Which medication should be stopped in a patient with hyperkalemia and impaired renal function on metformin, atorvastatin, lisinopril (Angiotensin-Converting Enzyme inhibitor), and furosemide (loop diuretic) who is being treated with heparin for Deep Vein Thrombosis (DVT)?

Lisinopril Should Be Stopped

In this patient with hyperkalemia (K 6.0 mEq/L) and worsening renal function (creatinine 120 from baseline 115), lisinopril must be discontinued immediately as the ACE inhibitor is the primary cause of the hyperkalemia and poses the greatest risk for further deterioration.

Rationale for Stopping Lisinopril

Direct Mechanism of Hyperkalemia

• ACE inhibitors like lisinopril directly cause hyperkalemia by blocking the renin-angiotensin-aldosterone system, reducing aldosterone-mediated potassium excretion in the distal nephron 1, 2
• The FDA label explicitly warns that "drugs that inhibit the renin angiotensin system can cause hyperkalemia" and recommends monitoring serum potassium periodically 1
• Risk factors present in this patient include renal insufficiency (creatinine 120) and diabetes mellitus, both of which dramatically increase hyperkalemia risk with ACE inhibitors 1, 3

Severity Threshold Requiring Action

• A potassium level of 6.0 mEq/L represents moderate-to-severe hyperkalemia requiring immediate intervention 4
• The European Society of Cardiology recommends discontinuing or reducing RAAS inhibitors immediately when K+ >6.5 mEq/L, and this patient at 6.0 mEq/L is approaching that critical threshold 4
• Patients with renal insufficiency and diabetes on ACE inhibitors have up to 10% risk of developing hyperkalemia, with severe cases (K+ >6.0 mEq/L) occurring in high-risk populations 5, 2

Worsening Renal Function

• The FDA label specifically states to "consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on lisinopril" 1
• The creatinine increase from 115 to 120 μmol/L, while modest, represents deteriorating renal function that will further impair potassium excretion 1
• Patients with chronic kidney disease starting lisinopril have increased risk of hyperkalemia, particularly with declining eGFR 3

Why Other Medications Should NOT Be Stopped

Heparin (Option A)

• While heparin can cause hyperkalemia through aldosterone suppression, this effect is typically seen with prolonged use (>7 days) and is less pronounced than ACE inhibitor-induced hyperkalemia 6
• Heparin is essential for treating the acute DVT and stopping it would expose the patient to life-threatening pulmonary embolism risk 6
• The prolonged PT/APTT indicates therapeutic anticoagulation is being achieved, and discontinuation would be dangerous 6

Furosemide (Option B)

• Loop diuretics like furosemide actually reduce hyperkalemia risk by promoting urinary potassium excretion 7
• Studies show concurrent use of loop or thiazide diuretics is associated with reduced hyperkalemia risk in patients on ACE inhibitors 5
• The European Society of Cardiology recommends continuing thiazide diuretics as they promote potassium excretion and can help lower serum potassium 6
• Stopping furosemide would worsen fluid retention and potentially exacerbate hyperkalemia 8

Metformin (Option D)

• Metformin does not cause hyperkalemia and has no direct effect on potassium homeostasis 7
• The primary concern with metformin in this setting is lactic acidosis risk with worsening renal function, but the creatinine of 120 μmol/L (~1.4 mg/dL) is not yet at the threshold requiring discontinuation 7
• Stopping metformin would worsen glycemic control in this diabetic patient without addressing the hyperkalemia 7

Immediate Management Algorithm

Step 1: Discontinue Lisinopril

• Stop lisinopril immediately given K+ 6.0 mEq/L and declining renal function 1
• The American College of Cardiology recommends discontinuing ARBs/ACE inhibitors as the primary intervention in moderate hyperkalemia with Stage 3 CKD 6

Step 2: Monitor Closely

• Recheck potassium and creatinine within 24-48 hours after stopping lisinopril 4, 6
• Obtain ECG to assess for hyperkalemia-related changes (peaked T waves, widened QRS) 4

Step 3: Consider Potassium Binder if Needed

• If potassium remains >5.5 mEq/L after stopping lisinopril, initiate sodium zirconium cyclosilicate or patiromer 6
• Avoid sodium polystyrene sulfonate (Kayexalate) in elderly patients due to serious gastrointestinal adverse events 6

Step 4: Continue Essential Medications

• Continue heparin for DVT treatment with close monitoring of anticoagulation 6
• Continue furosemide as it will help promote potassium excretion 7, 5
• Continue metformin unless creatinine worsens significantly (>1.5 mg/dL or eGFR <45 mL/min) 7

Critical Pitfalls to Avoid

• Do not continue lisinopril hoping dietary restriction alone will correct hyperkalemia—ACE inhibitors are the primary driver in this clinical scenario 1, 3
• Do not stop heparin for the hyperkalemia, as this exposes the patient to potentially fatal pulmonary embolism 6
• Do not stop furosemide, as loop diuretics actually help lower potassium and stopping them may worsen both hyperkalemia and volume status 5, 8
• Do not add potassium supplements or potassium-sparing diuretics while the patient is hyperkalemic 4, 1

Long-Term Considerations

• Once potassium normalizes to 4.0-5.0 mEq/L, consider reintroducing lisinopril at a lower dose (5 mg daily) with close monitoring if blood pressure control requires it 6
• Alternative antihypertensive agents that do not affect potassium homeostasis (calcium channel blockers like amlodipine) should be considered 6
• Newer potassium binders (patiromer or sodium zirconium cyclosilicate) can enable continuation of RAAS inhibitors in patients requiring them for cardio-renal protection 7, 6