In the PARADIGM-HF trial, sacubitril/valsartan (an ARNI) was compared to enalapril in HFrEF. A KEY safety concern when transitioning a patient from an ACE inhibitor to sacubitril/valsartan is:
- A Hyperkalaemia occurring within 48 hours
- B Significant QT prolongation requiring ECG monitoring
- C Angioedema risk from combined neprilysin inhibition and ACE inhibition; a 36-hour washout period between ACE inhibitor and sacubitril/valsartan is mandatory ✓
- D Neutropenia requiring CBC monitoring weekly
Correct answer: C. Angioedema risk from combined neprilysin inhibition and ACE inhibition; a 36-hour washout period between ACE inhibitor and sacubitril/valsartan is mandatory
Explanation
Neprilysin (neutral endopeptidase) degrades bradykinin. ACE inhibitors also prevent bradykinin breakdown. Combined use of an ACE inhibitor and sacubitril (a neprilysin inhibitor) markedly elevates bradykinin levels, causing a high risk of angioedema. Therefore, a mandatory 36-hour washout period is required when transitioning from any ACE inhibitor to sacubitril/valsartan. Patients with prior ACE inhibitor-induced angioedema should not receive sacubitril/valsartan. This is one of the most tested pharmacological safety points regarding ARNIs.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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