• New ACC Expert Consensus Decision Pathway includes in-hospital initiation of Entresto following stabilization based on evidence from PIONEER-HF as part of regimen to help improve outcomes for HFrEF patients1
• New ACC Pathway supports the use of Entresto as a first-choice treatment for inpatients and outpatients with HFrEF^1-6

East Hanover, N.J., Sept. 16, 2019 – The American College of Cardiology (ACC) recently published its 2019 ACC Expert Consensus Decision Pathway on Risk Assessment, Management, and Clinical Trajectory of Patients Hospitalized with Heart Failure in the Journal of the American College of Cardiology [2] to provide guidance for improving outcomes and optimizing care for patients hospitalized for heart failure (HF).¹

The new Pathway states that results of the landmark PIONEER-HF trial support the safety of careful initiation of Entresto^® (sacubitril/valsartan), an angiotensin receptor-neprilysin inhibitor (ARNI) in stable heart failure patients with reduced ejection fraction (HFrEF) prior to discharge.¹ In PIONEER-HF, in-hospital initiation of Entresto provided a superior reduction in concentration of an important biomarker at weeks 4 and 8, as compared to enalapril, in stable hospitalized HFrEF patients.^1,2 There were no significant differences in the key safety outcomes of worsening renal function, hyperkalemia, symptomatic hypotension and angiodema.² In a pre-specified exploratory serious clinical composite endpoint, Entresto also showed a greater reduction in the risk of HF re-hospitalization compared to enalapril, complementing previous results in the outpatient setting.^1-3,6 PIONEER-HF is the first and only randomized, controlled, active comparator trial to show positive outcome benefits for hospitalized HFrEF patients.^2,7

Entresto is approved in the U.S. for HFrEF, also known as systolic heart failure, a form of the condition that affects about 50 percent of all HF patients.^8,9 It is a first-choice treatment for HFrEF.^2,4,6

Hospitalization is a serious, yet common, occurrence among people with chronic HF and a hallmark of disease progression.^10-12 HF accounts for approximately 900,000 hospitalizations annually in both men and women—approximately two hospitalizations every minute.¹² The outlook for patients in the first 30 days following HF hospitalization is poor; one in four patients may be re-hospitalized during this time and up to 10 percent may die.^10,11 Hospitalization is a critical time to optimize care, and initiation of HF-specific treatment in the hospital can play an important role in improving outcomes.¹

“Proper in-hospital care is essential for this chronic and progressive condition, and we expect this new Pathway will help reduce the serious burden of heart failure re-hospitalizations and improve outcomes for patients,” said Ricardo Rocha, Vice President and Head of the Cardiovascular, Renal and Metabolic Unit at Novartis. “This Pathway further reinforces the safety and efficacy of in-hospital initiation of Entresto, on top of the already robust data for patients who are not in the hospital.”

This new Pathway adds to the growing body of evidence that supports Entresto’s use in both the inpatient and outpatient setting, which makes it a first-choice treatment for HFrEF patients.^1-6

About Entresto

Entresto (sacubitril/valsartan) is a prescription medicine used to reduce the risk of cardiovascular death and heart failure hospitalization in people with certain types of long-lasting (chronic) heart failure (HFrEF).⁸ Entresto is usually used with other heart failure therapies, in place of an angiotensin-converting enzyme (ACE) inhibitor or other angiotensin II receptor blocker (ARB) therapy.⁸ Entresto is a twice-a-day prescription medicine that works by enhancing the beneficial neurohormonal systems (natriuretic peptide system) while simultaneously inhibiting the harmful effects of the overactive renin-angiotensin-aldosterone system (RAAS).^8,13 Most other heart failure medicines only block the harmful effects of the overactive RAAS. Entresto contains the neprilysin inhibitor sacubitril and the ARB valsartan.⁸ Entresto film-coated tablets are available in three dosage strengths: 24/26 mg, 49/51 mg and 97/103 mg (sacubitril/valsartan).⁸ These doses are referred to as 50 mg, 100 mg and 200 mg in the clinical trial literature including The New England Journal of Medicine publication of the results of PARADIGM-HF.⁷ The target maintenance dose of Entresto is 97/103 mg twice daily as tolerated by the patient.⁸

 

IMPORTANT SAFETY INFORMATION

Entresto can harm or cause death to an unborn baby. Patients should talk to their doctor about other ways to treat heart failure if they plan to become pregnant. If a patient gets pregnant while taking Entresto, she should tell her doctor right away.

Patients are not to take Entresto if they are allergic to sacubitril or valsartan or any of the ingredients in Entresto; have had an allergic reaction including swelling of the face, lips, tongue, throat or trouble breathing while taking a type of medicine called an ACE inhibitor or ARB; or take an ACE inhibitor medicine. Patients are not to take Entresto for at least 36 hours before or after they take an ACE inhibitor medicine. Patients should talk with their doctor or pharmacist before taking Entresto if they are not sure if they take an ACE inhibitor medicine. Patients are not to take Entresto if they have diabetes and take a medicine that contains aliskiren.

