Optimal use of two recently approved medications for heart failure has been detailed by the major heart societies in a guideline update.

The American College of Cardiology, the American Heart Association, and the Heart Failure Society of America issued joint recommendations May 20 on the two new medicines for stage C heart failure patients with a reduced ejection fraction.

Valsartan/sacubitril (Entresto, Novartis), is a combination angiotensin receptor–neprilysin inhibitor, the first in a novel class of drugs slugged ARNIs. Ivabradine (Corlanor, Amgen), is a sinoatrial node modulator. Both medicines were approved by the Food and Drug Administration in 2015, though ivabradine has been licensed for a decade in Europe.

Although a comprehensive update to ACC/AHA/HSFA heart failure guidelines is still being developed, the focused update is intended to coincide with the release of new European Society of Cardiology heart failure guidelines, “in order to minimize confusion and improve the care of patients with heart failure,” the societies said in a statement May 20. The recommendations were published online simultaneously in Circulation and the Journal of Cardiac Failure.

The guideline authors, led by Dr. Clyde W. Yancy of Northwestern University in Chicago, recommend that the ARNI replace an ACE inhibitor or an angiotensin II receptor blocker (ARB) for patients who have been tolerating these therapies alongside standard care with a beta-blocker and, for some patients, an aldosterone antagonist as well. The guidelines caution against combining an ARNI with an ACE inhibitor, and against using ARNIs in patients with a history of angioedema.

For patients not suited to treatment with an ARNI, continued use of an ACE inhibitor is recommended. In patients for whom an ACE inhibitor or an ARNI is inappropriate, use of an ARB remains advised. The authors noted that head-to-head comparisons of an ARB versus an ARNI for heart failure do not exist; however, in a randomized, controlled trial in heart failure patients, treatment with valsartan/sacubitril plus standard care reduced cardiovascular death or heart failure hospitalization by 20%, compared with treatment with an ACE inhibitor plus standard care.

Ivabradine, meanwhile, has shown benefit in reducing heart failure hospitalizations in patients with symptomatic, stable, chronic heart failure with reduced ejection fraction who are receiving standard treatment including a beta-blocker, and who are in sinus rhythm with a heart rate of 70 beats per minute or greater at rest.

The new therapies, “when applied judiciously, complement established pharmacological and device-based therapies, representing milestones in the evolution of care for patients with heart failure,” wrote Dr. Elliott M. Antman of Brigham and Women’s Hospital and Harvard Medical School in Boston, Mass., in an editorial accompanying the guidelines.

About half the guideline writing committee members and guideline reviewers disclosed financial relationships with pharmaceutical companies or device manufacturers. Dr. Yancy disclosed no conflicts of interest.


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