Can lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor) cause a dry cough?

Lisinopril and Dry Cough: Diagnosis and Management

Lisinopril definitively causes dry cough in 5-35% of patients, and this is a well-established class effect of all ACE inhibitors that requires discontinuation of the medication for resolution. 1

Mechanism and Clinical Presentation

ACE inhibitor-induced cough has several key characteristics:

• Typically dry, non-productive cough
• Associated with a tickling or scratching sensation in the throat
• Not dose-dependent
• Occurs more commonly in:
  • Women
  • Nonsmokers
  • Persons of Chinese origin 1

The mechanism involves:

• Accumulation of bradykinin and substance P in the upper airway due to reduced degradation by ACE
• Stimulation of prostaglandin production
• Sensitization of airway sensory nerves 1

Timing and Diagnosis

The cough may:

• Begin within hours of the first dose
• Develop weeks to months after starting therapy
• Persist as long as the medication is continued
• Resolve within 1-4 weeks after discontinuation (though may take up to 3 months in some patients) 1

When evaluating a patient with cough on lisinopril:

• Consider ACE inhibitors as causative regardless of the temporal relationship between medication initiation and cough onset
• The diagnosis is confirmed by resolution of cough after discontinuation 1

Management Algorithm

1. Discontinue lisinopril

   • This is the only uniformly effective treatment for ACE inhibitor-induced cough 1
   • Complete resolution typically occurs within 1-4 weeks but may take up to 3 months 1

2. Switch to an angiotensin receptor blocker (ARB)

   • ARBs like valsartan or losartan have significantly lower incidence of cough compared to ACE inhibitors 2, 3
   • In clinical trials comparing ARBs to ACE inhibitors:
     • Valsartan: 2.6% cough incidence vs. 7.9% with ACE inhibitors 2
     • Losartan: 17-29% cough incidence vs. 62-69% with lisinopril (in patients with previous ACE inhibitor cough) 3

3. Consider other antihypertensives if ARBs are not tolerated

   • Calcium channel blockers
   • Thiazide diuretics
   • Beta-blockers

Special Considerations

• In rare cases, cough may spontaneously resolve despite continued ACE inhibitor therapy 4
• Some patients may tolerate one ACE inhibitor but not another, though this is uncommon 5
• Very rarely, ARBs may also cause cough in sensitive individuals 6

Pitfalls to Avoid

1. Misattribution of cause: Don't assume all cough in patients on lisinopril is due to the medication. Consider other common causes like respiratory infections, asthma, GERD, or post-nasal drip 1

2. Delayed recognition: ACE inhibitor cough may develop months after starting therapy, making the association less obvious 1

3. Inadequate follow-up: Some patients may experience prolonged cough for up to 3 months after discontinuation 1

4. Unnecessary testing: If the clinical picture is consistent with ACE inhibitor-induced cough, a trial of discontinuation is more appropriate than extensive diagnostic testing 1

By following this approach, you can effectively diagnose and manage lisinopril-induced cough while maintaining appropriate treatment for the patient's underlying condition.