There are a few important heart failure guideline updates in the works to the American College of Cardiology’s Heart Failure Guidelines, last published in 2013. Prior to the full guideline release, the organization recently printed their updated Expert Consensus Decision Pathway for treatment of patients with heart failure with reduced ejection fraction (HFrEF). This document serves as up-to-date interim guidance until the full guideline is released.

With regard to medications and guideline-directed medical therapy (GDMT), two major changes appear as considerations for patients with Stage C HFrEF (current or prior symptoms) based on data from new studies. (1) The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan is now preferred compared to ACEI/ARBs and (2) sodium-glucose cotransporter-2 inhibitors (SGLT2) are now an option for patients with or without diabetes after ARNI/ACEI/ARB and BB treatment has started. 

Sacubitril/valsartan was previously recommended after a patient in NYHA class II or III was stable on an ACEI/ARB to further reduce morbidity and mortality based on results of the PARADIGM HF trial. New research presented in the PROVE-HF and EVALUATE-HF trials support the preference of ARNIs to ACEI/ARBs even in patients who are naïve to ACEI/ARBs. These new data show safety and efficacy in new populations and notably demonstrated improved heart function by echocardiogram for patients on ARNIs. Remember that for patients previously on an ACE inhibitor, a 36-hour washout period must be utilized before starting an ARNI. The cost of these medications is still a concern and may hinder the ability of all patients to utilize their benefit. When initiating ARNIs in de novo heart failure or transitioning from ACEI/ARB, carefully monitor blood pressure, electrolytes, and renal function as ARNIs are more potent than ACEI/ARBs in terms of blood pressure reduction.

SGLT2 inhibitors have completed their venture from the diabetes space to heart failure treatment. See the Two Diabetes Updates in 2020 that made this HFrEF guideline update expected. Two landmark trials, DAPA-HF and EMPEROR-Reduced (dapagliflozin and empagliflozin, respectively), demonstrated morbidity and mortality benefits in patients with HFrEF in NYHA class II-IV whether or not they had diabetes. The mechanism of action in heart failure for this class of medications is not yet known, but may be due to decreased preload and afterload having beneficial effects on arterial stiffness and cardiac remodeling. As these agents work primarily in the kidney, adequate renal funciton is recommended for their use. Trials with dapagliflozin excluded patients with an eGFR < 30mL/min/1.73m² and empagliflozin excluded those with an eGFR < 20mL/min/1.73m².

The clinician’s toolkit of medications in HFrEF is growing. Many of these agents have shown additive morbidity and mortality benefits on top of the gold-standard ARNI/ACEI/ARB and BB and should be added when possible for patient’s who qualify. See the ACC’s flowchart below for an updated guide to GDMT for stage C HFrEF. Additionally, always remember to check patient’s medication list for drugs to avoid in heart failure!

Have you seen ARNIs used prior to ACEI/ARBs or SGLT2 inhibitors in HFrEF in advance of or since the recent heart failure guideline updates? Comment below!

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Article written by Evan Odean in collaboration with Eric Christianson, PharmD, BCGP, BCPS

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References:

Maddox Thomas M, Januzzi James L, Allen Larry A, et al. 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. JACC 2021;77(6):772-810.

Yancy Clyde W, Januzzi James L, Allen Larry A, et al. 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction. JACC 2018;71(2):201-30.

Yancy Clyde W, Jessup Mariell, Bozkurt Biykem, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC 2017;70(6):776-803.

Yancy Clyde W, Jessup Mariell, Bozkurt Biykem, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation 2013;128:e240-e327.