How do Angiotensin Receptor Blockers (ARBs) cause upper respiratory infections?

How Angiotensin Receptor Blockers (ARBs) Cause Upper Respiratory Infections

Unlike ACE inhibitors, ARBs do not directly cause upper respiratory infections but may be associated with them as a side effect reported in clinical trials.

Mechanism of Upper Respiratory Symptoms with ARBs

ARBs work differently from ACE inhibitors, which is important to understand when considering their side effect profiles:

• ACE inhibitors block the enzyme that degrades bradykinin and substance P, causing these substances to accumulate in the upper respiratory tract, leading to the characteristic dry cough (5-35% of patients) 1
• ARBs block angiotensin II receptors without affecting bradykinin metabolism, which is why they don't typically cause the persistent cough seen with ACE inhibitors 1

Reported Incidence in Clinical Trials

According to FDA drug labels:

• Losartan: Upper respiratory infections occurred in 8% of patients vs. 7% in placebo groups 2
• Valsartan: Viral infection (which includes upper respiratory infections) occurred in 3% vs. 2% in placebo 3

Clinical Significance and Management

The relationship between ARBs and upper respiratory infections appears to be:

1. Coincidental rather than causal: The slight increase in URIs with ARBs compared to placebo is small and may represent normal variation rather than a true drug effect
2. Not mediated by the same mechanism as ACE inhibitor cough: ARBs don't significantly affect bradykinin levels 1
3. Much less problematic than with ACE inhibitors: Studies directly comparing ARBs to ACE inhibitors show dramatically lower rates of respiratory symptoms 2, 3

Comparative Data

• In studies of patients who had ACE inhibitor-induced cough, switching to losartan resulted in cough rates similar to placebo (29% vs. 35%) and much lower than with lisinopril (62%) 2
• Similar results were seen with valsartan, where cough rates were 20% compared to 69% with lisinopril 3

Important Clinical Considerations

• If a patient develops persistent upper respiratory symptoms on an ACE inhibitor, switching to an ARB is a reasonable strategy 1
• Upper respiratory infections reported with ARBs are typically mild and rarely require discontinuation of therapy 2, 3
• Other common side effects that may accompany upper respiratory symptoms with ARBs include headache, dizziness, and fatigue 4

Pitfalls to Avoid

• Don't confuse URI symptoms with ACE inhibitor cough: ACE inhibitor cough is typically dry, persistent, and associated with a tickling sensation in the throat 1
• Don't assume all respiratory symptoms are drug-related: Consider other causes of respiratory symptoms, especially during respiratory virus seasons
• Don't unnecessarily discontinue beneficial therapy: The incidence of URIs with ARBs is low and rarely requires discontinuation of therapy that may be providing important cardiovascular or renal benefits 1

In summary, while upper respiratory infections are reported as a side effect of ARBs in clinical trials, they occur at rates only slightly higher than placebo and through mechanisms different from the well-known ACE inhibitor cough. For patients who cannot tolerate ACE inhibitors due to cough, ARBs remain an excellent alternative with a much lower incidence of respiratory side effects.