Pro/Con: Entresto or Standard Therapy for HF?

— Milton Packer, MD and Nancy Sweitzer, MD, squared off on the "best" option for HF

by CardioBrief

Last Updated September 22, 2016
MedpageToday

Editor's Note: Heart failure specialist Eiran Z. Gorodeski, MD (Cleveland Clinic), wrote this account of an important debate on Monday at the Heart Failure Society of America meeting in Orlando.

In a spirited session at the HFSA meeting Milton Packer, MD, of Baylor University Medical Center in Dallas and Nancy Sweitzer, MD, PhD, of the University of Arizona in Tucson debated whether every ambulatory patient with chronic heart failure with reduced ejection fraction (HFrEF) tolerating moderate dose of an ACE inhibitor (ACEI) or angiotensin-receptor blocker (ARB) should, or should not, be switched to the angiotensin-receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (Entresto, Novartis Pharmaceuticals).

Packer, one of the PARADIGM-HF authors, stated provocatively that "no reasonable person who has been awake during the past 2 years should think that this proposition ... is ethically open for debate."

Packer first reminded the audience of HFSA's latest Class I Recommendation that "in patients with chronic symptomatic HFrEF NYHA class II or III who tolerate an ACEI or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality."

Packer then proceeded to explore the question, "why do the latest 2016 updated ACC/AHA/HFSA guidelines recommend switching to ARNI at any dose rather than target dose?" He explained that a majority (approximately 5,500) of patients in PARADIGM-HF were taking medium doses of ACEI or ARB before the trial. Of this subset of the total trial participants, those randomized to ARNI benefited significantly more in terms of reductions in CVD death (see slide provided by Dr. Packer).

Sweitzer came out swinging and landed a punch when she pointed out that " 'everybody' is a very potent word." She reminded Packer, and the audience, of Packer's own words from 2014 describing the types of patients enrolled in PARADIGM-HF, and for whom the findings are generalizable.

Sweitzer then described the case of an 88-year-old (1.44% of PARADIGM patients were ≥85) African American (5% of PARADIGM-HF patients) woman (22% of PARADIGM-HF patients), with non-ischemic cardiomyopathy (40% of PARADIGM-HF) and ejection fraction of 20% (29% of PARADIGM-HF). The patient was on a complex regimen of HF medications including isosorbide mononitrate and hydralazine. She pointed out that managing these medications in the setting of ARNI introduction is unknown. The patient further had colon cancer as a comorbidity, and hospice was being considered. When Sweitzer asked the hypothetical question, "would you switch this patient to Sacubitril-valsartan?", the audience burst out laughing.

The debate was accompanied by discussion on social media. Ryan Daly, MD, (@DrRyanPDaly), a cardiologist from Indianapolis, noted another barrier to transitioning everyone from ACEI to ARNI: "in the real world [it] takes weeks for precertification and approval [by insurance companies]." Another factor that should be mentioned is that a a sizable number of patients won't be able to afford the co-pays, even after their prescription is approved by insurance.