2022 Heart Failure Guideline

The 2022 AHA/ACC/HFSA Heart Failure Guideline recognizes ENTRESTO® in three heart failure patient populations1†

HFrEF LVEF ≤40%

  • HFrEF LVEF ≤40%

  • HFmrEF LVEF 41%-49%

  • HFpEF LVEF ≥50%

The 2022 AHA/ACC/HFSA Heart Failure Guideline recognizes ENTRESTO® in three heart failure patient populations1†

HFrEF
LVEF ≤40%

HFmrEF
LVEF 41%-49%

HFpEF
LVEF ≥50%

Patients with LVEF below normal who may be appropriate for ENTRESTO2

HFrEF: The Heart Failure Guideline recommends ENTRESTO to reduce morbidity and mortality‡

‡NYHA class II/III patients with HFrEF.

START

YOUR NEWLY DIAGNOSED
PATIENTS WITH THE

PREFERRED RASi

Class 1 recommendation as a
FIRST-LINE TREATMENT and
PREFERRED INSTEAD OF ACEi/ARB1

Class 1 recommendation as a FIRST-LINE TREATMENT and PREFERRED INSTEAD OF ACEi/ARB1

SWITCH

YOUR EXISTING
ACEi/ARB PATIENTS

NOW

Class 1 recommendation to REPLACE ACEi/ARB1§

Class 1 recommendation to REPLACE ACEi/ARB1§

§In patients who tolerate ACEi/ARB.

ENTRESTO is the ONLY BRANDED HEART FAILURE MEDICATION
 deemed by the Heart Failure Guideline to provide HIGH ECONOMIC VALUE1‖

In patients with chronic symptomatic HFrEF, treatment with ENTRESTO instead of an ACEi provides HIGH ECONOMIC VALUE

Multiple analyses found ENTRESTO to be HIGH VALUE compared to an ACEi in the outpatient setting

Inpatient initiation of ENTRESTO was seen as HIGH VALUE compared with delayed initiation post-discharge

‖Value statements for select therapies were created based upon benchmarks adopted by AHA/ACC/HFSA where high-quality cost-effectiveness studies of the intervention had been published.

SEE THE 2022 HEART FAILURE GUIDELINE

See how the Heart Failure Guideline recognizes ENTRESTO
for select HFmrEF patients, particularly for patients
with LVEF on the lower end of this spectrum1,2

HFmrEF
(LVEF 41%-49%) HFmrEF
(LVEF 41%-49%)

†In the 2022 Heart Failure Guideline, ENTRESTO is recommended as a first-line treatment and to replace well-tolerated ACEi/ARB in patients with HFrEF. ENTRESTO was also included as a treatment option for HFmrEF (LVEF 41%-49%) and selected patients with HFpEF (LVEF ≥50%), particularly for patients with LVEF on the lower end of these spectrums.
*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
ACC=American College of Cardiology; ACEi=angiotensin-converting enzyme inhibitor; AHA=American Heart Association; ARB=angiotensin II receptor blocker; HFmrEF=heart failure with mildly reduced ejection fraction; HFpEF=heart failure with preserved ejection fraction; HFrEF=heart failure with reduced ejection fraction; HFSA=Heart Failure Society of America; LAE=left atrial enlargement; LVEF=left ventricular ejection fraction; LVH=left ventricular hypertrophy; MRA=mineralocorticoid receptor antagonist; NYHA=New York Heart Association; RASi=renin-angiotensin system inhibitor.

Patients with LVEF below normal who may be appropriate for ENTRESTO2

The 2022 Heart Failure Guideline expands its recognition of ENTRESTO to select HFmrEF patients1

HFmrEF

Consider ENTRESTO in HFmrEF to reduce the risk of HEART FAILURE HOSPITALIZATION AND CV MORTALITY, particularly for patients with LVEF on the lower end of this spectrum.1

Consider ENTRESTO in HFmrEF to reduce the risk of HEART FAILURE HOSPITALIZATION AND CV MORTALITY, particularly for patients with LVEF on the lower end of this spectrum.1

SEE THE 2022 HEART FAILURE GUIDELINE

See how the Heart Failure Guideline recognizes ENTRESTO for select HFpEF patients, particuarly for patients with LVEF on the lower end of this spectrum1,2

HFpEF
(LVEF ≥50%) HFpEF
(LVEF ≥50%)

†In the 2022 Heart Failure Guideline, ENTRESTO is recommended as a first-line treatment and to replace well-tolerated ACEi/ARB in patients with HFrEF. ENTRESTO was also included as a treatment option for HFmrEF (LVEF 41%-49%) and selected patients with HFpEF (LVEF ≥50%), particularly for patients with LVEF on the lower end of these spectrums.
*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
ACC=American College of Cardiology; ACEi=angiotensin-converting enzyme inhibitor; AHA=American Heart Association; ARB=angiotensin II receptor blocker; CV=cardiovascular; HFmrEF=heart failure with mildly reduced ejection fraction; HFpEF=heart failure with preserved ejection fraction; HFrEF=heart failure with reduced ejection fraction; HFSA=Heart Failure Society of America; LAE=left atrial enlargement; LVEF=left ventricular ejection fraction; LVH=left ventricular hypertrophy.

Patients with LVEF below normal who may be appropriate for ENTRESTO2

The 2022 Heart Failure Guideline expands its recognition of ENTRESTO to select HFpEF patients1

SELECT PATIENTS WITH


HFpEF

Consider ENTRESTO in HFpEF to decrease
HEART FAILURE HOSPITALIZATIONS,2‡ particularly for patients with LVEF on the lower end of this spectrum.1

†In the 2022 Heart Failure Guideline, ENTRESTO is recommended as a first-line treatment and to replace well-tolerated ACEi/ARB in patients with HFrEF. ENTRESTO was also included as a treatment option for HFmrEF (LVEF 41%-49%) and selected patients with HFpEF (LVEF ≥50%), particularly for patients with LVEF on the lower end of these spectrums.
‡PARAGON-HF was a randomized, double-blind, active-controlled trial comparing ENTRESTO to valsartan in 4796 adult patients with symptomatic (NYHA Class II–IV) HFpEF ≥45%, elevated levels of natriuretic peptides, and structural heart disease. After completing the run-in period with valsartan followed by ENTRESTO, patients entered the double-blind period and were randomly assigned (1:1) to ENTRESTO 97/103 mg BID (n=2407) or valsartan 160 mg BID (n=2389). The median follow-up duration was 35 months, and patients were treated for up to 4.7 years. At the primary end point, reduction in the 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=0.06).2

SEE THE 2022 HEART FAILURE GUIDELINE

See the ACC Expert Consensus Decision Pathway
recommendation of ENTRESTO for select HFrEF patients

ACC ECDP UPDATE

*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
ACC=American College of Cardiology; ACEi=angiotensin-converting enzyme inhibitor; AHA=American Heart Association; ARB=angiotensin II receptor blocker; ARR=absolute rate reduction; CI=confidence interval; CVD=cardiovascular death; ECDP=Expert Consensus Decision Pathway; HFH=heart failure hospitalization; HFmrEF=heart failure with mildly reduced ejection fraction; HFpEF=heart failure with preserved ejection fraction; HFrEF=heart failure with reduced ejection fraction; HFSA=Heart Failure Society of America; LAE=left atrial enlargement; LVEF=left ventricular ejection fraction; LVH=left ventricular hypertrophy; RR=relative rate.

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

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

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.

Click here for full Prescribing Information,
including Boxed WARNING.

References:

1. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(17):e263-e421. doi:10.1016/j.jacc.2021.12.012 2. ENTRESTO [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.

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