Which of the following medications: Glipizide, Atorvastatin, Lisinopril, Aspirin, Farxiga (Dapagliflozin) is most likely to cause edema?

Lisinopril is Most Likely to Cause Edema Among the Listed Medications

Among Glipizide, Atorvastatin, Lisinopril, Aspirin, and Farxiga (Dapagliflozin), lisinopril is most likely to cause edema, specifically angioedema, which can be life-threatening.

Mechanism of ACE Inhibitor-Induced Edema

• Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, can cause angioedema through inhibition of bradykinin degradation, leading to increased bradykinin levels that directly or indirectly cause angioedema 1
• This adverse effect can occur at any time during treatment, from within hours of initiation to years after starting therapy 2
• ACE inhibitor-associated angioedema occurs in approximately 0.1% to 0.7% of patients, with higher risk in African Americans, smokers, older patients, and females 3

Clinical Presentation of Lisinopril-Induced Edema

• Lisinopril-induced angioedema typically presents as asymmetric non-pitting edema affecting the face, lips, tongue, and mucous membranes 4
• It can also present as isolated laryngeal edema without facial involvement, which can be particularly dangerous and potentially fatal 2
• The onset can be rapid and may require emergency intervention, including intubation in severe cases 2

Risk Factors and Timing

• While many cases occur within the first months of therapy, angioedema can develop even after years of stable ACE inhibitor use 2
• A case report documented angioedema developing after 10 years of lisinopril therapy 2
• Another case reported angioedema developing four years after starting lisinopril/hydrochlorothiazide 4

Comparison with Other Listed Medications

• Glipizide (sulfonylurea): Not associated with significant edema as an adverse effect 1
• Atorvastatin (statin): Not known to cause significant edema 1
• Aspirin (NSAID): Can cause fluid retention and edema, but at much lower rates than ACE inhibitors 1
• Farxiga (Dapagliflozin, SGLT2 inhibitor): Actually reduces fluid retention and can help manage edema 1

Management of ACE Inhibitor-Induced Angioedema

• Immediate discontinuation of the ACE inhibitor is essential 5
• Treatment may include antihistamines, corticosteroids, epinephrine, and in severe cases, airway management 4
• Alternative antihypertensive medications should be considered, though caution is needed when switching to ARBs 3

Important Considerations When Switching Medications

• If switching from an ACE inhibitor to an ARB due to angioedema, there is a 2-17% risk of recurrent angioedema 3
• ARBs should be used with "extreme caution" in patients with a history of ACE inhibitor-induced angioedema 3
• If an ARB is necessary, start at the lowest possible dose and titrate slowly 3

Special Warnings

• Angioedema from ACE inhibitors like lisinopril can be life-threatening, especially when it affects the larynx 4
• Delayed recognition and treatment can lead to fatal outcomes due to airway obstruction 4
• Patients should be educated about early signs of angioedema and provided with an emergency action plan 3