From the Guidelines
To manage a dry cough associated with ACE inhibitors, the most effective approach is to switch to an angiotensin receptor blocker (ARB) such as losartan, valsartan, or irbesartan, as they provide similar cardiovascular benefits without causing cough, as recommended by the ACCP evidence-based clinical practice guidelines 1. The cough occurs because ACE inhibitors increase bradykinin levels in the lungs, which stimulates nerve endings and triggers the cough reflex, affecting approximately 5-35% of patients taking ACE inhibitors and significantly impacting quality of life 1. Some key points to consider when managing ACE inhibitor-induced cough include:
- Discontinuing ACE inhibitor therapy is the only uniformly effective treatment for ACE inhibitor-induced cough, with cough resolution expected within 1-4 weeks 1.
- If cessation of ACE inhibitor therapy is not an option, pharmacologic therapy aimed at suppressing cough may be attempted, including sodium cromoglycate, theophylline, sulindac, indomethacin, amlodipine, nifedipine, ferrous sulfate, and picotamide, although the quality of evidence for these options is fair and the net benefit is intermediate 1.
- Reducing the ACE inhibitor dose may decrease cough severity while maintaining some therapeutic benefit, but this approach may not be suitable for all patients.
- Temporary symptom relief can be achieved with over-the-counter options like dextromethorphan (Robitussin DM) 10-20 mg every 4 hours, throat lozenges, or a teaspoon of honey. It is essential to note that ARBs do not cause cough and may be a suitable alternative for patients who experience persistent or intolerable ACE inhibitor-induced cough, with a similar incidence of associated cough to control drugs 1.
From the Research
Management of Dry Cough Associated with ACEIs
To manage a dry cough associated with Angiotensin-Converting Enzyme Inhibitors (ACEIs), several strategies can be employed:
- Temporarily discontinuing the ACEI upon reporting the incidence of cough and reintroducing it after the cough has remitted, as suggested by 2.
- Adding calcium channel blockers to ACEIs, which can help mitigate the cough, as proposed by 2.
- Switching to alternative drugs such as angiotensin receptor blockers if intolerable symptoms recur, after excluding all other possible causes of cough, as recommended by 2 and 3.
Incidence and Mechanisms of Cough
The incidence of dry cough in patients receiving ACEIs varies among individual ACEIs, with perindopril having the lowest incidence, as noted by 2 and 3. The mechanisms of cough associated with ACEIs are thought to involve multiple factors, with the bradykinin theory being the most commonly appealed hypothesis, as discussed by 2 and 3.
Clinical Implications
In clinical practice, the incidence of ACEI-induced cough should not be considered a class effect, and patients may benefit from switching from one ACEI to another, as suggested by 3. Every effort should be made to enable patients to continue ACEI therapy to reduce adverse cardiovascular outcomes and improve survival, as emphasized by 3. Additionally, a challenge/re-challenge approach can be used to determine if re-introduction of ACEI is associated with recurrence of symptoms, as proposed by 3.
Misdiagnosis and Mistreatment
There is a significant risk of misdiagnosis and mistreatment of ACEI-induced cough, with some physicians attempting to treat it with antitussive agents instead of recommended ACEI substitution, as reported by 4. This highlights the importance of recognizing ACEI-induced cough and managing it appropriately to avoid unnecessary treatment and potential harm to patients.
Pathophysiological Mechanisms
The pathophysiological mechanisms underlying ACEI-induced cough are complex and involve increased inflammatory states in the airways of susceptible individuals, as discussed by 5. This may lead to a cough with pathophysiological features similar to those seen in asthma, emphasizing the need for careful consideration and management of ACEI-induced cough in clinical practice.