What is the next treatment option for a patient with a minor cough who is being treated for hypertension with an Angiotensin-Converting Enzyme (ACE) inhibitor, such as lisinopril?

Management of ACE Inhibitor-Induced Cough in Hypertension

For patients experiencing a minor cough while on an ACE inhibitor for hypertension, the next treatment option is to switch to an angiotensin receptor blocker (ARB), which has a significantly lower incidence of cough while maintaining similar antihypertensive efficacy. 1

Understanding ACE Inhibitor-Induced Cough

ACE inhibitor-induced cough is a well-documented class effect occurring in 5-35% of patients taking these medications 2. This cough is typically:

• Dry and non-productive
• Associated with a tickling or scratching sensation in the throat
• More common in women, non-smokers, and persons of Chinese origin
• Not dose-dependent
• May develop within hours of the first dose or be delayed for weeks to months

Treatment Algorithm

1. Confirm ACE inhibitor as the cause

   • Discontinue the ACE inhibitor regardless of the temporal relationship between cough onset and medication initiation
   • Cough typically resolves within 1-4 weeks after discontinuation, though may take up to 3 months in some cases 2

2. Switch to an ARB

   • ARBs have a significantly lower incidence of cough compared to ACE inhibitors 1
   • Clinical trials demonstrate that the incidence of cough with ARBs is similar to that of placebo or hydrochlorothiazide 3, 4
   • In patients with a history of ACE inhibitor-induced cough, losartan showed a cough incidence of only 17% compared to 69% with lisinopril 5

3. If ARB is not tolerated or contraindicated, consider alternative antihypertensive classes:

   • Calcium channel blockers
   • Thiazide diuretics
   • Beta-blockers

Evidence Strength and Considerations

The recommendation to switch to an ARB is strongly supported by multiple clinical trials. The Losartan Cough Study Group found that in patients with a history of ACE inhibitor-related cough, the incidence of cough with losartan was significantly lower than with lisinopril and similar to hydrochlorothiazide 3. Similarly, the Telmisartan Cough Study Group reported cough incidence with telmisartan (15.6%) was comparable to placebo (9.7%) and significantly less than with lisinopril (60%) 4.

Important Caveats

1. Rare ARB-induced cough: While uncommon, ARBs can occasionally cause cough, as documented in case reports 6. If cough persists after switching to an ARB, consider other antihypertensive classes.

2. Monitoring after medication change: Follow up within 1-2 weeks after changing therapy to assess for:

   • Resolution of cough
   • Adequate blood pressure control 1

3. Persistence of cough: If cough persists beyond 4 weeks after discontinuation of the ACE inhibitor, consider other etiologies such as:

   • Respiratory infections
   • Asthma
   • GERD
   • Post-nasal drip
   • Heart failure exacerbation 1

4. Avoid misdiagnosis: ACE inhibitor-induced cough is often misattributed to other causes, leading to unnecessary testing and treatment 1, 7. A trial of discontinuation is the most efficient diagnostic approach.

By following this approach, most patients with ACE inhibitor-induced cough will experience resolution of symptoms while maintaining effective blood pressure control.