What alternative antihypertensive medication can replace lisinopril (Angiotensin-Converting Enzyme Inhibitor) in an adult patient with hypertension or heart failure who experiences a cough while taking lisinopril 40 mg?

Replacement for Lisinopril-Induced Cough

Switch to an angiotensin receptor blocker (ARB) such as losartan, valsartan, or candesartan, as ARBs have a cough incidence similar to placebo and are the recommended alternative when ACE inhibitor cough is intolerable. 1

Clinical Approach to ACE Inhibitor-Induced Cough

First: Confirm the Diagnosis

Before switching medications, you must confirm that lisinopril is actually causing the cough, not other conditions: 1

• Exclude pulmonary edema - ACE inhibitor cough is dry and persistent, not productive with signs of fluid overload 1
• Rule out smoking-related lung disease - particularly relevant in patients with heart failure who may have concurrent COPD 1
• Discontinue lisinopril regardless of timing - even if cough started months after initiation, stop the drug to confirm causation 1
• Wait for resolution - cough typically resolves within 1-4 weeks of stopping, though may take up to 3 months in some patients 1

Second: Determine if ACE Inhibitor is Essential

The decision to switch depends on your patient's underlying condition:

For Heart Failure patients: 1

• ACE inhibitor-induced cough rarely requires treatment discontinuation in heart failure 1
• Only switch if cough is very troublesome (e.g., preventing sleep) and proven due to ACE inhibition through withdrawal and rechallenge 1
• Clinical deterioration is likely if ACE inhibitor is withdrawn in heart failure patients 1
• Consider specialist advice before discontinuation 1

For Hypertension-only patients: 1

• Switching is more straightforward as multiple effective alternatives exist
• No mortality benefit lost by switching drug classes

Recommended Replacement: Angiotensin Receptor Blockers (ARBs)

ARBs are the evidence-based first choice for replacing lisinopril when cough occurs: 1

Why ARBs Work Without Causing Cough

• ARBs do not inhibit ACE, so they don't cause accumulation of bradykinin and substance P (the mechanism behind ACE inhibitor cough) 1
• Cough incidence with ARBs is similar to placebo or hydrochlorothiazide 1, 2
• In patients with prior ACE inhibitor cough, losartan caused cough in only 17-29% versus 62-69% with lisinopril 2

Specific ARB Options

Losartan is the most studied for this indication: 2

• Start 50 mg once daily for hypertension
• Can titrate to 100 mg once daily if needed
• FDA label specifically documents low cough rates in patients with prior ACE inhibitor cough 2

Other ARBs (valsartan, candesartan, irbesartan, telmisartan) are equally appropriate alternatives 1

Important Caveat About ARBs

While rare, ARBs can occasionally cause cough through mechanisms independent of ACE inhibition: 3, 4

• One case report documented losartan-induced cough that resolved when switched back to enalapril 3
• In observational studies, carry-over effects from prior ACE inhibitor use accounted for most cough reports with ARBs 4
• True ARB-induced cough appears extremely uncommon 4

Alternative Options if ARB is Not Suitable

If an ARB cannot be used (e.g., contraindication, cost, or rare ARB-induced cough), consider: 1

For Hypertension:

• Calcium channel blockers (amlodipine, nifedipine)
• Thiazide or thiazide-like diuretics
• Beta-blockers
• These do not provide the same renal and cardiac protection as ACE inhibitors/ARBs in certain conditions 1

For Heart Failure:

• ARB remains strongly preferred over other classes 1
• Seek specialist advice if ARB also not tolerated 1

If Patient Insists on Continuing ACE Inhibitor

Some patients may have compelling reasons to continue ACE inhibitor therapy despite cough: 1

Cough suppression strategies (fair evidence, intermediate benefit): 1

• Sodium cromoglycate
• Theophylline
• NSAIDs (sulindac, indomethacin)
• Calcium channel blockers (amlodipine, nifedipine)
• Ferrous sulfate
• Picotamide

However, discontinuation is the only uniformly effective treatment for ACE inhibitor cough 1

Dosing Equivalency Considerations

When switching from lisinopril 40 mg to an ARB: 1

• Lisinopril 40 mg is above the typical target dose (30-35 mg daily) 1
• Start ARB at standard initial dose, then titrate to achieve same blood pressure control
• Monitor blood pressure closely during transition