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Boehringer Ingelheim: Initial results from EMPRISE real-world evidence study
- Empagliflozin was associated with a 44 percent reduction in relative risk of hospitalization for heart failure (HHF) compared with commonly used dipeptidyl peptidase-4 inhibitors1
- Effect of empagliflozin on HHF was consistent in patients with and without established cardiovascular disease1
- Findings support data from the landmark EMPA-REG OUTCOME® trial, in which empagliflozin reduced the relative risk of HHF by 35 percent in people with type 2 diabetes and established cardiovascular disease2
Initial effectiveness results from the real-world EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study showed empagliflozin was associated with a 44 percent relative risk reduction in hospitalisation for heart failure (HHF) compared with dipeptidyl peptidase-4 (DPP-4) inhibitors in routine clinical practice in the U.S. The EMPRISE analysis of data from approximately 35,000 people with type 2 diabetes between August 2014 and September 2016 will be presented at the American Heart Association® (AHA) Scientific Sessions 2018 in Chicago, Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced.
These results support findings from the EMPA-REG OUTCOME® trial, which showed a 35 percent relative risk reduction in HHF (a secondary endpoint) with empagliflozin, compared with placebo, when added to standard of care, in people with type 2 diabetes and established cardiovascular disease.1,2
“With more than a million hospital admissions for heart failure in the U.S. every year, it’s important to understand whether the relative risk reduction in hospitalisation for heart failure seen in the EMPA-REG OUTCOME trial translates into routine clinical care,” said Elisabetta Patorno, M.D., DrPH, of the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Assistant Professor of Medicine, Harvard Medical School, and study co-investigator. “These first results from the EMPRISE study show that empagliflozin is associated with a reduction in hospitalisation for heart failure, and the effect is consistent in people with type 2 diabetes with and without history of cardiovascular disease.”
The full EMPRISE real-world evidence study will provide a clinical picture of empagliflozin in routine clinical care including comparative effectiveness, safety and healthcare resource utilisation and cost outcomes compared with commonly used DPP-4 inhibitors between 2014 and 2019. Early findings from EMPRISE, which at completion will assess the first five years of empagliflozin use in the U.S. through 2019, represent data collected between August 2014 and September 2016. The effectiveness findings will be updated as more data are gathered. Safety data from EMPRISE are not yet available and will be presented at a future time. EMPRISE was initiated, and is being led by academic partners from the Division of Pharmacoepidemiology at Brigham and Women’s Hospital and Harvard Medical School. The study is part of an academic collaboration between Brigham and Women’s Hospital and Boehringer Ingelheim.
“Insights from the EMPRISE real-world evidence study are critical in today’s healthcare landscape to understand how gold standard clinical trials, such as the EMPA-REG OUTCOME® trial, can reduce the burden of cardiovascular disease in patients seen in everyday clinical practice,” said Waheed Jamal, MD, Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “Initial results from EMPRISE suggest that, compared with DPP-4 inhibitors, empagliflozin provides cardioprotective benefits in people with type 2 diabetes with and without cardiovascular disease.”
By study completion, EMPRISE is expected to have analysed health records of more than 200,000 people with type 2 diabetes from two commercial U.S. healthcare providers and Medicare. From 2019, additional EMPRISE studies including Asia and Europe will provide insights from different regions of the world with an international perspective on the use of empagliflozin in routine clinical care.
“The Boehringer Ingelheim and Lilly Diabetes Alliance is committed to building a comprehensive clinical picture of empagliflozin across the cardiovascular risk continuum in type 2 diabetes,” stated Sherry Martin, M.D., vice president, Medical Affairs, Lilly Diabetes. “Physicians need better options to help their patients avoid hospitalisation for heart failure, and we are encouraged that these findings from EMPRISE complement cardiovascular results from the EMPA-REG OUTCOME® trial. We are committed to further understanding whether empagliflozin may have potential in this area and look forward to sharing the future results of the EMPRISE study.”
