Chronic HF is a progressive disease that puts patients at risk

Heart failure is deadlier than many cancers, MI, and stroke1-3

5-Year Cancer Death Rates, Chart
 
5-Year Comorbidity Death Rates, Chart
*≥45 years of age.

Even your patients with mild symptoms are at risk

Landmark studies demonstrated that ~1 in 4 NYHA Class II patients experienced poor outcomes4,5

29% of Patients, CV Death or HF Hospitalization
of mildly symptomatic (NYHA Class II) patients died from CV causes or were hospitalized for HF
in CHARM, a 2003 clinical trial of NYHA Class II-IV HF with a median follow-up of ~3.3 years4†
22% of Patients, CV Death or HF Hospitalization
of mildly symptomatic (NYHA Class II) patients died from CV causes or were hospitalized for HF
in EMPHASIS, a 2011 clinical trial of patients with NYHA Class II HF that had a median follow-up of 21 months5‡

The majority of HF patients have mild to moderate symptoms

61% of systolic HF patients are considered NYHA Class II or III6

Patients by NYHA Class, Chart
Class I
No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea (shortness of breath).
Class II
Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, or dyspnea.
Class III
Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea.
Class IV
Unable to carry on any physical activity without symptoms of HF. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.
§Based on data from the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) in participants with diagnosed HF and reduced LVEF (≤35%) or prior MI and reduced LVEF in outpatient cardiology practices.
MI=myocardial infarction; NYHA=New York Heart Association; CV=cardiovascular; LVEF=left ventricular ejection fraction; ACE=angiotensin-converting enzyme.
The CHARM low left ventricular ejection fraction (LVEF) trials were two randomized, parallel, placebo-controlled trials (CHARM-Alternative, for patients who cannot tolerate ACE inhibitors, and CHARM-Added, for patients who were receiving ACE inhibitors). Mortality and morbidity were determined in 4576 low (≤40%) LVEF patients (2289 receiving candesartan and 2287 receiving placebo), titrated as tolerated to a target dose of 32 mg once daily, and observed for 2 to 4 years (median, 40 months). The primary outcome (time to first event by intention to treat) was cardiovascular death or heart failure hospitalization for each trial, in the pooled analysis of the low LVEF trials.4
EMPHASIS was a randomized, double-blind, placebo-controlled trial of 2737 patients with an LVEF ≤35% and at least 55 years of age. Patients received eplerenone (up to 50 mg daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure.5

INDICATION

ENTRESTO is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.

ENTRESTO is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB.

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, 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%).

Click here for full Prescribing Information, including Boxed WARNING.

References: 1. Roger VL, Weston SA, Redfield MM, et al. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004;292(3):344-350. 2. Howlader N, Noone AM, Krapcho M, et al (eds). SEER Cancer Statistics Review, 1975-2013, National Cancer Institute. Bethesda, MD. https://seer.cancer.gov/csr/1975_2013. Accessed November 29, 2016. Based on November 2015 SEER data submission, posted to the SEER website, April 2016. 3. Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart disease and stroke statistics—2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146-e603. 4. Young JB, Dunlap ME, Pfeffer MA, et al. Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction results of the CHARM low-left ventricular ejection fraction trials. Circulation. 2004;110(17):2618-2626. 5. Zannad F, McMurray JJV, Krum H, et al. Eplererone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11-21. 6. Fonarow GC, Albert NM, Curtis AB, et al. Improving evidence-based care for heart failure in outpatient cardiology practices: primary results of the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF). Circulation. 2010;122(6):585-596.

References: 1. Roger VL, Weston SA, Redfield MM, et al. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004;292(3):344-350. 2. Howlader N, Noone AM, Krapcho M, et al (eds). SEER Cancer Statistics Review, 1975-2013, National Cancer Institute. Bethesda, MD. https://seer.cancer.gov/csr/1975_2013. Accessed November 29, 2016. Based on November 2015 SEER data submission, posted to the SEER website, April 2016. 3. Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart disease and stroke statistics—2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146-e603. 4. Young JB, Dunlap ME, Pfeffer MA, et al. Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction results of the CHARM low-left ventricular ejection fraction trials. Circulation. 2004;110(17):2618-2626. 5. Zannad F, McMurray JJV, Krum H, et al. Eplererone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11-21. 6. Fonarow GC, Albert NM, Curtis AB, et al. Improving evidence-based care for heart failure in outpatient cardiology practices: primary results of the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF). Circulation. 2010;122(6):585-596.

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION

ENTRESTO® is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II–IV) and reduced ejection fraction.

INDICATION

ENTRESTO® is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II–IV) and reduced ejection fraction.

ENTRESTO is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB.

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, 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%).

Tap here for full Prescribing Information, including Boxed WARNING.