What alternative medication should be used after discontinuing Lisinopril (Angiotensin-Converting Enzyme Inhibitor) in a patient who developed angioedema?

From the Guidelines

For a patient who develops angioedema due to lisinopril, I strongly recommend switching to a non-ACE inhibitor antihypertensive medication, specifically an angiotensin II receptor blocker (ARB) such as losartan, as it is considered safe and effective, with a low risk of angioedema, as stated in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.

Alternatives to ACE Inhibitors

When considering alternatives to ACE inhibitors for a patient who has developed angioedema, several factors must be taken into account, including the patient's comorbidities, blood pressure goals, and potential interactions with other medications.

• ARBs like losartan (50-100 mg daily) are good alternatives because they work through a different mechanism that doesn't significantly affect bradykinin levels, thus posing a much lower risk of angioedema, as supported by the guideline 1.
• Calcium channel blockers such as amlodipine (2.5-10 mg daily) are also appropriate options, though they may cause dose-related pedal edema, which is more common in women than men, as noted in the guideline 1.
• Diuretics, including hydrochlorothiazide (25-50 mg daily), can be considered, especially in patients with specific conditions where diuretics are preferred, such as symptomatic heart failure or moderate-to-severe chronic kidney disease (CKD), as outlined in the guideline 1.

Rationale for Choosing Losartan

The choice of losartan as a preferred alternative is based on its efficacy, safety profile, and the fact that patients with a history of angioedema with an ACE inhibitor can receive an ARB beginning 6 weeks after the ACE inhibitor is discontinued, as recommended in the guideline 1. This approach minimizes the risk of cross-reactivity and ensures the patient's blood pressure is adequately managed without exposing them to unnecessary risks associated with ACE inhibitors.

Considerations for Other Options

While other ARBs and antihypertensive classes are available, the decision should be tailored to the individual patient's needs and medical history. For instance, valsartan and olmesartan are also viable options within the ARB class, but the choice among them should consider factors like the patient's renal function, potential drug interactions, and specific contraindications, as detailed in the guideline 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Alternatives to Lisinopril

After discontinuing lisinopril due to angioedema, alternative medications can be considered.

• Angiotensin receptor blockers (ARBs) may be used cautiously in patients who have previously experienced ACE inhibitor-related angioedema, as the risk of angioedema with ARB therapy is lower than with ACE inhibitors 2.
• The degree of ACEI-angiotensin receptor blocker angioedema cross-reactivity is difficult to determine, but multiple studies have reported relatively low rates of native angioedema with angiotensin receptor blockers (approximately half that of ACEIs, or 0.1%) and a low incidence of cross-reactivity (<10%) 3.

Treatment of Angioedema

In cases of angioedema, treatment may involve:

• Discontinuation of the medication 4, 2, 5.
• Administration of an antihistamine, such as diphenhydramine 4.
• Use of C1 esterase inhibitor (C1-INH) in severe cases, which may effectively treat angiotensin-converting enzyme inhibitor-induced angioedema (ACEi-AE) 6.
• Other interventions, such as epinephrine and maneuvers to protect the integrity of the airway, may be necessary in life-threatening cases 2, 5.