As part of their efforts to help address unmet needs, Boehringer Ingelheim and Lilly have initiated two large clinical trial programs focused on improving outcomes and reducing morbidity and mortality for people with heart failure. EMPEROR HF comprises two Phase III outcome trials investigating empagliflozin for the treatment of adults with chronic heart failure. The trials include not only adults with type 2 diabetes who have heart failure, but also people with heart failure who do not have diabetes.3,4 EMPERIAL comprises two Phase III studies evaluating the effect of empagliflozin on exercise ability and heart failure symptoms in people with chronic heart failure with or without type 2 diabetes.5,6
About EMPRISE (NCT03363464, EUPAS20677)1
EMPRISE was initiated in 2016 to complement the EMPA-REG OUTCOME trial results by providing data on the comparative effectiveness, safety, healthcare resource utilisation and costs in routine clinical care compared with DPP-4 inhibitors in people with type 2 diabetes with and without cardiovascular disease.
The study will assess the first five years of empagliflozin use in the U.S. between 2014 to 2019. Over 200,000 people with type 2 diabetes from two commercial U.S. healthcare providers and Medicare are projected to be included by study completion. From 2019, additional EMPRISE studies including Asia and Europe will provide insights from different regions of the world with an international perspective on the use of empagliflozin in routine clinical care.
The EMPRISE study was initiated, and is being led, by academic partners from the Division of Pharmacoepidemiology at Brigham and Women’s Hospital and Harvard Medical School, Boston, USA. The study is part of an academic collaboration between Brigham and Women’s Hospital and Boehringer Ingelheim.
About EMPA-REG OUTCOME® (NCT01131676)2
EMPA-REG OUTCOME® was a long-term, multicenter, randomised, double-blind, placebo-controlled trial of more than 7,000 patients from 42 countries with type 2 diabetes and established cardiovascular disease.
The study assessed the effect of empagliflozin (10 mg or 25 mg once daily) added to standard of care compared with placebo added to standard of care. Standard of care was comprised of glucose-lowering agents and cardiovascular drugs (including for blood pressure and cholesterol). The primary endpoint was defined as time to first occurrence of cardiovascular death, non-fatal heart attack or non-fatal stroke.
The overall safety profile of empagliflozin was consistent with that of previous trials.
About Heart Failure
Heart failure is a progressive, debilitating and potentially fatal condition that occurs when the heart cannot pump enough blood around the body.7 Symptoms of heart failure include difficulty with breathing, swelling – most commonly in feet, legs and ankles – and fatigue, among others.8 Heart failure is a prevalent disease; 26 million people around the world have chronic heart failure.9 There is a high unmet need in the treatment of heart failure, as upto 45 percent of people diagnosed with heart failure will die within one year.10 Additionally, heart failure represents the most common cause of hospitalisation among individuals aged 65 years and over in the United States and Europe.9 Heart failure is highly prevalent in people with diabetes, but approximately half of all people with heart failure do not have diabetes.9,11,12
About Diabetes and Cardiovascular Disease
More than 425 million people worldwide have diabetes, of which over 212 million are estimated to be undiagnosed.13 By 2045, the number of people with diabetes is expected to rise to 629 million people worldwide.13 Type 2 diabetes is the most common form of diabetes, responsible for around 90 percent of diabetes cases in high-income countries.13 Diabetes is a chronic condition that occurs when the body either does not properly produce, or use, the hormone insulin.13
Due to the complications associated with diabetes, such as high blood sugar, high blood pressure and obesity, cardiovascular disease is a major complication and the leading cause of death associated with diabetes.14,15 People with diabetes are two to four times more likely to develop cardiovascular disease than people without diabetes.14,15 In 2017, diabetes caused four million deaths worldwide, with cardiovascular disease as the leading cause.13 Approximately 50 percent of deaths in people with type 2 diabetes worldwide are caused by cardiovascular disease.16,17
Having a history of diabetes at age 60 can shorten a person’s life span by as much as six years compared with someone without diabetes. And having both diabetes and a history of heart attack or stroke by age 60 can shorten a person’s life span by as much as 12 years compared with someone without these conditions.18
More than 50 guidelines have been updated to endorse type 2 diabetes agents with proven cardiovascular benefits since 2016, including a recent Consensus Report initiated by the American Diabetes Association® and European Association for the Study of Diabetes, recommending that, in patients with type 2 diabetes and established atherosclerotic cardiovascular disease, SGLT2 inhibitors (such as empagliflozin) or GLP1 receptor agonists with proven cardiovascular benefits are recommended as part of glycaemic management.19,20
Empagliflozin is an oral, once daily, highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor and the first type 2 diabetes medicine to include cardiovascular death risk reduction data in the label in several countries.21,22,23
Inhibition of SGLT2 with empagliflozin in people with type 2 diabetes and high blood sugar levels leads to excretion of excess sugar in the urine. In addition, initiation of empagliflozin increases excretion of salt from the body and reduces the fluid load of the body’s blood vessel system (i.e. intravascular volume). Empagliflozin induces changes to the sugar, salt and water metabolism in the body that may contribute to the reductions in cardiovascular death observed in the EMPA-REG OUTCOME® trial.
About Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in diabetes that centers on compounds representing several of the largest diabetes treatment classes. The alliance leverages the strengths of two of the world’s leading pharmaceutical companies. By joining forces, the companies demonstrate commitment in the care of people with diabetes and stand together to focus on patient needs. Depending on geographies, the companies either co-promote or separately promote the respective molecules each contributed to the alliance.
1 Patorno E et al. AHA Scientific Sessions 2018; poster Sa1112/1112.
2 Zinman B, Wanner C, Lachin JM, et al. EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-28.
3 EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved). Available at: https://clinicaltrials.gov/ct2/show/NCT03057951?term=emperor&rank=2. Last accessed October 2018.
4 EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced). Available at: https://clinicaltrials.gov/ct2/show/NCT03057977?term=emperor&rank=1. Last accessed October 2018.
5 A phase III randomised, double-blind trial to evaluate the effect of 12 weeks treatment of once daily EMPagliflozin 10 mg compared with placebo on ExeRcise ability and heart failure symptoms, In patients with chronic HeArt FaiLure with preserved Ejection Fraction (HFpEF) (EMPERIAL – preserved). Available at: https://clinicaltrials.gov/ct2/show/NCT03448406?term=EMPERIAL&rank=1. Last accessed October 2018.
6 A phase III randomised, double-blind trial to evaluate the effect of 12 weeks treatment of once daily EMPagliflozin 10 mg compared with placebo on ExeRcise ability and heart failure symptoms, In patients with chronic HeArt FaiLure with reduced Ejection Fraction (HFrEF) (EMPERIAL – reduced). Available at: https://clinicaltrials.gov/ct2/show/NCT03448419?term=EMPERIAL&rank=2. Last accessed October 2018.
7 American Heart Association. What is Heart Failure? Available at: http://www.heart.org/HEARTORG/Conditions/HeartFailure/AboutHeartFailure/What-is-Heart-Failure_UCM_002044_Article.jsp#.WleEeLSFjBI. Last accessed October 2018.
8 Watson RDS, Gibbs CR, Lip GYH. Clinical features and complications. BMJ. 2000;320(7229):236-39.
9 Ambrosy A.P., et al. The Global Health and Economic Burden of Hospitalizations for Heart Failure. J Am Coll Cardiol 2014. 1;63(12):1123-33.
10 Ponikowski P, Anker SG, AlHabib KF, et al. Heart failure: Preventing disease and death worldwide. ESC Heart Fail. 2014;1(1):4-25.
11 Yancy CW., 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. J Am Coll Cardiol. 62(16):e147-e239.
12 Suskin N, et al. Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure. Eur Heart J. 2000;21:1368-75.
13 International Diabetes Foundation. Diabetes Atlas 8th Edition. Available at: http://www.diabetesatlas.org. Accessed: October 2018.
14 World Health Organisation. Diabetes: Fact Sheet no. 312. Available at: www.who.int/mediacentre/factsheets/fs312/en/#. Last accessed October 2018.
15 World Heart Federation. Diabetes as a Risk Factor for Cardiovascular Disease. Available at: www.world-heart-federation.org/cardiovascular-health/cardiovascular-disease-risk-factors/diabetes. Last accessed October 2018.
16 Morrish NJ et al. Mortality and Causes of Death in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia. 2001;44(2):S14–21.9.
17 Einarson TR, Acs A, Ludwig C, et al. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovasc Diabetol. 2018;17:83.
18 The Emerging Risk Factors Collaboration. Association of Cardiometabolic Multimorbidity With Mortality. JAMA. 2015;314(1):52-60.
19 Davies MJ, D’Alessio DA, Fradkin J, et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;dci180033.0033.
20 Data on file. Boehringer Ingelheim Pharmaceuticals, Inc.
21 Jardiance® (empagliflozin) tablets U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Accessed October 2018.
22 European Summary of Product Characteristics Jardiance®, approved May 2018. Data on file.
23 Jardiance® (Full Prescribing Information). Mexico; Boehringer Ingelheim Pharmaceuticals, Inc; 2017.