¹¹