Can Losartan (angiotensin II receptor antagonist) cause cough or breathing issues?

From the Guidelines

Losartan is unlikely to cause cough or breathing issues as a side effect, making it a suitable alternative for patients who experience these symptoms with ACE inhibitors. The mechanism of action of losartan, an angiotensin II receptor antagonist, does not involve the inhibition of ACE, which is responsible for the elevation of tissue levels of bradykinin and substance P, leading to cough 1. According to the ACCP evidence-based clinical practice guidelines 1, losartan has been associated with a low incidence of cough, similar to that of the diuretic hydrochlorothiazide, in patients with a history of ACE inhibitor-induced cough.

Some key points to consider when prescribing losartan include:

• The incidence of cough associated with losartan is lower compared to ACE inhibitors 1
• Losartan can be used as an alternative therapy in patients who experience persistent or intolerable ACE inhibitor-induced cough 1
• Patients who develop angioedema, a rare but serious allergic reaction, may experience breathing-related issues such as shortness of breath or wheezing, and should seek immediate medical attention if they experience any difficulty breathing while taking losartan
• The standard dosing for losartan ranges from 25-100 mg once daily, with 50 mg being a common starting dose for hypertension [no specific reference to dosing in (1), but this is general medical knowledge].

It is essential to monitor patients for any adverse reactions, including breathing issues, and adjust treatment accordingly. However, based on the current evidence 1, losartan is a viable option for patients who require alternative therapy due to ACE inhibitor-induced cough.

From the FDA Drug Label

Respiratory, Thoracic and Mediastinal Disorders: Dyspnea. Cases of cough, including positive re-challenges, have been reported with the use of losartan in postmarketing experience. The incidence of cough associated with losartan therapy, in a population that all had cough associated with ACE-inhibitor therapy, is similar to that associated with hydrochlorothiazide or placebo therapy

Losartan may cause breathing issues, as evidenced by reports of dyspnea. Additionally, cough has been reported in patients taking losartan, particularly in those who had previously experienced cough with ACE-inhibitor therapy. However, the incidence of cough with losartan is similar to that of placebo or hydrochlorothiazide therapy 2.

• Key points:
  • Dyspnea reported as a respiratory disorder
  • Cough reported in postmarketing experience
  • Incidence of cough similar to placebo or hydrochlorothiazide therapy
• Main idea: Losartan may cause breathing issues and cough, but the incidence of cough is similar to that of placebo.

From the Research

Losartan and Breathing Issues

• Losartan, an angiotensin II receptor antagonist, is generally not associated with cough or breathing issues, unlike angiotensin-converting enzyme (ACE) inhibitors 3, 4, 5, 6, 7.
• However, there have been reports of cough in patients taking losartan, although the incidence is significantly lower compared to ACE inhibitors 4, 5, 6.
• A study found that the incidence of dry cough was significantly higher in patients treated with lisinopril (an ACE inhibitor) compared to losartan or placebo 4.
• Another study reported a case of losartan-induced cough that resolved after substitution with enalapril (an ACE inhibitor) 3.
• The overall incidence of clinical and laboratory adverse events, including cough, was similar between losartan and placebo groups in a study of approximately 3800 patients with mild-to-severe essential hypertension 5.

Comparison with ACE Inhibitors

• ACE inhibitors are known to cause cough in a significant number of patients, which is believed to be related to the accumulation of bradykinin, substance P, and prostaglandins resulting from the inhibition of ACE 3, 4.
• Losartan, as an angiotensin II receptor antagonist, does not inhibit ACE and therefore is not expected to cause cough 3, 4, 5, 6, 7.
• However, a study found that rates of cough were significantly higher for ACE inhibitors compared to losartan, even after excluding reports of cough between days 1-7 to reduce the impact of carry-over effects 6.

Clinical Safety and Tolerability

• Losartan has been shown to be well tolerated and safe in clinical trials, with a similar incidence of adverse events compared to placebo 5, 7.
• The most frequently reported adverse events with losartan were headache, upper respiratory tract infection, dizziness, and asthenia/fatigue, but only dizziness occurred more frequently (> or = 1%) in the losartan-treated groups 5.
• Cough occurred in 3.1% of patients treated with losartan and 2.6% of patients treated with placebo in a study of approximately 3800 patients with mild-to-severe essential hypertension 5.