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In the PROVE-HF trial, reduction in NT-proBNP with ENTRESTO® significantly correlated with improvement across measures of cardiac structure and function1

PRIMARY END POINT: Correlation (Pearson r) between change in echocardiographic remodeling parameters and NT-proBNP at 12 months (P<.001)1

  • Functional Measures
    — E/e': r=0.269
    — LVEF: r=-0.381

  • Structural Measures
    — LAVI: r=0.263
    — LVEDVI: r=0.320
    — LVESVI: r=0.405

ENTRESTO improved key echocardiographic measures of cardiac remodeling, including increased LVEF, and reduced NT-proBNP1

Reduction in NT-proBNP was demonstrated at 6 months (35%) and 12 months (37%)

The primary end point was the correlation between change in NT-proBNP and cardiac remodeling parameters at 12 months. A secondary end point was the correlation between change in NT-proBNP and change in cardiac remodeling parameters at 6 months.

Lower yet significant correlations were seen from baseline to 6 months.

In PROVE-HF, over 75% of HF patients were previously on an ACEi/ARB before switching to ENTRESTO1‖

A Pearson correlation coefficient (Pearson r) measures how strong the association is between 2 variables. It ranges from 1 (exactly correlated) to -1 (exactly inversely correlated).
LVEF (%) are median values. Changes in LVEF are LS mean change values from baseline.
§LS geometric mean concentration changes from baseline NT-proBNP to follow-up.
Background medical treatment of study patients at baseline included a beta blocker in 757 patients (95.3%), an ACEi or ARB in 602 (75.8%), and an MRA in 281 (35.4%). Of those not taking ACEi/ARB at baseline, 6% were ACEi/ARB naive, and 18.1% had previously been on but were not currently on ACEi/ARB treatment.

PROVE-HF study limitations1

  • Observational, single-group, open-label design

  • A broad range of factors may affect NT-proBNP concentrations besides cardiac remodeling

  • Multiple comparisons may have increased risk of type 1 error

  • Not all echocardiographic measurements were available at each time point

cardiac remodeling overview


*In PARAGON-HF, defined as LVEF ≥45% with structural heart disease (LAE or LVH); median LVEF was 57%. LVEF is a variable measure and the normal range can vary.7

Important Safety Information


  • When pregnancy is detected, discontinue ENTRESTO as soon as possible
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus

ENTRESTO is contraindicated in patients with hypersensitivity to any component...


ENTRESTO is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal.

LVEF is a variable measure, so use clinical judgment in deciding whom to treat.


ACEi, angiotensin-converting enzyme inhibitor; CRT-D, cardiac resynchronization therapy defibrillator; E/e’, filling pressure (early diastolic filling velocity/early diastolic mitral annular velocity); LAVI, left atrial volume index; LS, least-square; LVEDVI, left ventricular end-diastolic volume index; LVESVI, left ventricular end-systolic volume index; MRA, mineralocorticoid receptor antagonist; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; NYHA, New York Heart Association.

1. Januzzi JL Jr, Prescott MF, Butler J, et al; for the PROVE-HF Investigators. Association of change in N-terminal pro-b-type natriuretic peptide following initiation of sacubitril-valsartan treatment with cardiac structure and function in patients with heart failure with reduced ejection fraction. JAMA. 2019;322(11):1085-1095. doi:10.1001/jama.2019.12821
2. Daubert MA, Adams K, Yow E, et al. NT-proBNP Goal achievement is associated with significant reverse remodeling and improved clinical outcomes in HFrEF. JACC Heart Fail. 2019;7(2):158-168. doi:10.1016/j.jchf.2018.10.014 
3. Weiner RB, Baggish AL, Chen-Tournoux A, et al. Improvement in structural and functional echocardiographic parameters during chronic heart failure therapy guided by natriuretic peptides: mechanistic insights from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study. Eur J Heart Fail. 2013;15(3):342-351. doi:10.1093/eurjhf/hfs180 
4. Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling–concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000;35(3):569-582. doi:10.1016/s0735-1097(99)00630-0
5. Konstam MA, Kramer DG, Patel AR, Maron MS, Udelson JE. Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment. JACC Cardiovasc Imaging. 2011;4(1):98-108. doi:10.1016/j.jcmg.2010.10.008
6. Udelson JE, Konstam MA. Ventricular remodeling fundamental to the progression (and regression) of heart failure. J Am Coll Cardiol. 2011;57(13):1477-1479. doi:10.1016/j.jacc.2011.01.009.
7. ENTRESTO [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.