Real-world data show that Entresto® lowered healthcare costs in patients with heart failure with reduced ejection fraction
Apr 25, 2018
Patients with HFrEF treated with Entresto experienced fewer all-cause hospitalizations, resulting in an average reduction of 28 percent in mean all-cause costs1
East Hanover, N.J., April 25, 2018 – Novartis announced today results from a real-world retrospective cohort study using claims data showing that Entresto® (sacubitril/valsartan), which is indicated in the US to reduce the risk of cardiovascular (CV) death and hospitalization for heart failure (HF), reduced all-cause hospitalizations as well as all-cause healthcare costs.1,2
Key findings included a reduction in mean all-cause costs averaging 28 percent (average cost savings of $1,275 per month per patient) in patients with HF with reduced ejection fraction (HFrEF) treated with Entresto.1 The analysis examined patients on Entresto versus propensity score matched HFrEF patients taking an ACE inhibitor or an angiotensin II receptor blocker (ARB).1 The abstract was published online in the Journal of Managed Care and Specialty Pharmacy.
“The role that Entresto plays in keeping people with heart failure out of the hospital is critical in reducing the health and economic burden associated with this devastating disease,” said Fabrice Chouraqui, President of Novartis Pharmaceuticals Corporation. “This analysis further highlights the need for continued affordable patient access to Entresto.”
“Heart failure is the cause of almost one million hospitalizations each year, or roughly two every minute, and the physical and financial impact of hospitalization on patients, their families and society should not be overlooked,” said study author Nancy Albert, PhD and Associate Chief Nursing Officer, Office of Nursing Research and Innovation, Cleveland Clinic Health System.3 “These findings are consistent with data from clinical trials which established the value of sacubitril/valsartan as a treatment for heart failure that significantly reduced the number of heart failure hospitalizations. This analysis also demonstrated a reduction in overall medical costs.”
Hospitalization for HF costs the U.S. health system more than $16 billion each year.4 About half of all HF is the reduced ejection form of the disease.5 HF is the most common cause of hospitalization in people over 65.6 More than one-quarter of study participants were on a commercial health plan and almost three-quarters were on a Medicare Advantage health plan, which highlights the potential importance of these findings.1
In the study, patients taking Entresto incurred significantly lower all-cause healthcare costs, resulting from a reduction in medical costs that offset an increase in outpatient pharmacy expenses.1 Reductions in HF-related costs were also studied.1
A related abstract was published earlier this month in Circulation: Cardiovascular Quality and Outcomes.7
About the Study Based on real-world data from a large U.S. managed care health plan, consisting of commercial and Medicare Advantage patients, from October 2014 through September 2016, the retrospective study identified 279 HFrEF patients with pharmacy claims for Entresto and propensity score matched these to 279 HFrEF patients with pharmacy claims for ACE inhibitors/ARBs.1 The patient demographics revealed that both cohorts were predominantly male (68.1 percent), with a mean age of 67.9 years.1 The patients also had other comorbidities, including hypertension (90.9 percent), diabetes (56.1 percent) and atrial fibrillation (46.1 percent).1 The findings showed that patients who took Entresto had one heart failure hospitalization per 100 patients per month, compared to three in the ACE inhibitor/ARB group (p=0.003).1 Reductions were also demonstrated for all-cause hospitalizations with patients on Entresto experiencing five hospitalizations per 100 patients per month on average, compared to 11 hospitalizations in the comparator group (p<0.001).1
Patients on Entresto incurred lower mean all-cause costs (representing medical plus outpatient pharmacy costs) than those in the ACE inhibitor/ARB group ($3,220 vs. $4,495 per patient per month, p<0.05), resulting in an average cost saving of $1,275 per patient per month, or an average cost reduction of 28 percent.1 Patients treated with Entresto had higher mean all-cause outpatient pharmacy costs ($947 vs. $515 per patient per month, p<0.001) than those in the ACE inhibitor/ARB group but had lower mean all-cause medical costs ($2,273 vs. $3,980 per patient per month, p<0.05).1 Additional non-statistically significant cost-related findings from the study demonstrated that patients on Entresto also incurred lower HF-related healthcare costs than those in the ACE inhibitor/ARB group ($2,024 vs. $3,088 per patient per month, p=0.059), resulting in an average monthly cost savings of $1,064 per patient.1
Methods Study Design1
This was a retrospective administrative claims study
Study period: October 1, 2014 –September 30, 2016
Study sample: adult commercial or Medicare Advantage health plan enrollees with claims evidence of HFrEF and ≥ 1 claim for SAC/VAL (identified first), ACEI, or ARB from October 1, 2015 –June 30, 2016 (identification period)
Index date: date of first pharmacy claim for SAC/VAL or ACEI/ARB
Baseline period: 12 months prior to the index date
Follow-up period (3-12 months): index date through earliest event of death, end of continuous health plan enrollment, or study end
Variables: patient characteristics, follow-up hospitalization, and follow-up healthcare costs (health plan + patient paid amounts)
Standardized mean differences (SMDs) were calculated to evaluate post-match balance of patient characteristics between cohorts (values ≥ 10% indicate meaningful imbalance)
Robust variance estimation was used to compare hospitalization and healthcare costs between matched cohorts
