Prevention of Life-Threatening Angioedema with ARNI Therapy

Introduction to ARNI Therapy

The American College of Cardiology recommends a mandatory 36-hour washout period when switching from an ACE inhibitor to an ARNI to prevent potentially fatal angioedema, with a Class III: Harm recommendation for non-adherence 1, 2, 3

Both ACE inhibitors and neprilysin inhibitors block the breakdown of bradykinin through different pathways, and dual blockade of both pathways simultaneously causes dangerous accumulation of bradykinin, triggering angioedema 1
ACE inhibitors prevent bradykinin degradation by blocking angiotensin-converting enzyme, while neprilysin inhibitors prevent bradykinin breakdown by blocking the neprilysin enzyme 1

When switching from an ACE inhibitor to an ARNI, the American College of Cardiology recommends stopping the ACE inhibitor completely and waiting exactly 36 hours before administering the first dose of ARNI, with a mandatory and non-negotiable washout period 1, 2, 3
The American College of Cardiology recommends considering longer washout periods in patients with a history of angioedema, though specific duration is not defined 5
When switching from an ARB to an ARNI, no washout period is required, as ARBs do not block bradykinin breakdown through the same mechanism as ACE inhibitors 2, 3

Patients should be educated about early signs of angioedema, such as facial swelling, tongue swelling, and difficulty breathing, and monitored for these symptoms during the transition 4
Blood pressure should be monitored within 1-2 weeks after the switch, and renal function and potassium should be reassessed within 1-2 weeks, according to the American College of Cardiology guidelines 2
Volume status should be optimized before initiating ARNI to minimize hypotension risk, as recommended by the American College of Cardiology 2

The 36-hour washout rule is not required when simply switching from an ACE inhibitor to a standard ARB without neprilysin inhibition, but monitoring for angioedema remains prudent given 2-17% cross-reactivity risk 5
ARNI should never be administered concomitantly with ACE inhibitors, as dual blockade of the renin-angiotensin system is potentially harmful and should be avoided, according to the American Heart Association and American College of Cardiology guidelines 1, 6