Can Losartan (angiotensin II receptor antagonist) cause a persistent cough?

Losartan and Persistent Cough

Losartan can cause persistent cough, but this occurs much less frequently than with ACE inhibitors and is similar to the background rate seen with placebo or hydrochlorothiazide. 1

Incidence and Mechanism of Cough

• The FDA label for losartan specifically addresses cough, noting that while persistent dry cough is primarily associated with ACE inhibitors, cases of cough including positive re-challenges have been reported with losartan in post-marketing experience 1
• Clinical trials comparing losartan to ACE inhibitors and placebo/hydrochlorothiazide found:
  • In patients with previous ACE inhibitor-induced cough, the incidence of cough with losartan was 17-29%, compared to 62-69% with lisinopril and 25-35% with placebo/hydrochlorothiazide 1
  • This demonstrates that losartan has a significantly lower risk of causing cough than ACE inhibitors 2

Mechanism of Action and Cough

• ACE inhibitor-induced cough occurs due to the accumulation of bradykinin and substance P in the airways 3
• Angiotensin receptor blockers (ARBs) like losartan theoretically should not induce cough because their mechanism of action does not involve inhibition of ACE with resultant elevation of tissue levels of bradykinin and substance P 2
• However, some patients may still experience cough with losartan, though at a much lower rate than with ACE inhibitors 1

Clinical Considerations

When to Suspect Losartan as Cause of Cough

• Consider losartan as a potential cause if:
  • Cough is persistent, dry, and nonproductive
  • Cough developed after starting losartan
  • Other causes of cough (especially pulmonary congestion) have been excluded 2
  • Cough resolves after discontinuation and recurs with rechallenge

Management Options

1. If cough is severe and troublesome with losartan:

   • Consider switching to another antihypertensive medication class (not an ACE inhibitor) 2
   • Monitor blood pressure closely after switching to ensure adequate control 3

2. If there is a compelling reason to continue renin-angiotensin system blockade:

   • Consider trying a different ARB, as there may be individual variations in response 3

Important Caveats

• Most reports of cough with losartan occur in patients with a previous history of ACE inhibitor-induced cough 4
• In some cases, the cough attributed to losartan may be due to a "carry-over effect" from previous ACE inhibitor use, as the ACE inhibitor-induced cough can take up to 4 weeks (sometimes up to 3 months) to resolve completely 3, 4
• Rare case reports exist of losartan-induced cough that resolved after switching to an ACE inhibitor, suggesting individual variability in response 5

Conclusion

While losartan can cause persistent cough in some patients, this side effect is much less common than with ACE inhibitors. For patients who develop troublesome cough with ACE inhibitors, losartan remains a reasonable alternative with a significantly lower risk of cough.