In an 81‑year‑old man who recently started lisinopril 20 mg daily and now presents with bilateral lower‑extremity edema, mild normocytic anemia, low‑normal calcium, normal renal function, and a modestly elevated monocyte count, what is the most likely cause of the edema and what is the appropriate management?

Bilateral Edema in an 81-Year-Old on Lisinopril: Cause and Management

Most Likely Cause

The bilateral lower-extremity edema in this patient is almost certainly NOT caused by lisinopril, because ACE inhibitors do not cause bilateral dependent edema. Instead, this presentation suggests either underlying heart failure, venous insufficiency, hypoalbuminemia, or another systemic cause that requires further evaluation 1.

Why Lisinopril is Not the Culprit

• ACE inhibitors like lisinopril do not cause bilateral dependent edema through sodium retention or volume overload mechanisms 2.
• The FDA label for lisinopril lists angioedema (face, extremities, lips, tongue, glottis, larynx, or intestinal) as a serious adverse effect, but does not describe bilateral lower-extremity edema as a typical side effect 1.
• Lisinopril actually has natriuretic properties and maintains or increases renal blood flow, making fluid retention physiologically unlikely 3, 4.
• This patient's normal renal function (eGFR 71 mL/min/1.73 m², creatinine 1.05 mg/dL) and normal potassium (4.4 mmol/L) indicate the ACE inhibitor is being well tolerated without adverse hemodynamic effects 5.

Evaluate for the True Underlying Cause

Assess for Heart Failure

• Check NT-proBNP or BNP to screen for heart failure, which is the most common cause of bilateral edema in elderly patients on antihypertensive therapy 2.
• Obtain transthoracic echocardiography to assess left ventricular ejection fraction, diastolic function, and valvular disease 2.
• Examine for jugular venous distension, S3 gallop, pulmonary rales, and hepatojugular reflux as clinical markers of volume overload 2.

Rule Out Other Systemic Causes

• The mild normocytic anemia (hemoglobin 11.5 g/dL, hematocrit 36.7%) is common in elderly patients and may reflect anemia of chronic disease, but does not explain edema 6.
• The low-normal calcium (8.4 mg/dL) and low-normal albumin (3.7 g/dL) are borderline but unlikely to cause significant edema unless albumin drops below 3.0 g/dL 2.
• The modestly elevated absolute monocyte count (1.1 × 10³/µL) is nonspecific and does not suggest an acute inflammatory or infectious process driving edema 6.
• Consider venous insufficiency, lymphedema, or medication effects from other drugs (though none are listed in this case) 2.

Appropriate Management Strategy

Continue Lisinopril

• Do not discontinue lisinopril based on the presence of bilateral edema, as this is not a recognized adverse effect of ACE inhibitors and stopping proven guideline-directed therapy would harm the patient 2, 7.
• Lisinopril 20 mg daily is within the recommended target dose range (20–40 mg daily) for hypertension and heart failure, and this patient's blood pressure and renal function support continuation 7.
• Monitor renal function and potassium within 1–2 weeks, then periodically, especially if diuretics are added 7, 8, 1.

Initiate Diuretic Therapy if Heart Failure is Confirmed

• If NT-proBNP is elevated and echocardiography confirms heart failure, start a loop diuretic such as furosemide 20–40 mg daily or torsemide 10–20 mg daily 2, 8.
• Titrate the diuretic dose based on clinical response (resolution of edema, weight loss, improved dyspnea) rather than creatinine changes, as modest creatinine rises during decongestion reflect hemodynamic adjustment, not kidney injury 2, 8.
• An increase in creatinine up to 30% from baseline is acceptable when optimizing heart failure therapy with ACE inhibitors and diuretics, provided the patient is clinically improving 8.

Add SGLT2 Inhibitor if Heart Failure with Reduced or Mildly Reduced Ejection Fraction

• If ejection fraction is ≤50%, add dapagliflozin 10 mg daily or empagliflozin 10 mg daily to reduce cardiovascular and renal events, improve diuresis, and lower hyperkalemia risk 2, 8.
• SGLT2 inhibitors provide additive benefit to ACE inhibitors and should be continued even if creatinine rises modestly, as they protect kidney function long-term 2, 8.

Optimize Other Guideline-Directed Medical Therapy

• Add a beta-blocker (e.g., carvedilol, metoprolol succinate, bisoprolol) if heart failure is confirmed and the patient is not already on one 2.
• Consider a mineralocorticoid receptor antagonist (spironolactone 12.5–25 mg daily or eplerenone) if ejection fraction is reduced and potassium remains <5.0 mmol/L 2.

Common Pitfalls to Avoid

• Do not attribute bilateral dependent edema to lisinopril, as ACE inhibitors do not cause this; always search for the true underlying cause 2, 1.
• Do not stop lisinopril reflexively if creatinine rises modestly during diuretic initiation, as this represents hemodynamic adjustment and deprives the patient of proven mortality benefit 8.
• Do not delay echocardiography and natriuretic peptide testing in an elderly patient with new bilateral edema, as undiagnosed heart failure carries high morbidity and mortality 2.
• Do not use NSAIDs for any concurrent pain or inflammation, as they antagonize ACE inhibitors, promote sodium retention, and worsen renal function 9, 8.
• Do not overlook angioedema if the patient develops facial, tongue, or throat swelling, as this is a life-threatening complication requiring immediate lisinopril discontinuation and emergency treatment 1, 10.