What is the best alternative medication and dosage for a patient with a cough due to lisinopril (Angiotensin-Converting Enzyme Inhibitor - ACEI)?

Management of Lisinopril-Induced Cough

For patients with cough due to lisinopril, an angiotensin receptor blocker (ARB) such as valsartan 20-40 mg twice daily (maximum 160 mg twice daily) is the best alternative medication. 1

Confirmation of ACEI-Induced Cough

Before switching medications, confirm that the cough is indeed caused by lisinopril:

• Characteristic features: dry, persistent, nonproductive cough with an annoying "tickle" in the throat
• Typically appears within the first months of therapy
• Disappears within 1-2 weeks after discontinuation
• Recurs within days of rechallenge with another ACEI 2

Rule out other causes of cough, particularly pulmonary congestion, before attributing it to the ACEI 2, 1.

Best Alternative Medication Options

First-Line Alternative: Angiotensin Receptor Blockers (ARBs)

ARBs provide similar cardiovascular benefits to ACEIs but with significantly lower incidence of cough:

• Valsartan: 20-40 mg twice daily initially, maximum 160 mg twice daily 2, 1
• Losartan: 25-50 mg once daily initially, maximum 50-100 mg once daily 2, 1
• Candesartan: 4-8 mg once daily initially, maximum 32 mg once daily 2, 1

Evidence Supporting ARBs for ACEI-Induced Cough

1. Clinical trials show the incidence of cough is significantly lower with ARBs (17-29%) compared to ACEIs (62-69%) 1

2. In a double-blind study of patients with a history of ACEI-induced cough, the incidence of cough was:

   • Valsartan: 19.5%
   • Lisinopril: 68.9%
   • Hydrochlorothiazide: 19.0% 3

3. FDA labeling for valsartan confirms that in trials comparing valsartan to an ACEI with or without placebo, the incidence of dry cough was significantly greater in the ACEI group (7.9%) than in groups receiving valsartan (2.6%) or placebo (1.5%) 4

Monitoring After Switching to an ARB

1. Check renal function and potassium levels 1-2 weeks after initiating ARB treatment 1
2. Monitor blood pressure to ensure adequate control 1
3. Schedule follow-up every 3-6 months 1

Important Considerations and Precautions

• ARBs can cause hypotension, worsening renal function, and hyperkalemia similar to ACEIs 2
• If using ARBs with aldosterone antagonists (e.g., spironolactone), monitor potassium levels closely 1
• While rare, angioedema can occur with ARBs, so use extreme caution if the patient has a history of ACEI-induced angioedema 2
• Do not combine ARBs with ACEIs as this increases cardiovascular and renal risk without additional benefit 1

Special Situations

If there is a compelling reason to continue ACEI therapy despite cough, consider:

• Sodium cromoglycate
• Theophylline
• Amlodipine
• Nifedipine 1

However, these approaches to suppress cough while continuing ACEIs are generally not recommended unless there is an absolute indication for ACEI therapy 1.

Rare Cases

While extremely uncommon, there have been isolated reports of cough with ARBs (e.g., losartan) that resolved after switching to an ACEI 5. If cough persists after switching to an ARB, consider other antihypertensive classes.