Can a patient taking lisinopril (angiotensin-converting enzyme inhibitor) for several years still develop angioedema?

Angioedema Risk with Long-term Lisinopril Use

Yes, patients taking lisinopril can develop angioedema at any time during treatment, even after several years of use without previous complications. This life-threatening reaction can occur suddenly and without warning, regardless of how long the patient has been on the medication 1.

Angioedema Risk with ACE Inhibitors

Angioedema is a well-documented adverse effect of ACE inhibitors like lisinopril:

• Occurs in fewer than 1% of patients taking ACE inhibitors 2
• More frequent in Black patients 2
• Can develop at any time during treatment 1
• Can be life-threatening, particularly when involving the tongue, glottis, or larynx 1
• May lead to airway obstruction requiring emergency intervention 1

Clinical Presentation and Management

Angioedema associated with lisinopril typically presents as:

• Swelling of face, extremities, lips, tongue, glottis and/or larynx 1
• Possible intestinal angioedema (abdominal pain with or without nausea/vomiting) 1
• Rapid progression that may lead to airway compromise 3

If angioedema develops:

1. Immediately discontinue lisinopril 1
2. Provide appropriate therapy and monitoring until complete resolution of symptoms 1
3. Never restart any ACE inhibitor - the clinical suspicion of angioedema justifies subsequent avoidance of all ACE inhibitors for the lifetime of the patient 2

Risk Factors and Considerations

Patients may be at increased risk for angioedema while on lisinopril if they:

• Are taking concomitant mTOR inhibitors (e.g., temsirolimus, sirolimus, everolimus) 1
• Are taking neprilysin inhibitors 1
• Have a history of angioedema (unrelated to ACE inhibitor therapy) 1
• Are Black (higher rate of angioedema than in non-Black patients) 1

Alternative Medications

For patients who develop angioedema with lisinopril:

• Angiotensin receptor blockers (ARBs) may be considered as alternative therapy 2
• However, extreme caution is advised when substituting an ARB, as some patients have also developed angioedema with ARBs 2
• A waiting period of at least 6 weeks after discontinuing the ACE inhibitor is recommended before starting an ARB 2

Important Caveats

1. The onset of angioedema is unpredictable and can occur after years of uneventful treatment
2. Angioedema can be fatal if not promptly recognized and treated 4, 3
3. Emergency measures to secure the airway may be necessary in severe cases
4. Even with appropriate treatment, angioedema can progress to complete airway obstruction 4

Monitoring patients on long-term lisinopril therapy should include education about the potential signs and symptoms of angioedema, with instructions to seek immediate medical attention if they experience unexplained shortness of breath or swelling of the throat, tongue, or face.