Switching from Ramipril to Losartan for ACE Inhibitor-Induced Cough
Yes, immediately switch from ramipril to losartan for sudden cough, as this is the guideline-recommended first-line alternative with a Class I, Level A recommendation from the American College of Cardiology. 1, 2
Why This Switch Is Appropriate
ACE inhibitor-induced cough is a well-documented class effect occurring in 5-35% of patients taking medications like ramipril, caused by accumulation of bradykinin and substance P when ACE is inhibited. 1 The cough is typically dry and persistent, often beginning within days to weeks after starting the medication. 3
ARBs like losartan are the preferred alternative because they do not inhibit ACE and therefore don't cause bradykinin accumulation, resulting in cough rates similar to placebo (approximately 2-3%) compared to ACE inhibitors (7.9%). 1, 3
Implementation Strategy
Immediate Steps:
- Discontinue ramipril immediately - this is the only uniformly effective treatment for ACE inhibitor-induced cough. 2
- Start losartan 25-50 mg once daily as the initial dose, with 25 mg being more appropriate for elderly patients. 1
- Cough resolution is expected within 1-4 weeks after stopping ramipril, though it may take up to 3 months in some patients. 1, 3
Monitoring Requirements:
- Check baseline renal function and potassium before starting losartan. 2
- Reassess blood pressure, renal function, and potassium within 1-2 weeks after losartan initiation. 2
- Monitor blood chemistry at 4-month intervals thereafter. 2
Dose Titration:
- If blood pressure remains ≥140/90 mm Hg after 1 month, increase losartan to 100 mg once daily. 1, 4
- The maximum recommended dose is 100 mg daily. 4
- Double the ARB dose every 2-4 weeks if blood pressure control is inadequate and the medication is well-tolerated. 2
Critical Safety Considerations
Angioedema Risk:
Although rare (<1%), angioedema can occur with ARBs in patients who previously experienced angioedema with ACE inhibitors. 2 Use caution during initial treatment, as cross-reactivity has been reported. 2 If angioedema occurs with losartan, discontinue immediately and avoid all ARBs for the patient's lifetime. 2
Acceptable Laboratory Changes:
- Creatinine increases up to 50% above baseline or 266 μmol/L (3 mg/dL), whichever is smaller, are acceptable. 2
- Potassium levels up to 5.5 mmol/L are acceptable. 2
- If potassium rises above 5.5 mmol/L, halve the ARB dose and recheck within 1-2 weeks. 2
- Seek specialist advice if potassium exceeds 6.0 mmol/L or creatinine increases by >100%. 2
Evidence Supporting This Switch
Clinical trials demonstrate that the incidence of cough with losartan therapy in patients who had cough with ACE inhibitors is similar to placebo or hydrochlorothiazide (17-29% vs. 25-35% for placebo/HCTZ, compared to 62-69% for lisinopril). 5
The CORD IA trial involving 4,016 patients switching from an ACEI to losartan showed that dry cough was 8 times more frequently reported with ramipril than losartan. 4 The switch was safe and effective, with significant blood pressure reduction and no increase in adverse events. 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 ramipril. 2
- Do not combine ARBs with both ACE inhibitors and aldosterone antagonists - this increases the risk of hyperkalemia and renal dysfunction. 2
- Do not abruptly withdraw without starting the ARB - clinical deterioration is likely with abrupt withdrawal of renin-angiotensin system inhibition. 2
- Avoid concomitant nephrotoxic drugs (NSAIDs) during the transition period. 2
Rare Exception
While extremely rare, one case report described losartan-induced cough that resolved with enalapril. 6 However, this represents an isolated case in a 23-year-old ACE inhibitor-naive patient and should not influence standard practice, as the overwhelming evidence supports ARBs having dramatically lower cough rates than ACE inhibitors. 1, 5, 4