How long after discontinuing Angiotensin-Converting Enzyme (ACE) inhibitors does the cough typically resolve?

Resolution Time of ACE Inhibitor-Induced Cough After Discontinuation

ACE inhibitor-induced cough typically resolves within 1 to 4 weeks after discontinuation of the medication, though in some patients it may persist for up to 3 months. 1

Timeline for Cough Resolution

• Typical resolution timeframe: 1-4 weeks after stopping the ACE inhibitor 1
• Delayed resolution: Up to 3 months in a subgroup of patients 1
• Progressive improvement pattern:
  • Significant subjective improvement often begins within 3-7 days
  • Further reduction in cough continues up to 28 days 2

Mechanism and Characteristics of ACE Inhibitor Cough

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

• Dry and non-productive
• Associated with a tickling or scratching sensation in the throat
• Not dose-dependent 1

The mechanism involves:

• Accumulation of bradykinin and substance P (normally degraded by ACE)
• Prostaglandin production stimulated by bradykinin
• Bradykinin-induced sensitization of airway sensory nerves 1

Risk Factors for ACE Inhibitor Cough

Higher incidence observed in:

• Women 1
• Non-smokers 1
• Persons of Chinese origin 1
• Patients with underlying asthma or bronchial hyperreactivity 3
• Patients treated for heart failure (versus hypertension) 1

Diagnostic Confirmation

The diagnosis of ACE inhibitor-induced cough is confirmed by:

1. Discontinuation of the ACE inhibitor
2. Resolution of cough within the expected timeframe (1-4 weeks, up to 3 months)
3. Absence of other causes of chronic cough 1

Management Options

1. First-line approach: Discontinue the ACE inhibitor - this is the only uniformly effective treatment 1

2. Alternative medications:

   • Angiotensin receptor blockers (ARBs) - significantly lower incidence of cough 1
   • Other antihypertensive classes if appropriate (calcium channel blockers, thiazide diuretics, beta-blockers)

3. If discontinuation is not possible: Several agents have shown ability to attenuate ACE inhibitor cough:

   • Inhaled sodium cromoglycate
   • Theophylline
   • NSAIDs (sulindac, indomethacin)
   • Calcium channel blockers (amlodipine, nifedipine)
   • Ferrous sulfate 1

4. Rechallenge option:

   • In patients with compelling reasons to use ACE inhibitors, a repeat trial may be attempted after cough resolution
   • Approximately 30% of patients may not develop cough with rechallenge 1

Physiological Changes During Resolution

As cough resolves after ACE inhibitor discontinuation:

• Sensitivity to inhaled capsaicin decreases over 28 days
• Wheal area produced by intradermal bradykinin significantly reduces (majority of effect by day 3)
• Wheal area to intradermal substance-P also declines (significant changes by day 14) 2

Important Clinical Considerations

• ACE inhibitor cough is often misdiagnosed, leading to unnecessary testing
• The onset of cough can occur within hours of the first dose or be delayed for weeks to months
• ACE inhibitors may sensitize the cough reflex, potentially exacerbating other causes of cough 1
• Monitoring for resolution confirms the diagnosis and guides further management

Remember that complete resolution of cough is the expected outcome after discontinuation of the ACE inhibitor, though patience may be required in cases where resolution takes longer than the typical 1-4 week period.