Lisinopril induced cough
Pro Research Analysisby 
Searched over 200M research papers
Lisinopril-Induced Cough: Incidence and Risk Factors
Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, is well known to cause a persistent, dry cough in a significant number of patients. The reported incidence of lisinopril-induced cough varies, with studies showing rates from about 8.5% up to 18.1% among users, which is higher than with many other antihypertensive medications such as nifedipine or hydrochlorothiazide 1357. In comparison, the risk of cough with ACE inhibitors as a class is more than double that of placebo and significantly higher than with angiotensin receptor blockers (ARBs) or calcium channel blockers (CCBs) .
Gender and Other Risk Factors for Lisinopril-Induced Cough
Research consistently shows a higher incidence of lisinopril-induced cough in women compared to men. In large clinical studies, women reported cough three times more often than men (12.6% vs. 4.4%) when treated with lisinopril, a difference not observed with other antihypertensive drugs or during placebo periods 137. Nonsmokers also appear to be at higher risk than smokers . The reason for these gender and smoking-related differences remains unclear .
Onset, Duration, and Characteristics of Lisinopril-Induced Cough
The cough associated with lisinopril is typically described as dry, nonproductive, and persistent, often accompanied by a tickling or irritating sensation in the throat 457. It usually develops within the first week to four weeks of starting therapy, but can occur at any time during treatment. The cough generally resolves within one to four weeks after discontinuing lisinopril 457. No clear relationship has been found between the dose of lisinopril and the likelihood of developing a cough .
Mechanisms Behind Lisinopril-Induced Cough
The most widely accepted explanation for lisinopril-induced cough is the accumulation of bradykinin and substance P, which are normally broken down by ACE. Lisinopril inhibits this breakdown, leading to increased levels of these mediators, which can stimulate cough reflex pathways in the lungs and central nervous system 245. Experimental studies in animals have shown that lisinopril can directly increase cough reflex sensitivity through central mechanisms involving bradykinin and substance P .
Comparison with Other Antihypertensive Agents
Lisinopril and other ACE inhibitors are more likely to cause cough than ARBs such as losartan or valsartan, which do not inhibit bradykinin breakdown. Studies in patients with a history of ACE inhibitor-induced cough found that switching to an ARB resulted in a much lower incidence of cough, similar to placebo 689. Among ACE inhibitors, lisinopril has a moderate risk of inducing cough compared to others in its class, but all ACE inhibitors share this side effect to some extent 579.
Management and Alternatives
For patients who develop a bothersome cough on lisinopril, discontinuation of the drug usually leads to resolution of symptoms within a few weeks 457. Switching to an ARB is an effective alternative, as these agents provide similar blood pressure control without the risk of cough 689. In some cases, nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to reduce cough severity, but this is not a standard approach 47.
Conclusion
Lisinopril-induced cough is a common and sometimes troublesome side effect, especially in women and nonsmokers. The cough is typically dry, persistent, and resolves after stopping the medication. The underlying mechanism involves increased bradykinin and substance P levels. For patients who cannot tolerate the cough, switching to an ARB is a well-supported alternative.
Sources and full results
Most relevant research papers on this topic