Sacubitril / Valsartan Label Expansion for Heart Failure Could Significantly Increase Eligible Population

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Under the expanded FDA label, up to 1.8 million people in the United States could be eligible for sacubitril / valsartan, and up to 180,000 events of worsening heart failure (HF) could be prevented or postponed.

The FDA recently extended the label of sacubitril / valsartan for additional use in people with chronic heart failure (HF) with a lower than normal left ventricular ejection fraction (LVEF), which has the potential to ” dramatically increase the population eligible for treatment to 1.8 million people, according to a study published in JAMA Cardiology.

In addition to quantifying the newly eligible candidates for sacubitril / valsartan, the researchers estimated the number needed to treat (NNT) to prevent a worsening of the IC event, as well as the number needed to cause a safety event.

The FDA made the regulatory change based on data from the Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor trial to determine the impact on global mortality and morbidity in heart failure (PARAGON-HF ).

“In particular, in the PARAGON-HF trial, there was a significant interaction between LVEF and treatment efficacy, participants with LVEF at or below the median of 57% appeared to benefit from a greater great clinical benefit ”, explained the authors. “Indeed, the FDA has pointed out that the benefits are more clearly evident in patients with lower than normal LVEF. “

Researchers estimated the prevalence of heart failure using the National Health and Nutrition Examination Survey from 2015 to 2018, then used data from the Get With The Guidelines-Heart Failure (GWTG-HF) registry. American Heart Association to identify the distribution of LVEF in adult patients. who were hospitalized between January 1, 2014 and September 30, 2019.

There were 559,520 hospitalized patients for IC in the GWTG-HF registry who had measurements of LVEF; among these, 45.4% would have met the criteria for the prior indication of sacubitril / valsartan. The new eligibility would make an additional 14 to 39% eligible depending on how the LVEF was viewed. However, they found great variation in the newly eligible population based on 4 ranges of LVEF (45% to 50%, 45% to 55%, 45% to 57% and 45% to 60%).

The 3-year NST in the PARAGON-HF trial was 20 for total hospitalizations for HF, 19 for total hospitalizations for HF and cardiovascular (CV) deaths, and 17 for total worsening of deaths related to CI and CVs. In all LVEF ranges, the expanded FDA label would change the 3-year NNT to:

  • 45% to 50%: 10 for total heart failure hospitalizations, 10 for total heart failure hospitalizations and CV death, and 9 for total worsening of heart failure and cardiovascular deaths
  • 45% -55%: 8 for total heart failure hospitalizations, 8 for total heart failure hospitalizations and CV-related deaths, and 7 for total worsening heart failure and related deaths cardiovascular
  • 45% -57%: 9 for the total number of hospitalizations for heart failure, 9 for the total number of hospitalizations for heart failure and CV death, and 9 for the total worsening of heart failure and death of cardiovascular origin
  • 45% to 60%: 12 for total heart failure hospitalizations, 10 for total heart failure hospitalizations and CV-related deaths, and 10 for total worsening heart failure and related deaths cardiovascular

The 3-year damage requirement, which was not estimated for PARAGON-HF, was estimated to be 20-21 for hypotension due to the FDA label extension.

As a result, the authors estimated that 3 years of treatment with expanded eligibility for sacubitril / valsartan would prevent or delay up to 69,268 (95% CI: 57,558-80,978) worsening events of HF for LVEF from 41% to 50% and up to 182,592 (95% CI, 151,725-213,460) worsening the events of HF for LVEF from 41% to 60%. Extended eligibility over 3 years of treatment would result in up to 32,029 (95% CI: 26,614-37,443) hemodynamic hypotension events for 41% to 50% LVEF and up to 86,164 (95% CI %, 71,598-100,730) hemodynamic hypotension events for LVEF from 41% to 60%.

“In light of the substantial variation in estimates of newly eligible patients with heart failure encompassed by the expanded label, the use of sacubitril / valsartan under real conditions should be carefully monitored,” the authors noted.

Reference

Vaduganathan M, Claggett BL, Greene SJ, et al. Potential implications of expanded US Food and Drug Administration labeling for sacubitril / valsartan in the United States. JAMA Cardiol. 2021; 6 (12): 1415-1423. doi: 10.1001 / jamacardio.2021.3651


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