HFrEF > Hospitalization & Initiation

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PARADIGM-HF: ENTRESTO^® reduced 15-day heart failure readmissions vs enalapril

ENTRESTO demonstrated fewer 15-day heart failure readmissions in a post hoc analysis¹

15-day heart failure readmissions

ARR=absolute risk reduction.
PARADIGM-HF: Readmission was defined as the second hospitalization within 30 days of the first hospitalization after initiation of study drug.

PARADIGM-HF: ENTRESTO reduced 30-day heart failure readmissions vs enalapril

ENTRESTO demonstrated fewer 30-day heart failure readmissions in a post hoc analysis^1,3†‡

30-day heart failure readmissions

ARR=absolute risk reduction. PARADIGM-HF: Readmission was defined as the second hospitalization within 30 days of the first hospitalization after initiation of study drug.¹ ^†Vs enalapril. ^‡Among patients hospitalized at least once for heart failure, patient characteristics were similar at baseline between treatment groups.

PARADIGM-HF PRIMARY END POINT

PARADIGM-HF: Time to first occurrence of CV death or heart failure hospitalization⁵

PARADIGM-Heart Failure: Time to first occurrence of CV death or Heart Failure hospitalization

ARR=absolute risk reduction; CI=confidence interval; HR=hazard ratio; KM=Kaplan–Meier; NNT=number needed to treat; RRR=relative risk reduction.

The median follow-up duration was 27 months and patients were treated for up to 4.3 years.

There was a reduction in each component: CV death 20% RRR, 3.2% ARR; heart failure hospitalization 21% RRR, 2.8% ARR.

PARADIGM-HF was a multinational, randomized, double-blind trial comparing ENTRESTO to enalapril in 8442 symptomatic (NYHA Class II–IV) adult heart failure patients with reduced EF (LVEF ≤40%). After discontinuing their existing ACEi/ARB, patients entered sequential single-blind run-in periods and received enalapril, followed by ENTRESTO. Patients who successfully completed the run-in periods were randomized to ENTRESTO 97/103 mg BID (n=4209) or enalapril 10 mg BID (n=4233).

PARADIGM-HF: HEART FAILURE READMISSIONS ANALYSIS LIMITATIONS

PARADIGM-HF: heart failure readmissions analysis limitations²

This was a post hoc analysis of heart failure readmissions following investigator-reported heart failure hospitalizations; investigator-reported events are vulnerable to misclassification
Patients were not randomized to ENTRESTO or enalapril at the time of index hospitalization; the apparent differences in readmission rate could be attributed to differences in the patients
The primary unit of subsequent analysis was hospitalizations rather than patients
15-day readmissions for heart failure is not a routinely examined time point in quality and clinical assessments, and such early time points may not reflect causality

PIONEER-HF: ENTRESTO reduced 8-week heart failure readmissions vs enalapril

Inpatient initiation of ENTRESTO in stabilized patients resulted in fewer heart failure readmissions^§ at
8 weeks³

8-week heart failure readmissions: prespecified exploratory end point

PIONEER-Heart Failure: ENTRESTO reduced 8-week Heart Failure readmissions vs enalapril

ARR=absolute risk reduction; HR=hazard ratio. ^§PIONEER-HF: Readmission was defined as the first hospitalization after inpatient initiation of study drug.³

PIONEER-HF PRIMARY END POINT

PIONEER-HF was a multicenter, randomized, double-blind, active controlled clinical trial of in-hospital initiation of ENTRESTO (n=440) compared with enalapril (n=441) among heart failure patients with reduced EF (LVEF ≤40%) who had been stabilized following admission for ADHF. At the primary efficacy outcome, time-averaged proportional change in NT-proBNP concentration from baseline through Weeks 4 and 8, ENTRESTO was superior to enalapril (P<0.001).

ADHF=acute decompensated heart failure; EF=ejection fraction; LVEF=left ventricular ejection fraction.

PIONEER-HF: HEART FAILURE READMISSIONS ANALYSIS LIMITATIONS

PIONEER-HF: study limitations³

This was a prespecified exploratory end point; the study was powered for changes in NT-proBNP
Results should be interpreted with caution due to the short time frame and infrequency of events

NT-proBNP=N-terminal prohormone of brain natriuretic peptide.

Get information about starting patients on
ENTRESTO in both outpatient and inpatient settings

INITIATION IN HFrEF

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.⁴

The median time for HFrEF patients to meet the stabilization criteria was less than 3 days after initial presentation to the hospital³

PIONEER-HF STABILIZATION CRITERIA

In PIONEER-HF, hospitalized patients were determined to be stabilized when they met all the following criteria:

BP=blood pressure; IV=intravenous.

ENTRESTO^® was started in the hospital in a diverse set of stabilized HFrEF
patients⁵

Patients enrolled in PIONEER-HF reflect the patients you are likely to treat in your hospital

PIONEER-HF SELECTED DEMOGRAPHIC INFORMATION

PIONEER-Heart Failure SELECTED DEMOGRAPHIC INFORMATION

ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin ‖ receptor blocker.

