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In HFrEF,

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
Is-mean-change

Reduction in NT-proBNP was demonstrated at 6 months (35%) and 12 months (37%)1§

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

Definitions
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.

References
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.