What is the relationship between Lisinopril (Angiotensin-Converting Enzyme Inhibitor) and cough?

From the Guidelines

Lisinopril can cause a persistent dry cough in about 5-35% of patients who take it, and the most effective treatment is to discontinue the medication and switch to an angiotensin receptor blocker (ARB) such as losartan or valsartan, as recommended by the ACCP evidence-based clinical practice guidelines 1. The cough is a common side effect of all ACE inhibitors (like lisinopril, enalapril, ramipril) and typically develops within weeks to months after starting the medication.

• The incidence of ACE inhibitor-induced cough has been reported to be in the range of 5 to 35% among patients treated with these agents 1.
• The onset of ACE inhibitor-induced cough ranges from within hours of the first dose to months after the initiation of therapy 1.
• The cough occurs because ACE inhibitors increase levels of substances called bradykinins and substance P in the lungs, which stimulate cough receptors 1.
• Once lisinopril is discontinued, the cough typically resolves within 1-4 weeks, although it may take up to 3 months to resolve in some patients 1.
• While waiting for the cough to resolve, over-the-counter cough suppressants generally provide little relief for this specific type of cough.
• In patients in whom persistent or intolerable ACE inhibitor-induced cough occurs, therapy should be switched to an ARB, with which the incidence of associated cough appears to be similar to that for the control drug, or to an appropriate agent of another drug class, as recommended by the ACCP guidelines 1.

From the FDA Drug Label

Cough Persistent dry cough (with an incidence of a few percent) has been associated with ACE-inhibitor use and in practice can be a cause of discontinuation of ACE-inhibitor therapy The incidence of cough is shown in Table 1 below Table 1 Study 11 HCTZ Losartan Lisinopril Cough 25% 17% 69% Study 22 Placebo Losartan Lisinopril Cough 35% 29% 62% In a 129-patient trial limited to patients who had had dry cough when they had previously received ACE inhibitors, the incidences of cough in patients who received valsartan, HCTZ, or lisinopril were 20%, 19%, and 69% respectively (p less than 0. 001).

Lisinopril Cough: Lisinopril is associated with a persistent dry cough in a significant percentage of patients, with an incidence of 69% in one study. This is a well-known side effect of ACE inhibitors like lisinopril. The cough is often a cause of discontinuation of ACE-inhibitor therapy. In comparison, other medications like losartan and valsartan have a lower incidence of cough, with rates of 17% and 20% respectively in similar studies 2, 3.

From the Research

Lisinopril Cough Overview

• Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, is known to cause cough in some patients 4, 5, 6, 7, 8.
• The incidence of cough with lisinopril has been compared to other antihypertensive agents, such as losartan, an angiotensin II receptor antagonist, and metolazone, a diuretic 4, 5, 6.
• Studies have shown that the incidence of cough with lisinopril is significantly higher than with losartan and similar to that with hydrochlorothiazide 4 or metolazone 5.

Comparison of Lisinopril with Other Antihypertensive Agents

• A study comparing lisinopril, losartan, and hydrochlorothiazide found that the incidence of cough with losartan (29%) was lower than that with lisinopril (72%) and similar to that with hydrochlorothiazide (34%) 4.
• Another study comparing lisinopril, losartan, and metolazone found that the incidence of cough with losartan (18%) was significantly lower than with lisinopril (97%) and similar to that with metolazone (21%) 5.
• A study comparing lisinopril, losartan, and placebo found that the incidence of dry cough was significantly higher in the lisinopril group (87.5%) than in the losartan and placebo groups (36.7% and 31.4%, respectively) 6.
• A study comparing lisinopril, telmisartan, and placebo found that the incidence of dry cough was significantly higher with lisinopril (60%) than with telmisartan (15.6%) or placebo (9.7%) 7.

Tolerability of Lisinopril

• A prospective and randomized study evaluating the antihypertensive effect and tolerability of losartan, amlodipine, and lisinopril found that patients receiving lisinopril showed a high incidence of coughing (31.7%) 8.
• The study also found that losartan had superior tolerability compared to lisinopril and amlodipine, with fewer episodes of adverse effects and fewer patients experiencing adverse effects 8.