Can Angiotensin-Converting Enzyme (ACE) inhibitors cause angioedema after one year of therapy?

From the Guidelines

Yes, it is possible to develop angioedema from an ACE inhibitor even after being on therapy for a year or longer. ACE inhibitor-induced angioedema can occur at any time during treatment, with some cases reported after years of uneventful use, as noted in a study published in the Journal of Allergy and Clinical Immunology 1. This delayed reaction occurs because ACE inhibitors like lisinopril, enalapril, and ramipril block the breakdown of bradykinin, leading to its accumulation. When bradykinin levels suddenly reach a critical threshold, they can trigger blood vessel dilation and increased permeability, resulting in the characteristic swelling of angioedema.

Key Points to Consider

• Angioedema associated with ACE-I therapy frequently occurs within the first few months of therapy but can occur even after years of continuous therapy, as stated in the study 1.
• Patients experiencing angioedema secondary to one ACE-I will typically have angioedema to another ACE-I, which is consistent with this as a class effect and not a hypersensitivity reaction, as noted in the study 1.
• African American subjects are at a substantially higher risk of experiencing ACE-I–induced angioedema than white subjects, according to the study 1.
• Other factors that increase the risk of angioedema from ACE-Is include a history of smoking, increasing age, and female sex, as mentioned in the study 1.

Management and Prevention

• If you develop unexplained swelling of the face, lips, tongue, throat, extremities, or intestines while on an ACE inhibitor, seek immediate medical attention, especially if breathing or swallowing is affected.
• The management typically involves discontinuing the ACE inhibitor permanently and switching to an alternative medication class such as angiotensin receptor blockers (ARBs), calcium channel blockers, or thiazide diuretics, as recommended in the study 1.
• Once a patient experiences ACE inhibitor-induced angioedema, they should never be rechallenged with any medication from this class due to the risk of more severe reactions, as stated in the study 1.

From the Research

Angioedema and ACE Inhibitors

• Angioedema is a complication that has been reported in up to 1.0% of individuals taking angiotensin-converting enzyme inhibitors (ACE-Is) 2.
• The onset of angioedema can occur anywhere from hours to several years after initiation of therapy with ACE-Is 2, 3.
• A case study reported a life-threatening ACE inhibitor-induced angioedema after eleven years on lisinopril, highlighting the possibility of late onset angioedema 3.

Risk of Angioedema After Long-Term Therapy

• Although most cases of ACE-I-induced angioedema occur early in therapy, episodes can occur late in therapy, even after several years 2, 3.
• The risk of angioedema recurrence is higher with continued ACE-I use, with an adjusted hazard ratio of 1.45 (95% CI, 1.19 to 1.78) 4.
• Patients with a history of ACE-I-induced angioedema should not be re-challenged with this class of agents, as there is a relatively high risk of recurrence 5.

Implications for Patients on Long-Term ACE-I Therapy

• Patients on long-term ACE-I therapy should be aware of the potential risk of angioedema, even after several years of treatment 2, 3.
• Any patient with suspected ACE-I-induced angioedema should immediately discontinue the medication 2.
• Alternative treatments, such as angiotensin II receptor blockers, may be considered for patients with a history of ACE-I-induced angioedema, as they have been shown to be safe in these patients 4.