Transcript Related Guidelines

For Patients with HFrEF, What Is the Role for and Treatment Pearls for ARNI?

Javed Butler, MD, MPH, MBA · University of Mississippi


June 11, 2021

Editor’s Note: Results of the phase 4 LIFE study have been shared, in which eligible patients with advanced heart failure were randomized to receive sacubitril/valsartan, the angiotensin-receptor neprilysin inhibitor, or valsartan for 24 weeks. The study showed that sacubitril/valsartan was not superior to valsartan in terms of efficacy, tolerability, or safety profile.[1]

This transcript has been edited for clarity.

The data with angiotensin receptor neprilysin inhibitor (ARNI) therapy, valsartan sacubitril, continue to evolve in terms of its role in the patient’s management with heart failure reduced ejection fraction. Whether or not to initiate a new-onset heart failure patient with valsartan sacubitril, the guidelines have really left it to the clinicians. If you want to start patients with ACE (angiotensin-converting enzyme) inhibitor and then transition to ARNI therapy or whether you initiate a new-onset heart failure patient with ARNI is really a clinician’s choice.[2] Either way, it is fine. What is not fine is to ignore the fact that there was a class 1 recommendation that patients with heart failure reduced ejection fraction who are already on ACE inhibitor and have symptoms, even mild symptoms like class 2, should be switched to ARNI therapy for further reduction in mortality and morbidity.[2] Valsartan sacubitril was shown to reduce the risk of cardiovascular death or heart failure hospitalization.[2] And also, in the secondary analysis of the trials, it improved quality-of-life scores, more so than therapy with ACE inhibitor. So, there is actually a class 1 recommendation that patients on ACE inhibitor or ARB (angiotensin receptor blocker) with persistent symptoms should be switched over to ARNI therapy.[3] 

A few words of caution one, this drug should not be used in combination with ACE inhibitor therapy. So, you don't use it in addition to but instead of ACE inhibitor because of the risk of angioedema. If somebody has angioedema, don't use this drug, or history of angioedema, even if it was mild. But if somebody is on ACE inhibitor, stop ACE inhibitor for 36 hours; let it get it out of the system before starting an ARNI therapy.[3] If somebody is on ARB (angiotensin receptor blocker), however, you can switch right away because you're basically switching one ARB for another and then adding sacubitril or neprilysin inhibitors to their therapy. Follow potassium and follow renal function as you would in patients with an ACE inhibitor or ARB. Some patients may not tolerate high doses. Some patients may require reduction in diuretic doses. Remember that with natriuretic peptide elevation, you do get more natriuretic and the potential for logging depletion. So, a lot of patients may require lower doses of diuretics when we use ARNI therapy as well. If somebody has low blood pressure before compromising on doses of good medical therapy, I would just cut down on the doses of diuretic therapy, give them a little bit more volume, and they may be able to tolerate this therapy. In patients who you are switching from ACE inhibitor or ARB and they're already on moderate doses or high doses, you can start at intermediate doses of ARNI, but somebody who is naive to ACE inhibitor or ARB or is on low doses, then it is prudent to start at low doses of ARNI and slowly go up as tolerated.


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