Before they take Entresto, patients should tell their doctor about all of their medical conditions, including if they have kidney or liver problems; or a history of hereditary angioedema; are pregnant or plan to become pregnant; are breastfeeding or plan to breastfeed. Patients should either take Entresto or breastfeed. They should not do both.

Patients should tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. They should especially tell their doctor if they take potassium supplements or a salt substitute; nonsteroidal anti-inflammatory drugs (NSAIDs); lithium; or other medicines for high blood pressure or heart problems such as an ACE inhibitor, ARB, or aliskiren.

Entresto may cause serious side effects including serious allergic reactions causing swelling of the face, lips, tongue, and throat (angioedema) that may cause trouble breathing and death. Patients are to get emergency medical help right away if they have symptoms of angioedema or trouble breathing. Patients are not to take Entresto again if they have had angioedema while taking Entresto. People who are black or who have had angioedema may have a higher risk of having angioedema if they take Entresto. Entresto may cause low blood pressure (hypotension). Patients are to call their doctor if they become dizzy or lightheaded, or they develop extreme fatigue. Entresto may cause kidney problems or an increased amount of potassium in the blood.

The most common side effects were low blood pressure, high potassium, cough, dizziness, and kidney problems.

Please see full Prescribing Information, including Boxed WARNING available at http://www.pharma.us.novartis.com/product/pi/pdf/entresto.pdf [3].

Patients are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch [4], or call 1-800-FDA-1088.

Novartis is committed to providing patients with affordable access and resources through Entresto Central. For more information, please call 1-888-ENTRESTO or visit www.entresto.com [5].

 

Disclaimer

This media update contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this media update, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this media update will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political and economic conditions; safety, quality or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this media update as of this date and does not undertake any obligation to update any forward-looking statements contained in this media update as a result of new information, future events or otherwise.

References

1. Hollenberg SM, Stevenson LW, et al. 2019 ACC Expert Consensus Decision Pathway on Risk Assessment, Management, and Clinical Trajectory of Patients Hospitalized with Heart Failure: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.08.001.
2. Velazquez EJ, Morrow DA, DeVore, AD, et al. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med. 2019;380:539-548 doi: 10.1056/NEJMoa1812851.
3. DeVore A, Braunwald E, Morrow D, et al. Initiation of Angiotensin-Neprilysin Inhibition after
   Acute Decompensated Heart Failure: Results of the Open-Label Extension of the PIONEER-HF Trial. Data presented at: American College of Cardiology's 68th Annual Scientific Session, March 16-18; New Orleans, United States.
4. Yancy C, Jessup M, Butler J, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136:e137-161. doi: 10.1161/CIR.0000000000000509.
5. Wachter R, Senni M, Belohlavek J, et al. Initiation of sacubitril/valsartan in hospitalized patients with heart failure with reduced ejection fraction after hemodynamic stabilization: Primary results of the TRANSITION study. Eur Heart J. 2019. doi:10.1002/ejhf.1498.
6. McMurray J, Packer M, Desai A, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004. doi: 10.1056/NEJMoa1409077.
7. Velazquez EJ, Morrow DA, DeVore AD, et al., Rationale and design of the comparison of sacubitril/valsartan versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode (PIONEER-HF) trial. Am Heart J. 2018 Apr;198:145-151. doi: 10.1016/j.ahj.2018.01.004.
8. ENTRESTO [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; November 2018.
9. Savarese G and Lund LH. Global Public Health Burden of Heart Failure. Card Fail Rev. 2017 Apr; 3(1):7-11
10. Dharmarajan K, Hsieh AF, Lin Z, et al., Diagnoses and Timing of 30-Day Readmissions after Hospitalization For Heart Failure, Acute Myocardial Infarction, or Pneumonia. JAMA. 2013;309(4):355-363.
11. Bueno H, Ross JS, Wang Y, et al., Trends in Length of Stay and Short-Term Outcomes among Medicare Patients Hospitalized for Heart Failure: 1993-2008. JAMA. 2010;303(21):2141-2147.
12. Benjamin E, Muntner P, Alonso A, et al. Heart disease and stroke statistics—2019 update: a report from the American Heart Association. Circulation. 2019;139:e56–e66. doi: https://doi.org/10.1161/CIR.0000000000000659 [6].
13. Langenickel T and Dole W. Angiotensin receptor-neprilysin inhibition with LCZ696: a novel approach for the treatment of heart failure. Drug Discov Today. 2012:4: e131-139.

 

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