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Comment & Response
May 4, 2022

Could Neprilysin Be Already Inhibited by BNP in the LIFE Trial?—Reply

Author Affiliations
  • 1Department of Medicine, Washington University School of Medicine, St Louis, Missouri
  • 2MHS Duke Clinical Research Institute, Durham, North Carolina
  • 3Associate Editor, JAMA Cardiology
  • 4TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
JAMA Cardiol. 2022;7(6):657-658. doi:10.1001/jamacardio.2022.0787

In Reply In the LCZ696 in Hospitalized Advanced Heart Failure (LIFE) trial,1 we did not observe a statistically significant difference between sacubitril/valsartan and valsartan with respect to the time-averaged proportional change in the area under the curve (AUC) for N-terminal pro–brain natriuretic peptide (NT-proBNP) levels through 24 weeks of therapy, relative to the baseline levels of NT-proBNP (primary end point), in patients with chronic advanced heart failure with a reduced ejection fraction.1 Based on their prior work, which showed that brain natriuretic peptide (BNP) is an endogenous neprilysin inhibitor when BNP levels exceed 916 pg/mL (to convert to nanograms per liter, multiply by 1),2 Vodovar and colleagues suggest that, in the advanced heart failure population that was studied in the LIFE trial, high circulating levels of BNP may have attenuated the pharmacological differences between sacubitril/valsartan and valsartan by inhibiting sacubitril-mediated degradation of BNP.

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