
PROVE-HF PRIMARY END POINT
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The primary end point was correlation
(Pearson r) between change in echocardiographic
remodeling parameters and NT-proBNP at 12 months†
PROVE-HF PRIMARY END POINT
-
The primary end point was correlation
(Pearson r) between change in echocardiographic
remodeling parameters and NT-proBNP at 12 months†
†P<0.001.
E/e’=filling pressure (early diastolic filling velocity/early diastolic mitral annular velocity); LAVI=left atrial volume index; LVEDVI=left ventricular end-diastolic volume index; LVEF=left ventricular ejection fraction; LVESVI=left ventricular end-systolic volume index.
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).
Patients in the PROVE-HF trial showed reverse cardiac remodeling and biomarker improvement1
ENTRESTO improved key echocardiographic measures of cardiac remodeling, including increased LVEF, and reduced NT-proBNP

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.∥
NT-proBNP=N-terminal prohormone of brain natriuretic peptide.
‡LVEF (%) are median values. Changes in LVEF are LS (least-square) mean change values from baseline.
§LS geometric mean concentration changes from baseline NT-proBNP to follow-up.
∥P<0.001.

PROVE-HF STUDY DESIGN
PROVE-HF study design1
52-week, single-arm, prospective, open-label phase IV evaluation of 794 HFrEF patients in the United States. The primary end point was correlation of change in NT-proBNP to change in cardiac remodeling parameters. At each study visit, a blood sample was sent to a central laboratory for measurement of plasma NT-proBNP. Following completion, echocardiograms were transmitted in a secure fashion to a core laboratory, where they were interpreted following completion of all study protocols in a temporally and clinically blinded fashion.
Key inclusion criteria:
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Aged ≥18 years
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Patients with HFrEF who were candidates for on-label sacubitril/valsartan treatment per the standard of care
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NYHA Functional Class II, III, or IV
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LVEF ≤40% within the preceding 6 months according to any local measurement and no subsequent documentation of EF >40%
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Stable dose of loop diuretic for the 2 weeks preceding study start
Key exclusion criteria:
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History of hypersensitivity/allergy or suspected contraindication to any study drug component or to drugs of similar chemical classes, including ACEis, angiotensin receptor blockers, or neprilysin inhibitors
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Any angioedema history (drug-related or otherwise)
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Concomitant use of ACEi therapy, nesiritide, aliskiren, or drugs that may affect absorption of the study medication
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Current or previous treatment with sacubitril/valsartan
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Inadequate washout of other investigational drugs before study initiation
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Enrollment in another clinical trial within 30 days of screening
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Potassium >5.2 mEq/L at screening
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History of malignancy within 1 year
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Pregnancy, lactation, or use of any method of contraception that is not highly effective
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Implantation of CRT-D within 6 months of screening visit
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Prior heart transplant or left ventricular assist device or intent to implant either
ACEi=angiotensin-converting enzyme inhibitor; CRT-D=cardiac resynchronization therapy defibrillator; EF=ejection fraction; HFrEF=heart failure with reduced ejection fraction; NYHA=New York Heart Association.
PROVE-HF STUDY LIMITATIONS
PROVE-HF study limitations1
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Observational, single-group, open-label design
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A broad range of factors may affect NT-proBNP concentrations besides cardiac remodeling
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Multiple comparisons may have increased risk of type 1 error
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Not all echocardiographic measurements were available at each time point
NT-proBNP=N-terminal prohormone of brain natriuretic peptide.
Reduction in NT-proBNP has been associated with reverse cardiac remodeling1-3
Cardiac remodeling leads to disease progression and increased risk of CV death and heart failure hospitalization in patients with HFrEF4-6
CARDIAC REMODELING OVERVIEW

PARADIGM-HF OVERVIEW AND NT-proBNP ANALYSIS
PARADIGM-HF was a multinational, randomized, double-blind trial comparing ENTRESTO to enalapril in 8442 symptomatic (NYHA Class Il-IV) adult HFrEF patients (LVEF ≤40%). After discontinuing their existing ACEi or ARB therapy, patients entered sequential single-blind run-in periods during which they received enalapril, followed by ENTRESTO. Patients who successfully completed the run-in periods were then randomized to receive either ENTRESTO 97/103 mg (n=4209) twice daily or enalapril 10 mg (n=4233) twice daily. The median follow-up duration was 27 months, and patients were treated for up to 4.3 years.3 For the primary end point, composite of CV death or first heart failure hospitalization, ENTRESTO was superior to enalapril (P<0.0001). In an exploratory analysis, ENTRESTO lowered NT-proBNP by 32% vs 7% with enalapril, compared to baseline (screening), at 4 weeks after randomization.
PARADIGM-HF: NT-proBNP analysis limitations:
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This was a prespecified exploratory end point
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NT-proBNP was analyzed in a subgroup and may not represent the full population
ENTRESTO CV effects are due to increased peptides and decreased angiotensin II effects, which resulted in decreased NT-proBNP.
LVEF=left ventricular ejection fraction; NT-proBNP=N-terminal prohormone of brain natriuretic peptide; NYHA=New York Heart Association.

Discover how ENTRESTO patients reported feeling vs enalapril

Discover how ENTRESTO patients reported feeling vs enalapril
HFrEF=heart failure with reduced ejection fraction.
*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