Understanding the Differences: Do ARBs Cause Cough and Angioedema?

October 12, 2025 •

3 min read

While a dry, persistent cough affects up to 10% of patients on ACE inhibitors, the risk of developing a cough with angiotensin receptor blockers (ARBs) is significantly lower and comparable to a placebo. This key difference in side effects directly addresses the question: do ARBs cause cough and angioedema? This article will explore the pharmacological reasons behind these differing risk profiles.

Quick Summary

This article examines why angiotensin receptor blockers (ARBs) have a much lower incidence of cough and angioedema compared to ACE inhibitors. It delves into the distinct mechanisms of action that affect bradykinin levels and details the small but real risk of angioedema with ARBs, especially for those with a history of ACE inhibitor-related reactions.

Key Points

Low Cough Incidence: ARBs rarely cause the persistent, dry cough commonly associated with ACE inhibitors because they do not increase bradykinin levels.
Reduced Angioedema Risk: The risk of angioedema with ARBs is very low compared to ACE inhibitors, but it is not zero.
Bradykinin Mechanism: The key difference lies in the mechanism of action. ACEIs inhibit the enzyme that breaks down bradykinin, causing it to accumulate, while ARBs block receptors and do not interfere with bradykinin breakdown.
Cross-Reactivity: Patients with a history of ACE inhibitor-induced angioedema have a small, elevated risk of experiencing angioedema with an ARB.
Safe Alternative: For most patients intolerant to ACE inhibitors, switching to an ARB is a safe and effective therapeutic alternative.
Emergency Awareness: All patients on ARBs should be aware of the rare angioedema risk and seek immediate medical help if they experience any swelling of the face, lips, or throat.

ARBs vs. ACE Inhibitors: A Pharmacological Distinction

To understand why angiotensin receptor blockers (ARBs) are much less likely to cause a persistent cough or angioedema than angiotensin-converting enzyme inhibitors (ACEIs), it is essential to look at their different mechanisms of action within the renin-angiotensin-aldosterone system (RAAS).

The ACE Inhibitor Mechanism

ACEIs, which typically end in "-pril," work by blocking the angiotensin-converting enzyme (ACE). This enzyme is responsible for converting angiotensin I into angiotensin II and also breaking down bradykinin, a vasodilator. By inhibiting ACE, these medications increase bradykinin levels, which is the primary cause of associated side effects like cough and, rarely, angioedema. The accumulation of bradykinin in the lungs can cause cough, while elevated levels can also increase vascular permeability, leading to angioedema.

The ARB Mechanism

ARBs, often ending in "-sartan," block the angiotensin II type 1 (AT1) receptors, preventing angiotensin II from exerting its effects. Unlike ACEIs, ARBs do not inhibit the breakdown of bradykinin, resulting in a significantly lower risk of cough. Clinical studies indicate the frequency of cough with ARBs is similar to placebo.

ARBs and Angioedema: A Small but Real Risk

While angioedema is considerably less common with ARBs than with ACEIs, a small risk still exists. Patients with a history of ACEI-induced angioedema have a slightly increased risk of a similar reaction when switching to an ARB. Some theories suggest this might involve a feedback increase in angiotensin II, potentially leading to minor ACE inhibition or activation of AT2 receptors, contributing to bradykinin generation in susceptible individuals.

Comparing ACE Inhibitors and ARBs


Feature	ACE Inhibitors (e.g., Lisinopril, Ramipril)	Angiotensin Receptor Blockers (ARBs) (e.g., Losartan, Valsartan)
Mechanism of Action	Inhibits the ACE enzyme, preventing conversion of angiotensin I to angiotensin II and blocking bradykinin breakdown.	Blocks the AT1 receptor, preventing angiotensin II from binding.
Cough Incidence	High (5-35%). A common reason for discontinuation.	Low (comparable to placebo). Does not affect bradykinin breakdown.
Angioedema Risk	Low but higher incidence (~0.1-2%) than with ARBs.	Very low, but non-zero. Higher risk in patients with prior ACEI-induced angioedema.
Associated Substance	High levels of bradykinin.	Low levels of bradykinin, though some increase is possible via alternative pathways in susceptible individuals.
Switching Therapy	If a cough or angioedema occurs, switching to an ARB is a common clinical practice.	Generally well-tolerated by patients with ACEI-induced side effects, though caution is needed for prior angioedema.

Management and Clinical Considerations

For patients experiencing an ACEI-induced cough, switching to an ARB is a standard and effective approach, with most patients not developing a cough on the new medication. While switching to an ARB is also considered after ACEI-induced angioedema, it requires careful consideration and monitoring due to the small cross-reactivity risk. Patients should be educated on angioedema symptoms and seek immediate medical attention if they occur while on an ARB. The risk of angioedema in patients without a history of ACEI reaction is very low, but awareness remains crucial.

Conclusion

ARBs present a significantly lower risk of cough and angioedema compared to ACE inhibitors due to their distinct mechanism of action which does not lead to bradykinin accumulation. While the risk of angioedema with ARBs is rare, particularly for those with a prior ACEI reaction, it is not absent. For patients intolerant to ACE inhibitors, ARBs offer a safe and effective treatment alternative for cardiovascular conditions when appropriate precautions are taken and patients are informed about potential symptoms.

For more information on managing ACE inhibitor side effects and ARB use, consult the Cleveland Clinic Journal of Medicine.

Frequently Asked Questions

The main difference is their effect on bradykinin. ACE inhibitors block the enzyme that breaks down bradykinin, causing it to accumulate and leading to side effects like cough and angioedema. ARBs do not block this enzyme, so they do not cause bradykinin buildup and have a lower risk of these side effects.

No, it is highly unlikely. Since the mechanism for ARB side effects does not involve the same bradykinin pathway, patients who developed a cough on an ACE inhibitor can typically tolerate an ARB without the cough returning.

The risk of angioedema with an ARB is very low compared to ACE inhibitors, but it is not nonexistent. The risk is slightly higher for patients with a history of ACE inhibitor-induced angioedema, though still considered low.

While the risk is low, caution is advised. Studies show a small percentage of patients with a history of ACEI-induced angioedema will develop angioedema on an ARB. Your doctor should weigh the benefits and risks and monitor you closely.

Seek immediate medical attention if you notice any swelling of your face, lips, tongue, or throat, or have difficulty breathing. The medication should be discontinued immediately under a doctor's supervision.

Yes, although it is rare, ARB-induced angioedema can, in some cases, affect internal organs, a condition known as visceral angioedema, which can cause abdominal pain.

Historically, ACE inhibitors were the first to be approved and were often cheaper. While ARBs are typically better tolerated, both classes are effective. Decisions often depend on clinical guidelines, patient history, and cost.