In HFrEF,
PARADIGM-HF: In the largest heart failure (HF) trial ever conducted, ENTRESTO® was superior in keeping patients alive and out of the hospital vs an ACEi1-3
PROVEN RISK REDUCTION IN COMPOSITE END POINT, WITH CONSISTENT RESULTS ACROSS INDIVIDUAL CV DEATH AND HF HOSPITALIZATION COMPONENTS1,2
IN CV DEATH OR HF HOSPITALIZATION AS A FIRST EVENT (COMPOSITE END POINT) VS ENALAPRIL
HR 0.80 (95% CI: 0.73–0.87);
4.7% ARR, P<.0001
NNT: 21
IN CV DEATH†‡ VS ENALAPRIL
3.2% ARR,
NNT: 32
IN FIRST HF HOSPITALIZATION VS ENALAPRIL
2.8% ARR,
NNT: 36
In PARADIGM-HF, 70% of patients were NYHA Class II.1
In an exploratory analysis, ENTRESTO lowered NT-proBNP by 32% vs 7% with enalapril, compared to baseline (screening), at 4 weeks after randomization. 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 result in decreased NT-proBNP.1,4,5
*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.1
†Analyses of the components of the primary composite end point were not prospectively planned to be adjusted for multiplicity.
‡Includes all CV deaths, with or without prior hospitalization.
This was a post hoc analysis of adjudicated death events
Attributing causes of death in clinical trials is especially challenging in cases of suspected sudden cardiac death, and this classification does not necessarily imply a common pathophysiology
Autopsies were available in the minority of cases in PARADIGM-HF
PIONEER-HF: Starting early counts—in-hospital initiation of ENTRESTO reduced heart failure biomarkers and improved outcomes in stabilized patients7,8
29% greater reduction in NT-proBNP from baseline vs enalapril at Weeks 4 and 8.
Ratio of change 0.71 (95% CI: 0.63-0.81); P<.001.7
A decrease in NT-proBNP of >30% from baseline has been associated with reduced risk of CV death and HF hospitalization.5,9
See PIONEER-HF primary end point data below.
ENTRESTO can help your patients with HFrEF stay alive and out of the hospital longer1¶
ENTRESTO reduced the risk of CV death and heart failure readmission vs enalapril in a post hoc analysis8,10#
¶Vs enalapril.
#Readmission was defined as the first hospitalization after inpatient initiation of study drug.
When started in the hospital in stabilized patients, ENTRESTO reduced risk of CV death and HF readmission vs enalapril over 8 weeks.**††
ENTRESTO reduced the risk of CV death and heart failure readmission vs enalapril in a post hoc analysis10**††
**Readmission was defined as the first hospitalization after inpatient initiation of study drug.7
††CV death and heart failure rehospitalizations (8-week, double-blind followed by 4-week, open-label period) events have been adjudicated as defined or probable. A patient is counted only once.
Patients started on ENTRESTO at baseline experienced greater reduction in events vs patients started on enalapril.
PIONEER-HF: CV death or heart failure rehospitalization analyses limitations8
These were post hoc analyses of a composite of retrospectively adjudicated (definite or probable) CV death or heart failure rehospitalization events; the study was powered for changes in NT-proBNP
Weeks 8-12, being open-label, could have an unknowable influence on observed outcomes
Results should be interpreted with caution due to the short time frame and infrequency of events
ENTRESTO delivered rapid and sustained reductions in NT-proBNP vs enalapril4,5
When started in the hospital in stabilized patients, reduction in NT-proBNP was shown as early as Week 1 with ENTRESTO7
A decrease in NT-proBNP of >30% has been associated with reduced risk of CV death and heart failure hospitalization5,9 |
2024 ACC ECDP for HFrEF reinforces the 2022 AHA/ACC/HFSA Guideline: |
‡‡ACEi-treated patients require a 1.5-day washout period before initiating ENTRESTO.
In a real-world analysis within the Cleveland Clinic Health System, ENTRESTO patients had lower heart failure hospitalization rates vs an ACEi/ARB over 6 months13
In addition to demonstrated outcomes from landmark clinical studies, ENTRESTO has gained experience in both real-world inpatient and outpatient settings1,13
Study Methods13
Within a large multistate health care system (OH and FL) with 12 hospitals and over 100 outpatient practices, adult patients prescribed ENTRESTO were matched to patients prescribed an ACEi/ARB
The study cohort was retrospectively identified from August 2015 through July 2018, which preceded the FDA approval of the adult chronic HF indication of ENTRESTO to include HF patients with LVEF below normal in February 2021. The patients identified from these claims data and included in this analysis are considered to reflect the current on-label patient population of ENTRESTO§§
Matching variables: age, sex, and EF%; hospital care vs outpatient care at baseline; index (baseline) date; Charlson Comorbidity Index; systolic blood pressure
HF hospitalizations were compared between the 2 groups
Eligible patients must have had HF and available EF data in the electronic medical record in order to be included
Study Population13
Of 1794 patients who initiated ENTRESTO, 95.1% initiated it in an outpatient department
Baseline mean (SD) age was 64.2 (13.0) years; male: 70.3%
Baseline EFs are shown in the below table
Limitations13
Patients with EF of 40% to 65% are underrepresented (<15%) in the sample identified
Patients were treated in 1 health care system
Medication decisions could have been influenced by system, provider, and patient factors
Patients were not randomized to groups
Nonstudied factors could have influenced findings as is inherent in such retrospective analyses
§§Prior to February 2021, ENTRESTO was indicated for adult patients with HFrEF.
Decrease in rate of HF hospitalization
RELATIVE ODDS REDUCTION in HF hospitalization rate
vs an ACEi/ARB
OR: 0.46 (95% Cl: 0.31-0.67)
3.3% ENTRESTO (n/N=59/1794) vs 6.3% ACEi/ARB (n/N= 112/1794)
These real-world data complement clinical trial data from the PARADIGM-HF and PARAGON-HF clinical trials1,13,14
In PARADIGM-HF, ENTRESTO reduced the risk of HF hospitalization‖‖ in patients with HFrEF by 21% (2.8% ARR) vs enalapril
In PARAGON-HF, ENTRESTO reduced the rate of total HF hospitalization in patients with LVEF at or below the median (57%) by 25% (3.6 ARR¶¶) vs valsartan
‖‖Analyses of the components of the primary composite end point were not prospectively planned to be adjusted for multiplicity.
¶¶Event rate per 100 patient-years.
ARR (PARADIGM-HF), absolute risk reduction; ARR (PARAGON-HF), absolute rate reduction; CI, confidence interval; OR, odds ratio.