Is an angiotensin-converting enzyme (ACE) inhibitor-induced cough in a patient with a history of cardiovascular disease and respiratory conditions, such as asthma or chronic obstructive pulmonary disease (COPD), an emergent problem?

ACE Inhibitor Cough is NOT an Emergency

ACE inhibitor-induced cough is a benign, non-emergent adverse effect that does not require urgent intervention or emergency department evaluation. 1 The cough, while bothersome and potentially severe enough to interfere with quality of life, poses no immediate threat to morbidity or mortality and can be managed in the outpatient setting.

Clinical Characteristics

The cough presents as:

• Dry, nonproductive with a tickling or scratching sensation in the throat 1
• Not dose-dependent, so reducing the ACE inhibitor dose will not resolve the problem 1
• Onset ranging from hours after the first dose to weeks or months after initiation 1
• More common in women, nonsmokers, and persons of Chinese origin 1

Why This is Not Emergent

The mechanism involves accumulation of bradykinin and substance P due to ACE inhibition, which sensitizes the cough reflex but does not cause airway obstruction, bronchospasm in most patients, or respiratory compromise 1. This is fundamentally different from angioedema (which IS an emergency) and should not be confused with it 2.

Important Caveat: Rule Out Angioedema

The one true emergency to exclude is angioedema, which can occur with ACE inhibitors and presents with swelling of the face, lips, tongue, or larynx causing airway obstruction 2. If the patient has any swelling or difficulty breathing rather than just cough, this requires immediate emergency evaluation.

Management Algorithm

Step 1: Discontinue the ACE Inhibitor

• The American College of Chest Physicians provides a Grade B recommendation to discontinue ACE inhibitor therapy immediately, as this is the only uniformly effective treatment 1
• Cough typically resolves within 1-4 weeks after cessation, though in some patients it may take up to 3 months 1
• Do not attempt switching to another ACE inhibitor, as this is a class effect and cough will recur 3

Step 2: Switch to an Angiotensin Receptor Blocker (ARB)

• The ACC/AHA guidelines give a Class I, Level A recommendation (highest level) for switching to an ARB such as valsartan or losartan 4
• ARBs have a significantly lower incidence of cough compared to ACE inhibitors 1, 5
• Clinical trials demonstrate that losartan has a cough incidence of 17-29% in patients with prior ACE inhibitor-induced cough, compared to 62-69% with rechallenge of lisinopril 5

Step 3: Timing of the Switch

• Allow at least 36 hours between the last ACE inhibitor dose and starting the ARB 4
• Monitor blood pressure, renal function, and potassium within 1-2 weeks after the switch 4

Special Considerations for Patients with Asthma or COPD

Patients with underlying asthma have an 8-fold increased risk of developing ACE inhibitor-induced cough 6. In these patients:

• The cough is still not emergent unless there is evidence of acute bronchospasm or asthma exacerbation
• Bronchial hyperreactivity and atopy are significant risk factors 6
• While rare cases of bronchospasm have been reported, ACE inhibition is generally safe in patients with obstructive airways disease 3
• If the patient has new wheezing, increased work of breathing, or signs of respiratory distress beyond just cough, this warrants urgent (not emergent) evaluation for asthma exacerbation

Quality of Life Impact

While not emergent, the cough can be severe enough to cause:

• Sleep interference (common and can be severe) 7
• Urinary stress incontinence in women 7
• Significant functional impairment 7

These quality of life impacts justify prompt outpatient management rather than waiting, but do not constitute an emergency 7.

Common Pitfalls to Avoid

• Do not reduce the ACE inhibitor dose - the cough is not dose-dependent and this will not help 1
• Do not try a different ACE inhibitor - this is a class effect and will recur 3
• Do not delay switching to an ARB - there is no benefit to "waiting it out" as the cough will persist as long as the patient takes the ACE inhibitor 1
• Do not confuse cough with angioedema - angioedema with swelling and airway compromise IS an emergency 2