Data Support National Guidelines for ARNI Therapy in Eligible Patients with Heart Failure with Reduced Ejection Fraction Interview with:
Pratyaksh K. Srivastava, MD
Division of General Internal Medicine, UCLA
Gregg C. Fonarow, MD
Ahmanson-UCLA Cardiomyopathy Center
UCLA  Medical Center, Los Angeles
Associate Editor, JAMA Cardiology What is the background for this study? 

Response: Angiotensin Receptor-Neprilysin Inhibitors represent a novel class of heart failure therapeutics that have been shown to significantly improve mortality among patients with heart failure with reduced ejection fraction (HFrEF).

In the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor (ARNI) with Angiotensin Converting Enzyme Inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, sacubitril-valsartan was associated with a 20% relative risk reduction in the primary outcome of death from cardiovascular causes or first hospitalization for worsening heart failure over a median follow up of 27 months.

In our current study, we present long term (5-year) absolute risk reductions associated with the addition of angiotensin receptor-neprilysin inhibition to standard HFrEF background therapy using data from PARADIGM-HF. We utilize the number needed to treat (NNT) to quantify absolute risk reduction, and ultimately compare 5-year NNT values for sacubitril-valsartan to those of well-established HFrEF therapeutics for the outcome of all-cause mortality.  What are the main findings? 

Response: The 5-year NNT with ARNI therapy incremental to ACEi for the outcomes of cardiovascular death/hospitalization for heart failure and all-cause mortality were 14 and 23, respectively. The 5-year NNT values ranged from 13-27 across clinically relevant subpopulations.

Using data from landmark trials, we also calculated 5-year NNT values for traditional HFrEF therapies for the outcome of all-cause mortality. These values were 8 for beta-blockers, 18 for ACEI, 15 for mineralocorticoid antagonists, 14 for implantable cardioverter defibrillator, and 14 for cardiac resynchronization therapy.

These NNT values with ARNI therapy for HFrEF are similar or substantial more favorable than those of other well-accepted, widely used therapy for other cardiovascular diseases. What should readers take away from your report?

Response: Sacubitril-valsartan provides long-term benefits to patients with HFrEF that are incremental to standard background therapies overall and for all clinically relevant subgroups studied. The 5-year NNT values for sacubitril-valsartan are similar to those of well-accepted HFrEF therapies.

These data support current national guideline recommendations for use of ARNI therapy among eligible HFrEF patients. 


The PARADIGM-HF trial was sponsored by Novartis

Pratyaksh K. Srivastava, MD: No Disclosures

Gregg C. Fonarow, MD: Consulting Abbott, Amgen, Bayer, Janssen, Novartis, and Medtronic 


Srivastava PK, Claggett BL, Solomon SD, et al. Estimated 5-Year Number Needed to Treat to Prevent Cardiovascular Death or Heart Failure Hospitalization With Angiotensin Receptor-Neprilysin Inhibition vs Standard Therapy for Patients With Heart Failure With Reduced Ejection FractionAn Analysis of Data From the PARADIGM-HF TrialJAMA Cardiol. Published online November 28, 2018. doi:10.1001/jamacardio.2018.3957 

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Nov 29, 2018 @ 12:26 pm 


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