ACC/AHA/ESC Update Heart Failure Guidelines for New Angiotensin Receptor-Neprilysin Inhibitor

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With the release of the angiotensin receptor-neprilysin inhibitor (valsartan/sacubitril) and a sinoatrial node modulator (ivabradine), AHA/ACC/ESC have updated heart failure therapy guidelines.

The American College of Cardiology (ACC), American Heart Association (AHA), and European Society of Cardiology (ESC), in collaboration with the Heart Failure Society of America (HFSA) and the Heart Failure Association (HFA) of the ESC, have released updates on 2 practice guidelines concerning the pharmacological management of HF.

The multi-organizational recommendations were produced in response to 2 new HF medications: the angiotensin receptor-neprilysin inhibitor (ARNI; valsartan/sacubitril) and a sinoatrial node modulator (ivabradine). The resulting document was published simultaneously in the Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure.

In patients with chronic HF with reduced ejection fraction (HFrEF), inhibition of the renin-angiotensin system with ACE (angiotensin-converting enzyme) inhibitors or angiotensin receptor blockers (ARB) or ARNI in conjunction with evidence-based beta blockers, and aldosterone antagonists in selected patients, is recommended to reduce morbidity and mortality (class of recommendation [COR]: I; level of evidence [LOE]: A for ACE, A for ARB, and B-R for ARNI).

The authors noted that in a randomized clinical control trial that compared the ARNI, valstartan/sacubitril, with enalapril in HFrEF patients who tolerated an adequate dose of either an ACE inhibitor or ARB, the ARNI reduced cardiovascular death or HF hospitalization by 20%.

In addition, ARBs are recommended in patients with prior or current symptoms of chronic HFrEF who are ACE inhibitor-intolerant due to cough or angioedema (COR: I; LOE: A). The authors also recommended replacement by an ARNI in patients with chronic symptomatic HFrEF with New York Heart Association (NYHA) class II or III who can tolerate an ACE inhibitor or ARB to further reduce morbidity and mortality (COR: I; LOE: B-R).

Conversely, ARNI should not be administered concomitantly with an ACE inhibitor within 36 hours of the last ACE inhibitor dose (class of recommendation: III, harm; level of evidence: B-R), nor should it be administered to patients with a history of angioedema (COR: III, harm; LOE: C-EO).

Ivabradine, specifically, can reduce HF hospitalizations and therefore is recommended in patients with symptomatic, stable chronic NYHA class II-III HFrEF with left ventricular ejection fraction ≤35% who are currently receiving guideline-directed evaluation and management (including a beta blocker at maximum tolerated dose) and are in sinus rhythm with a heart rate of 70 beats per minute or greater at rest (COR: IIa, LOE: B-R).

In an accompanying editorial to these guideline updates, ACC/AHA task force members and writing committee members wrote, “Each writing committee surveyed the evidence independently and constructed similar recommendations, which were then shared between the organizations. Given the robust processes used by both expert writing committees … the organizations agreed to publish them concurrently to unify the message, minimize confusion, and improve and standardize the care of patients with heart failure.”


  1. Antman EM, Bax J, Chazal RA, et al. Updated clinical practice guidelines on heart failure: an international alignment. J Am Coll Cardiol. 2016. doi:10.1016/j.jacc.2016.05.012.
  2. Yancy CW, Jessup M, Bozkurt B, et al; on behalf of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. 2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2016. doi:10.1016/j.jacc.2016.05.011.