Management of Lisinopril-Induced Dry Cough
Discontinue lisinopril immediately and switch to an angiotensin receptor blocker (ARB) such as losartan or valsartan. 1, 2
Why Discontinuation is Essential
- ACE inhibitor-induced cough is a class effect occurring in 5-35% of patients, meaning switching to another ACE inhibitor (enalapril, ramipril, captopril) will simply reproduce the same cough. 1, 3
- The cough is not dose-dependent, so reducing the lisinopril dose will not resolve the problem and only delays appropriate management. 2, 4
- Discontinuation is the only uniformly effective intervention, with the American College of Chest Physicians providing a Grade B recommendation for immediate cessation. 1, 2
Expected Timeline for Resolution
- Cough typically resolves within 1-4 weeks after stopping lisinopril, with a median resolution time of approximately 26 days (3.5 weeks). 1, 2
- A minority of patients may require up to 3 months for complete resolution. 1, 2
- If cough persists beyond 4 weeks, evaluate for alternative causes including gastroesophageal reflux disease, heart failure-related pulmonary congestion, or asthma. 2
Optimal Replacement Strategy
- Switch to an ARB (losartan, valsartan, or other ARBs), which have a cough incidence comparable to placebo and significantly lower than ACE inhibitors. 2, 5
- The FDA label for losartan documents that in patients with prior ACE inhibitor-induced cough, losartan produced cough in only 17-29% versus 62-69% with lisinopril rechallenge. 5
- Allow at least 36 hours between the last lisinopril dose and starting an ARB to minimize risk of adverse effects. 2
- Monitor blood pressure, renal function, and potassium levels within 1-2 weeks after switching. 2
Important Clinical Pitfalls to Avoid
- Do not attempt a different ACE inhibitor – all agents (captopril, enalapril, lisinopril, ramipril, quinapril) cause cough at similar rates due to the shared mechanism of bradykinin and substance P accumulation. 1, 3
- Do not assume timing excludes ACE inhibitors – while cough often develops within the first week, onset can be delayed for weeks, months, or even up to one year after initiation. 2, 4, 3
- Do not pursue extensive diagnostic workup before a trial of discontinuation, as this increases unnecessary costs and patient burden. 2
- Be aware that ACE inhibitors can sensitize the cough reflex, potentially amplifying cough from other underlying conditions. 2
Risk Factors for ACE Inhibitor-Induced Cough
- Female gender – women experience cough rates of 37.9% versus 15.5% in men. 2, 4
- Non-smokers are more susceptible than smokers. 2, 4
- Chinese or East Asian ethnicity has higher incidence rates. 2
- Heart failure patients experience cough more frequently (26%) than hypertensive patients (14%). 2, 6
Alternative Management (Rarely Appropriate)
- If ACE inhibitor continuation is absolutely unavoidable for compelling clinical reasons, indomethacin 50 mg twice daily has shown some efficacy in reducing cough severity, though discontinuation remains the definitive treatment. 2, 4
- One study found that approximately 30% of patients with confirmed ACE inhibitor-induced cough did not develop cough after a third rechallenge, so a repeat trial may be considered only if there is a compelling reason to use an ACE inhibitor over an ARB. 1
- However, in practical clinical medicine, switching to an ARB is far more appropriate than attempting rechallenge or adjunctive therapy. 1, 2
Special Consideration for Heart Failure
- For patients with heart failure, the European Journal of Heart Failure guidelines note that ACE inhibitor-induced cough "rarely requires treatment discontinuation" in the heart failure population, but when cough is very troublesome (e.g., stopping the patient from sleeping), substitution with an ARB is appropriate. 1
- The cough must be proven due to ACE inhibition through withdrawal and rechallenge before switching. 1
- Always exclude pulmonary edema as a cause of new or worsening cough in heart failure patients. 1