US and European Heart Failure Guidelines Advocate Use of Two New Therapies

Both the American and the European practice guidelines for the management of patients with chronic heart failure have been updated to incorporate two new therapies that have been creating a buzz in the heart failure arena for the last year. 

Take Home. US and European Heart Failure Guidelines Advocate Use of Two New Therapies

“The introduction of an angiotensin receptor-neprilysin inhibitor (ARNI), valsartan/sacubitril, and a sinoatrial node modulator, ivabradine, when applied judiciously, complement established pharmacological and device-based therapies, representing milestones in the evolution of care for patients with heart failure,” write Elliott M. Antman, MD (Brigham and Women’s Hospital, Boston, MA), and colleagues in an editorial accompanying the newly published American guidelines, which were published on May 20, 2016, in the Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure. The European guidelines were released concurrently at the start of a heart failure congress in Italy.

When ivabradine (Corlanor; Amgen) was approved by the US Food and Drug Administration (FDA) in 2015, it became the first new drug to be approved for heart failure in almost a decade. The approval was based on results from the SHIFT trial comparing the drug with placebo in 6,558 patients. Patients given ivabradine had a lower risk of the combined endpoint of hospitalization for worsening heart failure or CV death based on a time-to-event analysis (HR 0.82, 95% CI 0.75-0.90).

Similarly, the ARNI valsartan/sacubitril (Entresto; Novartis) was approved by the FDA in July 2015 on the strength of data from the PARADIGM-HF trial, which showed that compared with the ACE inhibitor enalapril, it was associated with a lower rate of CV death or HF hospitalization (HR 0.80; 95% CI 0.73-0.87).

The updated guidelines now recommend an ACE inhibitor, ARB, or ARNI along with a beta blocker and an aldosterone antagonist for patients with chronic symptomatic heart failure with reduced ejection fraction. They state that ARNIs should replace ACE inhibitors (or ARBs) when stable patients with mild-to-moderate heart failure on these therapies have an adequate blood pressure and are otherwise tolerating standard therapies well. ARNIs, however, are not meant for use with an ACE inhibitor (or within 36 hours of an ACE inhibitor) or for patients with a history of angioedema.

As for ivabradine, the US guideline writing committee, chaired by Clyde W. Yancy, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), says it may be beneficial in reducing HF hospitalizations in patients with symptomatic stable chronic heart failure with reduced ejection fraction who are receiving guideline-directed evaluation and management, including a beta blocker at a maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 beats per minute or greater at rest.

“Given the well-proven mortality benefits of beta-blocker therapy, it is important to initiate and up titrate these agents to target doses, as tolerated, before assessing the resting heart rate for consideration of ivabradine initiation,” the guideline update states.

Although the complete focused update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure is still in development and is expected within the next year, the organizations said in a press release that they were releasing these recommended changes early to coincide with the European guideline update “in order to minimize confusion and improve the care of patients with heart failure.”


  • Yancy reports no relevant conflicts of interest. 
  • The editorial contains no disclosure information for Antman. 

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  • Yancy CW, Jessup M, Bozkurt B, et al. 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;Epub ahead of print.

  • Antman EM, Bax J, Chazal RA, et al. Updated clinical practice guidelines on heart failure: an international alignment. J Am Coll Cardiol. 2016;Epub ahead of print.