PatientsHCP
This site is for US Health Care Professionals only.
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
Bar chart showing the LS mean change‡ in LVEF over time, measured at baseline, month 6, and month 12.
HFrEF cardiac remodeling measure, showing the LS mean change at 6 months and LS mean change at 12 months.

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‖

*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.2
†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 healthy heart

 

 

 

Cardiac remodeling overview arrows.

 

Cardiac remodeling HFrEF heart

 

 

 

 

Cardiac remodeling overview arrows

 

Cardiac remodeling heart
HEALTHY HEART                                                                                                                                                                                                                                                                                                                             

REMODELED HFrEF HEART1,3-7

  • HFrEF is a clinical syndrome caused by changes in cardiac structure and function
  • These changes can include increased left atrial and ventricular volumes and filling pressure and decreased ejection fraction
  • Cardiac remodeling leads to disease progression and increased risk of CV death and HF hospitalization

REVERSE CARDIAC REMODELING1,3-7

  • Reverse cardiac remodeling changes can include decreased left atrial and ventricular volumes and filling pressure and increased ejection fraction
  • An association has been seen between reverse cardiac remodeling and NT-proBNP reduction                                                                    .

Discover how ENTRESTO patients with HFrEF reported feeling vs enalapril

SEE QUALITY OF LIFE DATA

Read about the effect that ENTRESTO had on hospitalization vs enalapril in HFrEF patients

REVIEW THE DATA

Learn how ENTRESTO impacted hospitalization in HFpEF patients with LVEF below normal* vs valsartan

SEE DATA IN HFpEF

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); HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LAVI, left atrial volume index; LS, least-square; LVEDVI, left ventricular end-diastolic volume index; LVEF, left ventricular ejection fraction; 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. ENTRESTO [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.
3. 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 
4. 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 
5. 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
6. 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
7. 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.