Published: 1 June 2023

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Reminder: ACE inhibitor-induced angioedema can be fatal

Published: 1 June 2023
Prescriber Update 44(2): 29–30
June 2023

The Centre for Adverse Reactions Monitoring (CARM) recently received a report of fatal angioedema with an ACE inhibitor. The patient had experienced minor tongue swelling with an ACE inhibitor previously. A different ACE inhibitor was started at a later date, and the patient developed angioedema with a fatal outcome.

Medsafe is reminding health professionals about the risk of angioedema with ACE inhibitors and the importance of taking an adverse reaction and allergy history before starting any medicine.

ACE inhibitors

Angiotensin-converting enzyme inhibitors (ACE inhibitors) inhibit the conversion of angiotensin I to angiotensin II.¹ They have many indications, such as treatment of hypertension, myocardial infarction, heart failure and diabetic nephropathy.

ACE inhibitors approved in New Zealand include captopril, cilazapril, enalapril, lisinopril, perindopril, quinapril and ramipril.

ACE inhibitor-induced angioedema

Angioedema is a sudden localised swelling of the skin or mucous membranes without itching or urticaria. ACE inhibitor-induced angioedema often manifests as swelling of the face, lips or tongue. Rarely, airway involvement causes asphyxiation which can be fatal. Gastrointestinal symptoms associated with visceral angioedema can also occur.²

Angioedema is thought to occur in around 0.1% to 0.7% of patients who take an ACE inhibitor.² Onset is usually during the first weeks or months of therapy, but it can occur years into treatment.³ Angioedema has also been reported with angiotensin II receptor blockers (ARBs; eg, candesartan, losartan), but the risk is thought to be lower than with ACE inhibitors.⁴

Management

If a patient taking an ACE inhibitor presents with signs of angioedema, consider ACE inhibitors as the cause and stop the medicine.

Clinical management of ACE-induced angioedema includes supportive care and monitoring, and airway management if the mouth or throat is involved.² Some patients experience repeated episodes even after stopping the ACE inhibitor. Counsel patients to seek immediate medical attention if angioedema recurs.

If ACE inhibitors are continued after an initial episode of angioedema, further episodes may occur that are more severe and life-threatening. ACE inhibitors are contraindicated in patients with a history of ACE inhibitor-induced angioedema. If clinically indicated, switch the patient to an alternative therapy as per local guidelines.^2,4

Advice to health professionals

Before prescribing an ACE inhibitor, ask patients if they have taken these medicines before and if they had any adverse reactions. Specifically ask about swelling.

Inform patients who are starting ACE inhibitors about the symptoms of angioedema and advise them to seek urgent medical attention if these occur.

ACE inhibitors should not be prescribed to patients with a history of ACE inhibitor-induced angioedema. Educate patients who have experienced ACE inhibitor-induced angioedema about the need to avoid all ACE inhibitors in the future.^2,4

Please report cases of ACE inhibitor-induced angiodema to CARM, so an appropriate alert can be added to the national Medical Warning System.

New Zealand case reports

As of 22 March 2023, CARM had received 479 reports of angioedema where the causal medicine was an ACE inhibitor, including 3 fatal reports.

More information

• Prescriber Update March 2021: Vildagliptin and ACE inhibitors – increased risk of angioedema
• bpac^nz March 2021: Prescribing ACE inhibitors: time to reconsider old habits
• Search for a data sheet
• Prescriber Update June 2020: Alerting the Medical Warning System can save lives!

References

1. New Zealand Formulary (NZF). 2023. NZF v131: Angiotensin-converting enzyme inhibitors 1 May 2023. URL: nzf.org.nz/nzf_1242 (accessed 3 May 2023).
2. Guyer A and Banerji A. 2023. ACE inhibitor-induced angioedema. In: UpToDate 10 March 2023. URL: uptodate.com/contents/ace-inhibitor-induced-angioedema (accessed 16 March 2023).
3. Makani H, Messerli FH, Romero J, et al. 2012. Meta-analysis of randomized trials of angioedema as an adverse event of renin–angiotensin system inhibitors. The American Journal of Cardiology 110(3): 383-91. DOI: 10.1016/j.amjcard.2012.03.034 (accessed 16 March 2023).
4. bpac^nz. 2021. Prescribing ACE inhibitors: time to reconsider old habits updated 25 November 2022. URL: bpac.org.nz/2021/ace.aspx (accessed 16 March 2023).