Should I discontinue lisinopril (Angiotensin-Converting Enzyme inhibitor) in a patient with a history of hypertension or heart failure who is starting spironolactone (potassium-sparing diuretic)?

Should You Discontinue Lisinopril When Starting Spironolactone?

No, you should not routinely discontinue lisinopril when starting spironolactone—instead, continue both medications with close monitoring of potassium and renal function, as the combination provides additive mortality and morbidity benefits in heart failure. 1

Rationale for Continuing Both Medications

The European Society of Cardiology guidelines explicitly recommend that spironolactone be added to optimal doses of both a beta-blocker AND an ACE inhibitor (or ARB), not as a replacement for ACE inhibitor therapy 1. The landmark trials demonstrating spironolactone's mortality benefit (RALES) enrolled patients already on ACE inhibitors, with 93-100% of patients receiving concurrent RAAS blockade 1.

The combination therapy is specifically designed to be additive:

• ACE inhibitors reduce mortality and prevent disease progression in heart failure 1
• Spironolactone provides additional mortality reduction (30% relative risk reduction in RALES) when added to ACE inhibitors 1
• Discontinuing the ACE inhibitor would eliminate its proven survival benefit 1

Critical Safety Monitoring Protocol

Before initiating spironolactone with lisinopril, verify:

• Serum potassium <5.0 mmol/L 1
• Serum creatinine <220 μmol/L (2.5 mg/dL) 1
• eGFR >30 mL/min/1.73m² 1

Monitoring schedule after starting spironolactone:

• Check potassium and creatinine at 1 week and 4 weeks after initiation 1
• Then at 1,2,3, and 6 months after achieving maintenance dose 1
• Subsequently every 6 months 1

Dosing Strategy to Minimize Hyperkalemia Risk

Start spironolactone at 25 mg once daily (not higher) when combined with ACE inhibitors 1. The FDA label explicitly warns that concomitant ACE inhibitor therapy increases hyperkalemia risk and mandates close monitoring 2.

Discontinue potassium supplementation in heart failure patients starting spironolactone 2. This is a critical step often overlooked.

Target dose is 25-50 mg daily, with most patients tolerating 25 mg 1, 3. Evidence from TOPCAT shows that even lower doses (median 20 mg/day in high-risk subgroups) maintain efficacy while reducing side effects 3.

When to Adjust or Stop Medications

If potassium rises to 5.5-6.0 mmol/L:

• Halve the spironolactone dose (e.g., 25 mg every other day) 1
• Continue lisinopril at current dose
• Recheck labs closely 1

If potassium exceeds 6.0 mmol/L:

• Stop spironolactone immediately 1
• Continue lisinopril (do not discontinue) 1
• Monitor blood chemistry closely and treat hyperkalemia 1
• Consider restarting spironolactone at lower dose once potassium normalizes 3

If creatinine rises to >220 μmol/L (2.5 mg/dL):

• Halve spironolactone dose 1
• If creatinine exceeds 310 μmol/L (3.5 mg/dL), stop spironolactone 1

High-Risk Populations Requiring Extra Vigilance

Elderly patients (≥75 years):

• Receive lower spironolactone doses in practice (median ~20 mg/day) 3
• Have 30% discontinuation rates in first year 3
• Experienced mean 45% increase in creatinine and 21% increase in potassium in real-world cohorts 4

Patients with baseline renal dysfunction (eGFR 30-60 mL/min/1.73m²):

• Required lower doses in TOPCAT (median ~20 mg/day) 3
• Monitor more frequently than standard protocol 5, 4

Additional risk factors for life-threatening hyperkalemia:

• Diabetes mellitus 5
• Dehydration risk 5
• Concurrent NSAIDs, trimethoprim, or heparin 2, 5
• Worsening heart failure 5

Common Pitfalls to Avoid

Never combine spironolactone with both an ACE inhibitor AND an ARB ("triple RAAS blockade")—guidelines explicitly state "but not an ACEI and an ARB" when adding spironolactone 1. This dramatically increases hyperkalemia risk without additional benefit.

Do not exceed 25 mg daily spironolactone in patients on ACE inhibitors with any risk factors for hyperkalemia 5. A surveillance study of 25 cases of life-threatening hyperkalemia found mean spironolactone dose was only 57 mg daily, with 12 patients requiring ICU admission and 2 deaths 5.

Spironolactone discontinuation is associated with 2-4 fold higher risk of adverse events 3, 1. If side effects occur, dose reduction is preferable to complete cessation 3.

Monitor more frequently than you think necessary—real-world studies show 36% develop hyperkalemia (>5.0 mmol/L) and 10% develop severe hyperkalemia (>6.0 mmol/L), far higher than clinical trial rates 4.