†Patients were determined to be ACEi/ARB-naive if they were not receiving either medication at the time of index hospitalization.

Whether in the outpatient or inpatient setting, you can start with ENTRESTO across a wide range of patient types^2,5,7

PIONEER-HF: demonstrated safety profile in HFrEF patient initiations.

PIONEER-HF ADVERSE EVENTS

^‡Cardiac failure congestive and acute kidney injury were per investigator discretion on the Case Report Form.

For key safety outcomes, the ENTRESTO group and the enalapril group were generally comparable with regard to rates of worsening renal function, hyperkalemia, symptomatic hypotension, or angioedema⁷
Adverse event profile was comparable to that in the PARADIGM-HF trial^2,5
No new safety signals were observed^2,5
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 duration⁵

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

ENTRESTO IN HFpEF
WITH
LVEF BELOW NORMAL ENTRESTO IN HFpEF
WITH
LVEF BELOW NORMAL

HFpEF=heart failure with preserved ejection fraction; 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.⁴

EXPAND

INDICATION

ENTRESTO is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal.

LVEF is a variable measure, so use clinical judgment in deciding whom to treat.

IMPORTANT SAFETY INFORMATION

WARNING: FETAL TOXICITY

When pregnancy is detected, discontinue ENTRESTO as soon as possible
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus

COLLAPSE

INDICATION

LVEF is a variable measure, so use clinical judgment in deciding whom to treat.

IMPORTANT SAFETY INFORMATION

WARNING: FETAL TOXICITY

When pregnancy is detected, discontinue ENTRESTO as soon as possible
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus

ENTRESTO is contraindicated in patients with hypersensitivity to any component. ENTRESTO is contraindicated in patients with a history of angioedema related to previous angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy.

ENTRESTO is contraindicated with concomitant use of ACE inhibitors. Do not administer within 36 hours of switching from or to an ACE inhibitor. ENTRESTO is contraindicated with concomitant use of aliskiren in patients with diabetes.

Angioedema: ENTRESTO may cause angioedema. Angioedema associated with laryngeal edema may be fatal. ENTRESTO has been associated with a higher rate of angioedema in Black patients and in patients with a prior history of angioedema. ENTRESTO should not be used in patients with hereditary angioedema. If angioedema occurs, discontinue ENTRESTO immediately, provide appropriate therapy, and monitor for airway compromise. ENTRESTO must not be re-administered.

Hypotension: ENTRESTO lowers blood pressure and may cause symptomatic hypotension. Patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those being treated with high doses of diuretics), are at greater risk. Correct volume or salt depletion prior to administration of ENTRESTO or start at a lower dose. If hypotension persists despite dose adjustment of diuretics, concomitant antihypertensive drugs, and treatment of other causes of hypotension (e.g., hypovolemia), reduce the dosage or temporarily discontinue ENTRESTO. Permanent discontinuation of therapy is usually not required.

Impaired Renal Function: Decreases in renal function may be anticipated in susceptible individuals treated with ENTRESTO. In patients whose renal function depends upon the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria, progressive azotemia and, rarely, acute renal failure and death. Closely monitor serum creatinine, and down-titrate or interrupt ENTRESTO in patients who develop a clinically significant decrease in renal function.

ENTRESTO may increase blood urea and serum creatinine levels in patients with bilateral or unilateral renal artery stenosis. In patients with renal artery stenosis, monitor renal function. Avoid use with aliskiren in patients with renal impairment (eGFR <60 mL/min/1.73 m²).

In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors, with ENTRESTO may result in worsening of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically.

Hyperkalemia: Hyperkalemia may occur with ENTRESTO. Monitor serum potassium periodically and treat appropriately, especially in patients with risk factors for hyperkalemia such as severe renal impairment, diabetes, hypoaldosteronism, or a high potassium diet. Dosage reduction or interruption of ENTRESTO may be required.

Concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium, may lead to increases in serum potassium.

ARBs: Avoid use of ENTRESTO with an ARB, because ENTRESTO contains the angiotensin II receptor blocker valsartan.

Lithium: Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists. Monitor serum lithium levels during concomitant use with ENTRESTO.

Common Adverse Events: In a clinical trial of patients with heart failure with reduced ejection fraction, the most commonly observed adverse events with ENTRESTO vs enalapril, occurring at a frequency of at least 5% in either group, were hypotension (18%, 12%), hyperkalemia (12%, 14%), cough (9%, 13%), dizziness (6%, 5%), and renal failure/acute renal failure (5%, 5%). No new adverse reactions were identified in a trial of the remaining indicated population.

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PARADIGM-HF: ENTRESTO® reduced 15-day heart failure readmissions vs enalapril

ENTRESTO demonstrated fewer 15-day heart failure readmissions in a post hoc analysis1