From the Guidelines
Angiotensin-Converting Enzyme (ACE) inhibitors are known to cause a persistent dry cough in approximately 5-35% of patients taking these medications. This side effect is a well-documented class effect of ACE inhibitors, and it is not dose-dependent 1. The cough typically develops within weeks to months after starting therapy and is more common in women, non-smokers, and those of Asian descent.
Causes and Mechanism
The cough is thought to occur because ACE inhibitors prevent the breakdown of bradykinin and substance P in the lungs, leading to increased sensitivity of cough receptors 1. Specific ACE inhibitors that can cause cough include lisinopril, enalapril, ramipril, captopril, benazepril, fosinopril, quinapril, perindopril, and trandolapril.
Management and Treatment
If a patient develops a troublesome cough while on an ACE inhibitor, the medication should not be abruptly discontinued but rather discussed with their healthcare provider. An alternative medication such as an Angiotensin II Receptor Blocker (ARB) may be substituted, as ARBs work through a different mechanism and rarely cause cough 1. The ACE inhibitor-induced cough typically resolves within 1-4 weeks after discontinuation of the medication.
Key Points
- ACE inhibitors can cause a persistent dry cough in approximately 5-35% of patients.
- The cough is not dose-dependent and can occur at any time after starting therapy.
- ARBs are a suitable alternative for patients who develop a troublesome cough while on ACE inhibitors.
- The ACE inhibitor-induced cough typically resolves within 1-4 weeks after discontinuation of the medication.
From the FDA Drug Label
Cough Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough
- ACE inhibitors, such as enalapril, cause cough due to the inhibition of the degradation of endogenous bradykinin.
- This cough is persistent and nonproductive, but it always resolves after discontinuation of therapy 2.
From the Research
Medications that Cause Cough
- Angiotensin-Converting Enzyme (ACE) inhibitors are known to cause cough as a common adverse effect, with an incidence of around 10% in patients treated with these medications 3.
- The mechanisms underlying ACE inhibitor-induced cough are linked to suppression of kininase II activity, leading to an accumulation of kinins, substance P, and prostaglandins 3.
- Studies have shown that cough is a class effect of ACE inhibitors, with no clear difference between individual substances, and replacement with another ACE inhibitor is not recommended as the cough will almost always recur 3.
Specific ACE Inhibitors and Cough
- Enalapril and captopril have been associated with a higher incidence of cough compared to placebo 4.
- Lisinopril has also been reported to cause cough, although the incidence may vary depending on the study population and dosage 5.
- Other ACE inhibitors, such as ramipril and trandolapril, may also cause cough, although the incidence may be lower compared to enalapril and captopril 4, 6.