Does lisinopril (angiotensin-converting enzyme (ACE) inhibitor) cause a dry cough?

Does Lisinopril Cause Dry Cough?

Yes, lisinopril definitively causes dry cough as a well-documented class effect of ACE inhibitors, occurring in 5-35% of patients, and this is confirmed by both FDA labeling and major clinical guidelines. 1, 2

Clinical Characteristics of ACE Inhibitor-Induced Cough

The cough presents with specific features that distinguish it from other causes:

• Dry, nonproductive cough with a tickling or scratching sensation in the throat 1, 3
• Onset timing is highly variable, ranging from hours after the first dose to weeks or months after starting therapy 1, 4
• Not dose-dependent, meaning increasing or decreasing the dose will not resolve the cough 4, 5
• FDA labeling confirms cough occurred 2.5% more frequently than placebo in hypertension trials 2

Risk Factors for Higher Incidence

Certain patient populations experience this adverse effect more frequently:

• Female gender has higher incidence compared to males 1, 4
• Non-smokers are more susceptible than smokers 1, 4
• Chinese ethnicity or East Asian descent shows significantly higher rates 1, 4
• Heart failure patients experience cough more frequently than those treated for hypertension alone 1, 4

Evidence Strength

The evidence supporting lisinopril-induced cough is robust across multiple study types:

• Network meta-analysis of 135 RCTs with 45,420 patients demonstrated ACE inhibitors have 2.21 times the risk of cough versus placebo, with lisinopril ranking in the middle range (SUCRA 64.7%) among ACE inhibitors 6
• Head-to-head trials show 87.5% cough incidence with lisinopril versus 31.4% with placebo in patients with prior ACE inhibitor-induced cough 7
• Another comparative trial demonstrated 60% cough incidence with lisinopril versus 9.7% with placebo 8

Management Algorithm

The American College of Chest Physicians provides Grade B recommendation for immediate discontinuation of lisinopril, as this is the only uniformly effective treatment 4, 3:

1. Discontinue lisinopril immediately upon diagnosis of ACE inhibitor-induced cough 4, 3
2. Expect resolution within 1-4 weeks after cessation 1, 4, 3
3. Switch to an angiotensin receptor blocker (ARB) such as valsartan or losartan, which carries Class I, Level A recommendation from ACC/AHA guidelines 1, 3
4. Allow at least 36 hours between last lisinopril dose and starting ARB to minimize adverse effects 1, 3
5. Monitor blood pressure, renal function, and potassium within 1-2 weeks after the switch 1, 3

Critical Pitfalls to Avoid

• Do not try switching to another ACE inhibitor, as cough will almost always recur since this is a class effect occurring with all ACE inhibitors 1, 5
• Do not perform extensive diagnostic workup before trial of discontinuation, as this increases unnecessary costs and patient burden 1
• Do not discontinue beta-blocker therapy when switching from ACE inhibitor to ARB in heart failure patients, as both are essential guideline-directed medical therapy 4

ARB Alternative Evidence

ARBs demonstrate significantly lower cough incidence compared to lisinopril:

• Losartan showed 36.7% cough incidence versus 87.5% with lisinopril in patients with prior ACE inhibitor-induced cough 7
• Telmisartan demonstrated 15.6% cough incidence versus 60% with lisinopril 8
• Overall, ACE inhibitors have 3.2 times the risk of cough compared to ARBs 6