How long after stopping Angiotensin-Converting Enzyme inhibitors (ACEi) does it take for the dry cough to resolve?

ACE Inhibitor-Induced Cough Resolution Timeline

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

• Cough resolution typically occurs within 1-4 weeks after stopping the ACE inhibitor in most patients 1, 2
• In a subgroup of individuals, cough may linger for up to 3 months after discontinuation 1
• The American College of Chest Physicians recommends assessing for resolution of cough within 1-4 weeks after discontinuation of the ACE inhibitor 2

Risk Factors for ACE Inhibitor-Induced Cough

• Female gender is associated with higher incidence of ACE inhibitor-induced cough 1, 2
• Non-smokers experience this side effect more frequently than smokers 1, 2
• Patients of Chinese or East Asian descent have higher susceptibility 1, 2
• Patients treated for congestive heart failure have a higher incidence (26%) compared to those treated for hypertension (14%) 3
• Patients with underlying asthma or bronchial hyperreactivity may be at higher risk 4

Mechanism of ACE Inhibitor-Induced Cough

• The cough is typically dry and associated with a tickling or scratching sensation in the throat 1, 5
• Possible mechanisms involve accumulation of:
  • Bradykinin and substance P (which are normally degraded by ACE) 1
  • Prostaglandins, production of which may be stimulated by bradykinin 1
• Bradykinin-induced sensitization of airway sensory nerves is a proposed mechanism 1
• Patients with ACE inhibitor-induced cough demonstrate increased cough reflex sensitivity 1

Management Approach

• The only uniformly effective treatment is discontinuation of the ACE inhibitor 1, 2
• Consider switching to an angiotensin receptor blocker (ARB), which has a significantly lower incidence of cough 2, 6
• For patients who absolutely require ACE inhibitor therapy:
  • About 30% of patients may not develop cough after a rechallenge with the same ACE inhibitor 1
  • Pharmacologic agents that may attenuate the cough include:
    • Intermediate dose aspirin (500 mg daily) - shown to reduce cough severity in 93% of patients 7
    • Other agents with some evidence include sodium cromoglycate, theophylline, sulindac, indomethacin, calcium channel blockers, and ferrous sulfate 1

Important Clinical Considerations

• ACE inhibitor-induced cough should be considered regardless of the temporal relationship between medication initiation and cough onset 2
• Avoid unnecessary diagnostic testing before a trial of ACE inhibitor discontinuation 2
• Low-dose aspirin (100 mg) is ineffective for managing ACE inhibitor-induced cough 7
• Replacing one ACE inhibitor with another is generally not recommended as cough will almost always recur 5
• ACE inhibitors may sensitize the cough reflex and potentiate other causes of chronic cough 1