In HFpEF with LVEF ≤60%,1*
PARAGON-HF: Prescribe ENTRESTO® for more of your patients to reduce heart failure hospitalizations2,3
ENTRESTO reduced total HF hospitalizations and CV death2,3
In a prespecified subgroup analysis of PARAGON-HF patients with LVEF at or below the median (57%)†:
RELATIVE RATE REDUCTION
IN TOTAL HF HOSPITALIZATIONS AND CV DEATH (COMPOSITE END POINT) VS VALSARTAN
RR 0.78 (95% CI: 0.64–0.95); ARR 3.6‡
Driven by reduction in HF hospitalizations
At the primary end point, a composite of total (first and recurrent) HF hospitalizations and CV death, ENTRESTO did not achieve statistical significance vs valsartan (RR 0.87; 95% CI: 0.75–1.01; P=.06).2
ENTRESTO reduced total HF hospitalizations vs valsartan3
Components of the composite end point in patients with LVEF at or below the median (57%)†:
RELATIVE RATE REDUCTION IN
TOTAL HF HOSPITALIZATIONS
RR 0.75 (95% CI: 0.60–0.95); ARR 3.6‡
CV death: HR 0.99 (95% CI: 0.77–1.26); ARR 0.1‡
*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
†LVEF is a variable measure that can change over time, and the normal range differs according to patient characteristics and method of assessment.
‡Event rate per 100 patient-years.
PARAGON-HF composite end point: ENTRESTO reduced the rate of the prespecified exploratory composite end point (total worsening HF events [HF hospitalizations and urgent HF visits] and CV death) by 14% (RR 0.86; 95% CI: 0.75–0.99) compared to valsartan, which was driven by a reduction in the rate of total worsening HF events.
PARAGON-HF NT-proBNP: In a prespecified exploratory analysis, ENTRESTO decreased NT-proBNP from baseline by 24% at Week 16 and 19% by Week 48 compared to decreases of 6% and 3% on valsartan, respectively. NT-proBNP was analyzed in a subgroup and may not represent the full population. ENTRESTO CV and renal effects are due to increased peptides and decreased angiotensin II effects, which result in decreased NT-proBNP.
ENTRESTO® is prescribed across the spectrum of patients from HFrEF to HFpEF with LVEF ≤60%. Learn about the 2023 data from PARAGLIDE-HF1,2,5
PARAGLIDE-HF: THE FIRST AND ONLY HEAD-TO-HEAD STUDY IN STABILIZED HFmrEF AND HFpEF§ PATIENTS FOLLOWING A WORSENING HF EVENT5‖
PARAGLIDE-HF: In the total population, ENTRESTO was superior to valsartan in reduction of NT-proBNP5,7,8
TOTAL POPULATION
ENTRESTO DEMONSTRATED A SIGNIFICANT REDUCTION IN NT-proBNP VS AN ARB AT WEEKS 4 AND 85
PRIMARY END POINT WAS MET: Time-averaged proportional change in NT-proBNP over time from baseline to Weeks 4 and 8
ENTRESTO reduced NT-proBNP by 28% (n=180) compared to 16% with valsartan (n=197), with a proportional difference of 15% (Ratio of change: 0.85; 95% CI: 0.73–0.999; P=.049)
PRESPECIFIED SUBGROUP ANALYSIS: LVEF ≤60%
In PARAGLIDE-HF, the prespecified subgroup analysis was not powered for determining significance of the findings.
PATIENTS ON ENTRESTO HAD A GREATER REDUCTION IN NT-proBNP VS THOSE ON VALSARTAN5,7,8
A decrease in NT-proBNP of >30% from baseline has been associated with a reduced risk of CV death and HF hospitalization9
The sample size was relatively modest. In addition, approximately 19% of patients did not contribute to the primary end point given the lack of NT-proBNP data. Limitations of this analysis are compounded by the inherent limitations when examining subgroups, including reduced sample size, selection bias, multiple comparisons, and lack of power.5
PARAGLIDE-HF: Secondary efficacy end points showed numerical differences favoring patients on ENTRESTO5
In PARAGLIDE-HF, secondary end points were not powered for determining significance of the findings.
