Sacubitril Does Not Cause Dry Cough
Sacubitril/valsartan does not cause dry cough and is actually an excellent alternative for patients who develop ACE inhibitor-induced cough. This is a key clinical advantage that distinguishes it from ACE inhibitors.
Why Sacubitril/Valsartan Does Not Cause Cough
The mechanism explains the difference clearly:
- Sacubitril inhibits neprilysin, which breaks down natriuretic peptides, bradykinin, and other vasoactive substances 1, 2
- Valsartan blocks the angiotensin II receptor (ARB component), not ACE 1, 3
- ACE inhibitors cause cough by preventing the breakdown of bradykinin, leading to its accumulation in the lungs 4
- ARBs do not cause cough because they don't affect bradykinin metabolism through the ACE pathway 4
Clinical Evidence on Cough with Sacubitril/Valsartan
The landmark PARADIGM-HF trial demonstrated that:
- Cough was significantly LESS common with sacubitril/valsartan compared to enalapril (an ACE inhibitor) 5
- The FDA label lists cough as one of the "most common side effects" but at a rate comparable to or lower than ACE inhibitors 1
- Post-marketing surveillance confirms that cough is not a characteristic adverse effect of sacubitril/valsartan 2, 6
Practical Clinical Application
When managing patients with heart failure:
- If a patient develops troublesome cough on an ACE inhibitor (one that stops them from sleeping), European Society of Cardiology guidelines recommend substitution with an ARB 4
- Sacubitril/valsartan is superior to switching to a plain ARB because it provides additional mortality and morbidity benefits beyond simple ARB therapy 7, 3
- The cough must be proven to be ACE inhibitor-induced by demonstrating it recurs after withdrawal and rechallenge 4
Important Caveats
When evaluating cough in heart failure patients:
- Cough is common in heart failure patients due to smoking-related lung disease and other comorbidities 4
- Pulmonary edema must be excluded when new or worsening cough develops, as this is a symptom of decompensated heart failure 4
- Not all ACE inhibitor-induced cough requires discontinuation—only troublesome cough that significantly impacts quality of life 4
Actual Side Effects of Sacubitril/Valsartan
The real adverse effects to monitor include:
- Symptomatic hypotension (most common, more frequent than with ACE inhibitors) 7, 1
- Hyperkalemia (less common than with ACE inhibitors but still requires monitoring) 1, 2
- Worsening renal function (requires serial monitoring of creatinine and eGFR) 1, 6
- Angioedema (rare but serious; higher risk in Black patients and those with prior angioedema) 1, 5