Can Losartan (angiotensin II receptor antagonist) cause a chronic cough in a patient with hypertension?

Losartan and Chronic Cough

Losartan does NOT cause chronic cough at rates higher than placebo and is specifically the recommended alternative for patients who develop ACE inhibitor-induced cough. 1, 2

Evidence from Clinical Trials

The FDA label for losartan includes two prospective, randomized, controlled trials specifically designed to assess cough incidence in hypertensive patients with prior ACE inhibitor-induced cough 3:

• Study 1: Cough occurred in 17% of losartan patients vs. 69% with lisinopril and 25% with hydrochlorothiazide 3
• Study 2: Cough occurred in 29% of losartan patients vs. 62% with lisinopril and 35% with placebo 3

These data demonstrate that losartan's cough incidence is similar to placebo or hydrochlorothiazide, and dramatically lower than ACE inhibitors. 3

Mechanism Explaining the Difference

• ACE inhibitors cause cough in 5-35% of patients through accumulation of bradykinin and substance P, which occurs because these drugs inhibit ACE (which is also kininase II) 1
• ARBs like losartan do NOT inhibit ACE and therefore do not cause bradykinin accumulation, explaining their placebo-level cough rates 1, 2
• The American College of Chest Physicians confirms ARBs have cough rates of approximately 2-3%, similar to placebo, compared to 7.9% for ACE inhibitors 1

Critical Clinical Caveat: Carry-Over Effect

If a patient develops cough shortly after switching from an ACE inhibitor to losartan, this is almost certainly carry-over cough from the prior ACE inhibitor, not losartan-induced cough. 4

• In one observational study, cough was the most frequent event in the first month with losartan, but 91% of patients who discontinued losartan due to cough had previously been prescribed an ACE inhibitor, and 86% had previously experienced ACE inhibitor cough 4
• When reports of cough in days 1-7 were excluded (to eliminate carry-over), cough rates were significantly higher for ACE inhibitors compared to losartan (rate ratios 1.5-5.7, all P<0.03) 4
• ACE inhibitor-induced cough typically resolves within 1-4 weeks after discontinuation, though may take up to 3 months in some patients 1, 2

Rare Exception: Idiosyncratic Losartan-Induced Cough

• One case report describes a 23-year-old woman who developed cough 3 days after starting losartan (ACE inhibitor-naive), which resolved after switching to enalapril 5
• This represents an extremely rare idiosyncratic reaction and should not change clinical practice, as the overwhelming evidence demonstrates losartan does not cause cough through any class mechanism 5

Clinical Recommendation Algorithm

For a patient on losartan who develops chronic cough:

1. Do NOT attribute the cough to losartan - investigate other causes first (pulmonary edema, asthma, GERD, postnasal drip, lung disease) 2
2. If the patient was recently switched from an ACE inhibitor (within 3 months), assume carry-over cough - continue losartan and reassure the patient the cough will resolve 1, 4
3. If the patient has been on losartan long-term without recent ACE inhibitor exposure, losartan is almost certainly not the cause 3, 4
4. Only in the extraordinarily rare case where all other causes are excluded and temporal relationship is clear should losartan be considered as a potential cause 5

Postmarketing Surveillance Note

• The FDA label notes that "cases of cough, including positive re-challenges, have been reported with the use of losartan in postmarketing experience," but emphasizes this is rare and occurs at rates similar to placebo in controlled trials 3