How to manage Angiotensin-Converting Enzyme (ACE) inhibitor-induced cough?

Management of ACE Inhibitor-Induced Cough

The most effective treatment for ACE inhibitor-induced cough is to discontinue the ACE inhibitor and switch to an angiotensin receptor blocker (ARB), which has a dramatically lower incidence of cough (similar to placebo) while maintaining equivalent cardiovascular benefits. 1

Diagnostic Confirmation

Before making any changes, confirm the ACE inhibitor is actually causing the cough:

• Discontinue the ACE inhibitor regardless of when the cough started relative to when the medication was initiated 1
• Expect cough resolution within 1-4 weeks after stopping the medication, though it may take up to 3 months in some patients 1, 2
• The diagnosis is confirmed only when the cough resolves after discontinuation 1

Primary Management Strategy: Switch to an ARB

Switching to an ARB is the Grade A recommendation when persistent or intolerable ACE inhibitor-induced cough occurs 1:

• ARBs do not inhibit ACE and therefore don't cause bradykinin accumulation, which is the mechanism behind ACE inhibitor cough 2, 3
• Cough incidence with ARBs is similar to placebo (approximately 2-3%) compared to ACE inhibitors (7.9%) 1, 4, 5
• In patients with prior ACE inhibitor-induced cough, losartan caused cough in only 20% versus 69% with lisinopril 5
• Valsartan caused cough in 19.5% versus 68.9% with lisinopril in similar patients 6

Specific ARB Recommendations

Start with losartan 25-50 mg once daily as it is the most studied ARB for this indication 3:

• Titrate to 50 mg daily if needed for blood pressure control 3
• Alternative ARBs include valsartan (starting 40 mg daily, max 80 mg) 2 or candesartan (4-8 mg daily) 3
• All ARBs have equivalent cough profiles, so choose based on dosing convenience, cost, and comorbidities rather than cough risk 3

Important Caveat About ARBs

Rare cases of ARB-induced cough have been reported 7:

• While extremely uncommon, some patients may develop cough with ARBs 7
• If cough persists after switching to an ARB, consider other causes of cough first before attributing it to the ARB 2

Alternative Approach: Rechallenge with ACE Inhibitor

If there is a compelling reason to continue ACE inhibitor therapy, consider a rechallenge after cough resolution (Grade A recommendation) 1:

• Some patients' cough may not recur upon reintroduction 1, 8
• Perindopril has the lowest incidence of cough among ACE inhibitors due to high tissue ACE affinity 8, 9
• Consider switching from one ACE inhibitor to another, as cough incidence varies within the class 9

If ACE Inhibitor Cannot Be Discontinued

When switching medications is not an option, attempt pharmacologic cough suppression (Grade B recommendation) 1:

Medications That May Attenuate Cough:

• Amlodipine or nifedipine (calcium channel blockers) have shown ability to suppress ACE inhibitor-induced cough in controlled trials 1, 2
• Sodium cromoglycate (cromolyn) 1.6 mg via MDI 4 times daily or 20 mg capsules 4 times daily has shown efficacy in case reports 1, 10
• Other options include theophylline, sulindac, indomethacin, ferrous sulfate, or picotamide 1

Important limitation: These suppressive therapies have only fair quality evidence and intermediate benefit 1

Monitoring After Switching

• Check blood pressure within 1-2 weeks after initiating ARB therapy 3
• Monitor renal function and potassium levels as ARBs can cause hyperkalemia and affect renal function similar to ACE inhibitors 3
• Watch for postural blood pressure changes, especially in elderly patients 3
• Be vigilant for angioedema in the first few weeks, as rare cases have occurred in patients who previously had angioedema with ACE inhibitors 3

What NOT to Use for Cough Suppression

Avoid codeine or pholcodine due to adverse effects and lack of superior efficacy 11:

• Dextromethorphan 60 mg is preferred if symptomatic cough relief is needed 11
• Avoid cough preparations containing sympathomimetic decongestants as they can elevate blood pressure 11