What antihypertensive should I switch my patient to who is experiencing a dry cough on an ACE inhibitor?

Switch to an Angiotensin Receptor Blocker (ARB)

For a patient experiencing dry cough on an ACE inhibitor, switch immediately to an angiotensin receptor blocker (ARB), which provides equivalent cardiovascular benefits without causing bradykinin accumulation—the mechanism responsible for ACE inhibitor-induced cough. 1

Immediate Action Required

• Discontinue the ACE inhibitor immediately, as this is the only uniformly effective treatment for ACE inhibitor-induced cough 2, 3, 4
• Start an ARB without any washout period—no overlap or gap between medications is necessary 4
• Expect cough resolution within 1-4 weeks after stopping the ACE inhibitor, though it may persist up to 3 months in some patients 2, 3, 4

Specific ARB Recommendations and Dosing

First-Line Choice: Losartan

• Start losartan 25-50 mg once daily 2
• Titrate to 100 mg once daily if blood pressure remains ≥140/90 mm Hg and the medication is well-tolerated 4
• Clinical trial evidence: Losartan showed cough incidence of 17-29% versus 62-69% with lisinopril in patients with prior ACE inhibitor-induced cough—rates similar to placebo (35%) or hydrochlorothiazide (25%) 5

Alternative Options

• Candesartan 8 mg once daily, titrate to 32 mg once daily 4
• Valsartan 40 mg twice daily (or 80 mg once daily), titrate to 160 mg twice daily 4, 6
• All ARBs have equivalent cough profiles (2-3% incidence, similar to placebo), so selection should be based on dosing convenience, comorbidities, and cost 2

Essential Monitoring Protocol

Baseline Assessment (Before Starting ARB)

• Check serum creatinine and potassium before initiating ARB therapy 4

Early Follow-up (1-2 Weeks)

• Recheck blood pressure, renal function, and potassium within 1-2 weeks of ARB initiation 2, 4

Acceptable Laboratory Changes

• Creatinine increase up to 50% above baseline or 266 μmol/L (3 mg/dL), whichever is lower, is acceptable 4
• Potassium up to 5.5 mmol/L is acceptable 4
• If potassium rises above 5.5 mmol/L, halve the ARB dose and recheck within 1-2 weeks 4
• If potassium exceeds 6.0 mmol/L or creatinine increases >100%, seek specialist advice 4

Long-term Monitoring

• Repeat blood chemistry every 4 months after stabilization 4

Dose Titration Strategy

• Double the ARB dose every 2-4 weeks if blood pressure remains ≥140/90 mm Hg and the medication is well-tolerated 4
• Target evidence-based maximum doses shown to reduce cardiovascular events in clinical trials 1, 4
• Accept intermediate doses if target doses are not tolerated—some ARB therapy is better than none 1, 4

Critical Safety Warnings

Angioedema Risk

• Although rare (<1%), angioedema can occur with ARBs in patients who previously experienced ACE inhibitor-induced angioedema 1, 4
• Counsel patients to report any lip, tongue, or throat swelling immediately 4
• If angioedema occurs with an ARB, discontinue immediately and avoid all ARBs for the patient's lifetime 4

Blood Pressure Management

• Asymptomatic hypotension does not require dose adjustment 4
• Symptomatic hypotension requires: reconsideration of other vasodilators and reduction of diuretic dose if no signs of congestion 4

Common Pitfalls to Avoid

• Do not assume all cough is ACE inhibitor-related—exclude pulmonary edema and other respiratory causes before attributing cough to the ACE inhibitor 4
• Do not combine ARBs with both ACE inhibitors and aldosterone antagonists—this increases risk of hyperkalemia and renal dysfunction (Class III: Harm recommendation) 1, 4
• Do not abruptly withdraw renin-angiotensin system inhibition—clinical deterioration is likely; seek specialist advice before treatment discontinuation 4
• Do not stop concomitant nephrotoxic drugs (NSAIDs) or potassium supplements without first assessing for signs of congestion 4

Special Considerations for Heart Failure Patients

• If the patient has heart failure with reduced ejection fraction (HFrEF), ARBs are Class I, Level A recommendation for ACE inhibitor-intolerant patients 1
• Consider ARNI (sacubitril-valsartan) instead of standard ARB if patient has symptomatic HFrEF NYHA class II-III, as it provides superior mortality and morbidity reduction compared to ACE inhibitors 1
• ARNI should not be administered within 36 hours of the last ACE inhibitor dose due to angioedema risk 1
• ARNI is contraindicated in patients with any history of angioedema 1

Evidence Quality

The recommendation to switch to an ARB for ACE inhibitor-induced cough is supported by:

• Class I, Level A evidence from ACC/AHA/HFSA guidelines 1
• FDA-approved labeling demonstrating significantly lower cough rates with ARBs (2.6% with valsartan, 17-29% with losartan) versus ACE inhibitors (68-69% with lisinopril) 5, 6
• Randomized controlled trials specifically designed to assess cough in ACE inhibitor-intolerant patients 5, 7