What is a suitable replacement medication for a patient taking lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor), considering potential comorbidities such as impaired renal function?

Replacement for Lisinopril

Angiotensin receptor blockers (ARBs) are the preferred replacement for lisinopril when ACE inhibitor discontinuation is necessary, particularly in patients who develop intolerable cough or angioedema. 1

Primary Replacement Options

ARBs as First-Line Alternatives

• Candesartan or valsartan are the most strongly recommended ARB alternatives, as they have demonstrated equivalent mortality and morbidity benefits to ACE inhibitors in heart failure with reduced ejection fraction 1
• Losartan showed no significant difference compared to captopril in terms of mortality or clinical deterioration in heart failure patients 2
• ARBs provide similar hemodynamic effects to ACE inhibitors but with a significantly lower incidence of cough (approximately one less case of angioedema per 500 patients) 2

When to Choose ARBs

• Use ARBs when patients develop ACE inhibitor-induced cough that is severe enough to disrupt sleep or daily activities 1
• ARBs are the definitive choice when angioedema occurs with ACE inhibitors, as this is a contraindication to further ACE inhibitor use 1
• In patients with heart failure who cannot tolerate ACE inhibitors due to adverse effects, candesartan reduces hospitalizations by 3 per 100 patients per year, though it carries similar risks of renal dysfunction and hyperkalemia 2

Critical Considerations for Renal Impairment

Monitoring Requirements

• Monitor serum creatinine and potassium 7-14 days after initiating ARB therapy and after each dose change 1
• An increase in creatinine up to 50% above baseline or to 3 mg/dL (266 μmol/L), whichever is greater, is acceptable 1
• If potassium rises to ≥6.0 mmol/L or creatinine increases by 100% or above 4 mg/dL (354 μmol/L), seek specialist advice 1

Renal Function Thresholds

• ARBs can be continued with eGFR ≥30 mL/min/1.73 m² without dose adjustment in most cases 1
• In patients with eGFR <30 mL/min/1.73 m², use ARBs with extreme caution and increase monitoring frequency 1
• ARBs should be avoided in bilateral renal artery stenosis or unilateral stenosis in a solitary kidney, as they cause the same negative renal effects as ACE inhibitors 3

Important Contraindications and Warnings

Absolute Contraindications

• Never combine ACE inhibitors with ARBs, as this increases adverse events including hyperkalemia, syncope, and acute kidney injury without added cardiovascular benefit 1
• Do not use ARBs with direct renin inhibitors (aliskiren), particularly in patients with renal insufficiency or diabetes mellitus 1
• ARBs are contraindicated in pregnancy and should be avoided in sexually active individuals of childbearing potential not using reliable contraception 1

Relative Contraindications

• Avoid ARBs when serum creatinine is ≥2.5 mg/dL in men or ≥2.0 mg/dL in women, or when serum potassium is ≥5.0 mEq/L 1
• Use with extreme caution in patients with severe volume depletion or hypotension 1

Alternative Medication Classes

When ARBs Are Not Suitable

• Thiazide-like diuretics (chlorthalidone, indapamide) are preferred alternatives for blood pressure control when both ACE inhibitors and ARBs are contraindicated 1
• Dihydropyridine calcium channel blockers are effective for blood pressure reduction but lack the renoprotective benefits of ACE inhibitors/ARBs in patients with albuminuria 1
• Beta-blockers (carvedilol, metoprolol succinate, bisoprolol) should be continued for heart failure but are less effective for stroke prevention than diuretics or calcium channel blockers 1

Special Populations

• In African American patients with NYHA class III-IV heart failure, add hydralazine plus isosorbide dinitrate to the regimen (but hydralazine without a nitrate should be avoided) 1
• For patients with heart failure and preserved ejection fraction, beta-blockers, ARBs, or calcium channel blockers may minimize symptoms, though evidence is limited 1

Common Pitfalls to Avoid

• Do not assume ARBs are safer than ACE inhibitors regarding renal dysfunction—both classes share risks of hyperkalemia, renal failure, and hypotension 2
• Avoid discontinuing concomitant nephrotoxic drugs (NSAIDs, potassium supplements) before attributing renal dysfunction solely to the ARB 1
• Do not stop ARB therapy abruptly without specialist consultation if renal dysfunction develops, as clinical deterioration is likely 1
• Ensure adequate volume status before initiating ARB therapy, as volume depletion significantly increases the risk of acute renal failure 1