Entresto Is Top HFrEF Treatment Recommendation in Updated ACC Guidelines

Treatment optimization for heart failure with reduced ejection fraction (HFrEF) is the focus of the American College of Cardiology (ACC)’s 2021 update to its 2017 Expert Consensus Decision Pathway (ECDP) on managing patients with the condition, published in Journal of the American College of Cardiology.

One focus of the 2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction is optimizing HFrEF treatment through expanded use of Entresto (sacubitril/valsartan; Novartis). It is now recommended ahead of all other renin-angiotensin-aldosterone system (RAAS) inhibitors.

“New therapies for HFrEF have emerged that expand the armamentarium for the treatment of patients with HFrEF since the original Pathway was published in 2017,” noted the ECDP authors in a statement. “As a result, the updated Pathway incorporates two new recommendations for patients with HFrEF, including the up-front use of sacubitril/valsartan without an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker pre-treatment.”

While Entresto, which is part of the angiotensin receptor-neprilysin inhibitor (ARNI) class of HF therapies, is already indicated for use among patients with chronic HF, this update also expands treatment with Entresto to include patients with de novo, or new-onset, HF—a first for the combination neprilysin inhibitor (sacubitril) and angiotensin II receptor blocker (ARB; valsartan).

Concomitant use of Entresto with an angiotensin-converting enzyme (ACE) inhibitor or ARB is contraindicated, however, due to respective risks of angioedema and hypotension, acute kidney injury, and hyperkalemia. To this point, the revised ECDP recommends combination ACE inhibitor/ARB therapy only for patients who are intolerant of Entresto, for whom the RAAS inhibitor is contraindicated, or for those without access to it.

The ARNI class is one of several new treatments—along with sodium-glucose cotransporter-2 inhibitors and percutaneous therapy for mitral regurgitation—that have emerged since the 2017 ECDP to innovate the treatment landscape for HFrEF, noted the authors, prompting the present update.

The ACC report, considered interim guidance, also incorporates “the considerable impact of the coronavirus disease 2019 (COVID-19) pandemic on outpatient management of chronic disease states such as HFrEF,” along with coverage of these 10 fundamental issues:

1. Initiating, adding, or switching to new therapies for HFrEF
2. Achieving optimal therapy
3. Referring patients to an HF specialist
4. Addressing care coordination
5. Improving treatment adherence
6. Addressing specific patient cohorts: African Americans, the elderly, and the frail
7. Managing patients’ medication costs and access
8. Managing complex HF
9. Managing common comorbidities
10. Integrating palliative care and transitioning to hospice care

Additional key points include that ARNIs now top the list of recommended angiotensin antagonists, as well as recommendations to conduct biweekly assessments to reach a solid therapy plan by a maximum of 6 months after HF diagnosis; inform patients of “financially feasible” opportunities such as virtual care when the cost of medications poses a barrier to use, which can lead to adverse patient outcomes; and facilitate team-based care through the use of smart technology.

In seeking to become the first FDA-approved medication to treat patients who have HF with preserved ejection fraction (HFpEF), Entresto went up for a December 2020 vote before the FDA’s Cardiovascular and Renal Drugs Advisory Committee. A 12-1 vote noted there is validity to this recommendation but that data remain inconclusive. At present, Entresto is being investigated in the PARAGLIDE-HF trial to treat HFpEF in patients with acute decompensated HF.

Reference

Maddox TM, Januzzi JL Jr, Allen LA, et al; Writing Committee. 2021 Update to the 2017 ACC Expert Consensus Decision Pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction. J Am Coll Cardiol. Published online January 4, 2021. doi:10.1016/j.jacc.2020.11.022