Management of ACE Inhibitor-Induced Cough

Diagnosis and Prevalence

ACE inhibitor-induced cough occurs in approximately 5-35% of patients treated with these medications 4
The cough is typically dry and associated with a tickling or scratching sensation in the throat 4
Cough may develop within hours of the first dose or be delayed for weeks to months after starting therapy 4
ACE inhibitor-induced cough occurs more frequently in women, nonsmokers, and persons of Chinese origin 4, 5

The mechanism involves accumulation of bradykinin and substance P in the upper airway, along with prostaglandins stimulated by bradykinin 1, 6
Bradykinin-induced sensitization of airway sensory nerves has been proposed as a potential mechanism 1
Subjects with ACE inhibitor-induced cough demonstrate increased cough reflex sensitivity to experimental stimulation with capsaicin 1

Discontinue the ACE inhibitor - this is the only uniformly effective intervention 1
Diagnosis is confirmed by resolution of cough, usually within 1-4 weeks of cessation, though it may take up to 3 months in some patients 1
Switch to an angiotensin receptor blocker (ARB) as first-line alternative - ARBs do not affect bradykinin metabolism and typically do not cause cough 3, 5
If ARBs are contraindicated or not tolerated, consider a calcium channel blocker (CCB) 3, 5
Thiazide-like diuretics can also be considered if CCBs are not suitable 3
Several agents have demonstrated the ability to attenuate ACE inhibitor-induced cough in randomized, double-blind, placebo-controlled trials:
- Inhaled sodium cromoglycate 1, 5
- Theophylline 1, 5
- Calcium channel antagonists (amlodipine, nifedipine) 1, 3
- NSAIDs (sulindac, indomethacin) - use with caution in elderly patients 1, 5
- Ferrous sulfate 1, 5

In approximately 30% of patients with ACE inhibitor-induced cough who have been challenged and dechallenged twice, cough may not recur after a third trial of ACE inhibitor therapy 1
For patients with compelling indications for ACE inhibitor therapy, a repeat trial may be attempted if the cough resolves after initial discontinuation 1
Always exclude other common causes of cough (respiratory infections, heart failure, pulmonary disease, post-nasal drip) before attributing it to ACE inhibitors 5

After switching from an ACE inhibitor to an alternative medication, monitor blood pressure closely to ensure adequate control 3
If blood pressure is not adequately controlled on monotherapy, combination therapy may be necessary 3