The number of deaths prevented or postponed for heart failure patients with reduced ejection fraction (HFrEF) may be significantly reduced by initiating angiotensin receptor neprilysin inhibition (ARNI) therapy. Those are the findings of a new analysis which assessed – at population level – the possible benefits of optimal implementation of ARNI therapy.

The researchers used results from the PARADIGM-HF trial which demonstrated superiority in reducing heart failure (HF) deaths with an ARNI, Entresto (sacubitril/valsartan; Novartis), compared to enalapril. The mortality reductions in the trial were expanded and applied to patients in the U.S. with HF, using figures stated by the 2016 American Heart Association Heart Disease and Stroke Statistics Update, with the number needed to treat (NNT) used to gauge the number of potential lives saved per year with ARNI therapy. 

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After exclusions were applied for patients intolerant of ARNI, or those under hospice care, receiving continuous inotropic agents, or needing urgent heart transplantations, the researchers calculated a total of 2,287,296 potential candidates for ARNI therapy.

Their results found that the NNT in order to prevent 1 death was 80.3. For each year, the total number of potentially prevented deaths with optimal ARNI treatment was calculated to 28,484. Sensitivity analysis demonstrated a lower limit of prevented deaths of 18,230 and an upper limit of 41,017.

When it comes to new treatments, some show support for having a time period of 2 to 7 years from first approval to the time when it the therapy is routinely prescribed.

In this instance, based on their results, this stance is questioned by the authors, “There may be substantial downsides in delaying implementation of this new therapy in clinical practice, even if subsequent unforeseen safety issues were to emerge, with potentially tens of thousands of deaths resulting that otherwise could have been prevented or postponed with more timely and complete implementation.”

The author’s acknowledge how their results are based on the premise that the efficacy shown in the PARADIGM-HF treatment translates to a similar degree when applied to HFrEF patients in clinical practice.

Apart from mortality therapy with ARNI has shown other clinical benefits incremental to angiotensin-converting enzyme inhibitor (ACEI) therapy, including reduced hospitalizations and improved health status.

“Given the substantial HF burden and potential benefits of implementation for preventing deaths, efforts to ensure comprehensive implementation of ARNI therapy should be considered,” conclude the authors.

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