A multivariable generalized linear model with gamma distribution and log link was used to model follow-up healthcare costs
It is important to note that the nature of this real-world data carries with it some limitations:1
All-cause hospitalization was a pre-specified exploratory endpoint in PARADIGM-HF, the registration trial upon which Entresto’s FDA approval was based.8,9 Cost assessments were not evaluated in PARADIGM-HF.8,9
This study was conducted in a U.S. managed care sample from a specific plan and may not be applicable to other populations or other healthcare plans.1
Pharmacy claims data do not indicate whether patients used medications as prescribed, and do not reflect over-the-counter medications, physician-provided samples, fills not processed through the primary insurer (e.g., medications available through low-cost generic programs), or medications prescribed, but not filled.1
The presence of a diagnosis code on a medical claim does not assure the presence of disease, as diagnoses may be coded incorrectly or included as rule-out criteria.1
Because ejection fraction results are not available in claims data, proxy algorithms were used to help identify patients with HFrEF.1
About Heart Failure Heart failure (HF) is a chronic and progressive condition, which impacts 6.5 million Americans and is the leading cause of hospitalization among Americans over the age of 65.3,6 About half of people with HF have heart failure with reduced ejection fraction (HFrEF), also known as systolic HF.5,10 Reduced ejection fraction means the heart does not contract with enough force, so less blood is pumped out.11 HF presents a major and growing health-economic burden that currently exceeds $30 billion in the United States, which accounts for both direct and indirect costs.4
Novartis has established the largest global clinical program in the HF disease area across the pharma industry to date. Known as FortiHFy, it is comprised of more than 40 active or planned clinical studies designed to generate an array of additional data on symptom reduction, efficacy, quality of life benefits and real-world evidence with Entresto, as well as to extend understanding of heart failure.
About Entresto Entresto® (sacubitril/valsartan) is indicated in the U.S. to reduce the risk of cardiovascular death and hospitalization for heart failure.2 Entresto is usually administered in conjunction with other heart failure therapies, in place of an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB).2 Entresto is a twice-a-day prescription medicine that reduces the strain on the failing heart.2 It does this by enhancing the protective neurohormonal systems (natriuretic peptide system) while simultaneously inhibiting the harmful effects of the overactive renin-angiotensin-aldosterone system (RAAS).2,12 Other heart failure medicines only block the harmful effects of the overactive RAAS.10 Entresto contains the neprilysin inhibitor sacubitril and the angiotensin receptor blocker (ARB) valsartan.2 Entresto film-coated tablets are available in three dosage strengths: 24/26 mg, 49/51 mg, and 97/103 mg (sacubitril/valsartan).2 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. The target maintenance dose of Entresto is 97/103 mg twice daily.2
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 angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (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.
Patients are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, 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.
Disclaimer This press release 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 press release, 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 press release 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; 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 press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
About Novartis Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2017, the Group achieved net sales of USD 49.1 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 124,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com.
References 1. Albert, NM, Swindle, JP, et al. Lower hospitalization and total healthcare costs among patients with heart Failure when treated with sacubitril/valsartan versus angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker: re retrospective study of managed care claims. Poster presentation presented at: Academy of Managed Care Pharmacy Annual Meeting; 2018 April 23-26; Boston, MA. 2. ENTRESTO [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; November 2017. 3. Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation. 2018;137(12):e67-e492. 4. Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013;6:606-619. 5. Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251-259. 6. Weir LM, Pfuntner A, Maeda J, et al. HCUP Facts and Figures: Statistics on Hospital-based Care in the United States, 2009. Agency for Healthcare Research and Quality. 2011;1-3. 7. Albert NM, Swindle JP, et al. Abstract 125: Fewer Hospitalizations And Emergency Room Visits With Sacubitril/Valsartan Versus Angiotensin-Converting Enzyme Inhibitor Or Angiotensin-Receptor Blocker In A Retrospective Claims-Based Study Of Patients With Heart Failure. Circulation: Cardiovascular Quality and Outcomes. 2018;11:A125. 8. McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371 (11):993-1004. 9. Data on file. CSR CLCZ696B2314. Novartis Pharmaceuticals Corp; 2014. 10. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation. 2013;128:e240-e327. 11. Ejection Fraction Heart Failure Measurement. American Heart Association Website. http://www.heart.org/HEARTORG/Conditions/HeartFailure/SymptomsDiagnosisofHeartFailure/Ejection-Fraction-Heart-Failure-Measurement_UCM_306339_Article.jsp (link is external) . Published March 24, 2015. Accessed April 13, 2018. 12. Langenickel T, Dole W. Angiotensin receptor-neprilysin inhibition with LCZ696: a novel approach for the treatment of heart failure. Drug Discov Today. 2012:4: e131-139.