The sample size was relatively modest and the study was not powered for clinical events. This study was powered for changes in NT-proBNP. Secondary end points were not powered for determining significance of findings. Results should be interpreted with caution due to the short time frame and infrequency of events. Limitations of this analysis are compounded by the inherent limitations when examining subgroups, including reduced sample size, selection bias, multiple comparisons, and lack of power.5
WIN RATIO (TOTAL POPULATION)
The win ratio numerically favored patients on ENTRESTO vs those on valsartan5
NUMERICALLY FAVORED ENTRESTO
vs valsartan (NS)
Win ratio: 1.19 (95% CI: 0.93–1.52)
Across all components, each pairwise comparison resulted in the following:
- 36.9% of wins were with patients on ENTRESTO
- 31% of wins were with patients on valsartan
- 32.1% of comparisons ended in ties
WIN RATIO (PRESPECIFIED SUBGROUP ANALYSIS: LVEF ≤60%)
In patients with LVEF ≤60%, the win ratio numerically favored patients on ENTRESTO vs those on valsartan5
NUMERICALLY FAVORED ENTRESTO
vs valsartan
Win ratio: 1.46 (95% CI: 1.09–1.95)
Across all components, each pairwise comparison resulted in the following:
- 37.9% of wins were with patients on ENTRESTO
- 26% of wins were with patients on valsartan
- 36.1% of comparisons ended in ties
Wins for individual components:
- Time to CV death: 3.3% with ENTRESTO vs 2.3% with valsartan
- Number and timing of HF hospitalizations: 12.9% with ENTRESTO vs 8.9% with valsartan
- Number and timing of urgent HF visits¶: 2.4% with ENTRESTO vs 1.3% with valsartan
- Change in NT-proBNP: 29% with ENTRESTO vs 20.2% with valsartan
COMPOSITE CV OUTCOMES END POINT (TOTAL POPULATION)
In PARAGLIDE-HF, secondary end points were not powered for determining the significance of the findings.
A numerically reduced rate in a composite end point of total HF hospitalizations, urgent HF visits,¶ and CV death was seen in patients on ENTRESTO vs those on valsartan, driven by reduction in HF hospitalizations.5
17% relative rate reduction in patients on ENTRESTO vs valsartan (NS): RR 0.83 (95% CI: 0.57–1.23); 12.7 ARR#
WORSENING RENAL FUNCTION COMPOSITE END POINT (TOTAL POPULATION)5
In PARAGLIDE-HF, secondary end points were not powered for determining the significance of the findings.
RELATIVE RATE REDUCTION
vs valsartan (NS)
RR 0.62 (95% CI: 0.25–1.56)
34 events were observed with ENTRESTO vs 46 with valsartan
Worsening renal function composite end point was defined as:
- Renal death
- Reaching end-stage renal disease or
- ≥50% decline in eGFR relative to baseline
SAFETY PROFILE
PARAGLIDE-HF: ADVERSE EVENTS OF SPECIAL INTEREST5
No new safety signals were identified5
The exposure-adjusted incidence rates of serious adverse events were 103 (122.2 per 100 patient treatment years) for the ENTRESTO group and 103 (122.2 per 100 patient treatment years) for the valsartan group
There were 18 deaths in the ENTRESTO group (10 CV) and 26 deaths in the valsartan group (18 CV)
Safety data were collected for only 8 weeks; therefore, adverse events that take longer to transpire may not have appeared in this study. Safety information should be interpreted in the context of prior trials with longer duration.5
PARAGLIDE-HF INCLUDED A DIVERSE RANGE OF US AND CANADIAN PATIENTS WHO WERE REFLECTIVE OF THOSE SEEN IN REAL-WORLD PRACTICE5,10,11
In the total patient population,5,7
52% were female
30% were of non-White race/ethnicity (22% were Black)
69.5% were randomized in-hospital following stabilization (30.5% out of hospital)
33% had no prior history of HF
SELECT PATIENT DEMOGRAPHICS5,7
§PARAGLIDE-HF defined HFmrEF and HFpEF as patients with LVEF >40%. The median LVEF was 55%. LVEF is a variable measure that can change over time, and the normal range differs according to patient characteristics and method of assessment.
‖Worsening HF event was defined as an HF hospitalization, emergency department visit, or out-of-hospital urgent HF visit, all requiring IV diuretics.
¶An urgent HF visit was defined as an adjudicated emergency department visit or an urgent clinic visit requiring IV diuretics and not requiring overnight hospitalization.12
#Exposure-adjusted rate per 100 patient-years.
**The worsening renal function adverse event of special interest was defined as an increase in serum creatinine of ≥0.5 mg/L and worsening of the eGFR (mL/min/1.73 m2) by ≥25%.