Valsartan for ACE Inhibitor-Induced Cough
Valsartan is highly effective for treating ACE inhibitor-induced cough, with significantly lower cough incidence (19.5%) compared to ACE inhibitors (68.9%) while maintaining similar antihypertensive efficacy. 1
Mechanism and Evidence
- ACE inhibitor-induced cough is a well-documented class effect occurring in 5-35% of patients taking these medications, characterized by a dry cough with a tickling sensation in the throat 2, 3
- Valsartan, an angiotensin II receptor blocker (ARB), selectively blocks the binding of angiotensin II to the AT1 receptor without affecting bradykinin metabolism (which is implicated in ACE inhibitor-induced cough) 4
- In a randomized, double-blind trial specifically studying patients with a history of ACE inhibitor-induced cough, valsartan demonstrated a significantly lower incidence of cough (19.5%) compared to lisinopril (68.9%), with rates similar to hydrochlorothiazide (19.0%) 1
- FDA labeling for valsartan confirms that in clinical trials, the incidence of dry cough was significantly lower in valsartan-treated patients (2.6%) compared to ACE inhibitor-treated patients (7.9%) 5
Clinical Application
- Valsartan is recommended for patients with previous or current symptoms of chronic heart failure with reduced ejection fraction (HFrEF) who are intolerant to ACE inhibitors because of cough or angioedema 2
- The American College of Cardiology/American Heart Association guidelines give a Class 1, Level A recommendation (highest level) for using ARBs like valsartan in patients who cannot tolerate ACE inhibitors due to cough 2
- Valsartan dosing typically starts at 20-40 mg twice daily with titration up to 160 mg twice daily for optimal therapeutic effect 2
Important Considerations
- When switching from an ACE inhibitor to valsartan due to cough, allow at least 36 hours between the last ACE inhibitor dose and starting valsartan to minimize risk of adverse effects 2
- While valsartan has a significantly lower incidence of cough compared to ACE inhibitors, it can still cause cough in a small percentage of patients (2.6% vs. 7.9% with ACE inhibitors) 5
- Monitor for potential side effects of valsartan, including dizziness (most common), hypotension, diarrhea, and hyperkalemia, particularly in patients with renal impairment 5, 4
- Blood pressure, renal function, and potassium levels should be checked within 1-2 weeks after initiation and after any dose changes 2
Special Populations
- Women, non-smokers, and persons of Chinese or East Asian origin have higher risk of ACE inhibitor-induced cough and may particularly benefit from switching to valsartan 2, 3
- Patients with heart failure experience ACE inhibitor-induced cough more frequently than those treated for hypertension alone, making valsartan particularly valuable in this population 2
- In patients with renal insufficiency, valsartan has been shown to be as effective as ACE inhibitors without worsening renal function 6
Pitfalls and Caveats
- Valsartan should not be administered concomitantly with ACE inhibitors or within 36 hours of the last ACE inhibitor dose due to increased risk of adverse effects 2
- While rare, angioedema has been reported with valsartan use, including in some patients who previously experienced angioedema with ACE inhibitors - valsartan should not be re-administered to patients who have had angioedema 5
- Avoid valsartan in pregnancy (FDA pregnancy category D) and in patients with severe hepatic impairment 5
- Although valsartan significantly reduces cough compared to ACE inhibitors, it may not eliminate cough entirely if other underlying causes are present 3