Updated Heart Failure Guidelines Highlight Role of Entresto, Corlanor

MAY 24, 2016
Michael R. Page, PharmD, RPh
The American College of Cardiology, the American Heart Association, and the Heart Failure Society of America have updated heart failure (HF) guidelines to recommend the use of 2 medications in patients with stage C HF with reduced ejection fraction: the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (Entresto), and the sinoatrial node modulator ivabradine (Corlanor).1,2
According to the guidelines, the recommendation of these 2 medications “represents a milestone in the evolution of care for patients with HF.”1,2
Entresto is now recommended for use in place of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) therapy in patients with HF with reduced ejection fraction. This combination may be used as part of a regimen that includes other HF medications, such as diuretics, aldosterone antagonists, beta-blockers, and isosorbide dinitrate/hydralazine.2,3
In the pivotal phase 3 PARADIGM-HF trial, Entresto was shown to reduce a composite endpoint of cardiovascular death or HF hospitalization by 20% compared with enalapril alone in symptomatic patients with HF and reduced ejection fraction.2,3
The updated guidelines recommend using an ACE inhibitor, ARB, or ARNI in combination with background therapy, including beta-blockers and aldosterone antagonists, to reduce morbidity and mortality. For patients with chronic symptomatic class II or III HF with reduced ejection fraction who tolerate an ACE inhibitor or ARB, the guidelines recommend replacing the existing ACE inhibitor or ARB with an ARNI to reduce morbidity and mortality.2
Importantly, ARNIs should be used instead of ACE inhibitors or ARBs, and not in conjunction with these therapies. Because of the risk of angioedema, patients should not start taking an ARNI within 36 hours of taking their last ACE inhibitor dose.2
Corlanor works by selectively inhibiting the funny channel current of the sinoatrial node. Although a study showed efficacy in reducing a composite of cardiovascular death and HF hospitalization, this benefit was entirely due to reductions in hospitalization rates. However, in the pivotal phase 3 SHIFT trial, approximately three-fourths of patients were not taking an optimum dosage of beta-blocker therapy, which highlights the importance of beta-blocker dosage escalation before initiating Corlanor.2,4
The updated guidelines recommend using Corlanor to reduce the risk of HF hospitalization among patients with NYHA class II or III symptomatic HF and stable, chronic HF with reduced ejection fraction (≤35%) who are receiving background guideline-directed therapy, including a maximally tolerated beta-blocker dosage, and with a heart rate of 70 bpm or higher at rest.2
Key Practice Points for Pharmacists
Pharmacists can implement the following updated guideline recommendations1,2:
·      Recommend the use of Entresto in place of ACE inhibitors or ARBs to provide further morbidity and mortality benefits
·      Ensure that patients starting Entresto do not take the treatment within 36 hours of taking their last ACE inhibitor dose.
·      Ensure that patients starting Entresto do not continue to take their original ACE inhibitor or ARB therapy
·      Recommend uptitration of beta-blocker therapy to a maximally tolerated dose before initiating therapy with Corlanor
·      Ensuring that patients taking Corlanor have a heart rate of 70 bpm or higher at rest before starting therapy

1. American Heart Association [press release]. Societies Release Guideline Update for Heart Failure Therapies Document addresses use of two new heart failure medications. newsroom.heart.org/news/societies-release-guideline-update-for-heart-failure-therapies. Accessed May 20, 2016.
2. 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/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2016.
3. McMurray JJ, Packer M, Desai AS, et al; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004. doi: 10.1056/NEJMoa1409077.
4. Swedberg K, Komajda M, Böhm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376(9744):875-885. 10.1016/S0140-6736(10)61198-1.


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