WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca today announced results of the first large real-world evidence study of its kind evaluating the risk of hospitalization for heart failure and death from any cause in patients with type-2 diabetes (T2D) receiving treatment with a newer class of diabetes medicines, SGLT-2 inhibitors (SGLT-2i).
The CVD-REAL study assessed data from more than 300,000 patients across six countries, 87% of whom did not have a history of cardiovascular disease. The data showed that across this broad population of patients with T2D compared to other T2D medicines, treatment with SGLT-2i medicines - Farxiga (dapagliflozin), canagliflozin, empagliflozin - reduced the rate of hospitalization for heart failure by 39% (HR 0.61; 95% CI 0.51-0.73; p<0.001) and death from any cause by 51% (HR 0.49; 95% CI 0.41-0.57; p<0.001). For the composite endpoint of hospitalization for heart failure and death from any cause, the reduction was 46% (HR 0.54; 95% CI 0.48-0.60; p<0.001).
Worldwide, diabetes affects around 415 million adults, a number estimated to rise to 642 million by 2040 (1 in 10 adults). People with T2D have a 2-3 times greater risk of heart failure and are at an increased risk of having a heart attack or stroke, and some 50% of deaths in people with T2D are caused by cardiovascular disease.
Bruce Cooper, MD, Vice President and Head of Global Medical Affairs at AstraZeneca, said: “Diabetes is a growing epidemic worldwide, which is associated with significant comorbidities that contribute to an increased risk of costly hospitalizations and even death. Real-world data from this study provide striking evidence that the newer SGLT-2i class of medicines cuts the rate of hospitalizations for heart failure and death by approximately half. CVD-REAL is the first study to observe these effects of SGLT-2i treatment in a much broader and lower risk group of type-2 diabetes patients than previously evaluated in clinical trials.”
The hospitalizations for heart failure analysis was conducted using anonymized patient data from Denmark, Germany, Norway, Sweden, United Kingdom and the United States. Of the data reviewed, 41.8% of patients were on Farxiga (dapagliflozin), 52.7% on canagliflozin and 5.5% on empagliflozin. The analysis of death from any cause was conducted using anonymized patient data from Denmark, Norway, Sweden, United Kingdom and the United States. Of the data reviewed, 51.0% of patients were on Farxiga (dapagliflozin), 42.3% on canagliflozin and 6.7% on empagliflozin.
This is the first of several comparative analyses of CVD-REAL. The study is ongoing and future analyses will be conducted using this dataset as well as data from additional countries. The data for this study were obtained from real-world sources including medical records, claims databases and national registers, and were not independently adjudicated or verified against source documents. The analysis was validated by the independent academic statistical group at St. Luke’s Mid America Heart Institute, Kansas City, US. While CVD-REAL was a large study with a robust propensity-matching technique, given its observational nature the possibility of residual, unmeasured confounding factors cannot be definitively excluded.
Farxiga (dapagliflozin) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type-2 diabetes. Farxiga is not indicated to reduce the risk of CV events, death or hospitalization for heart failure. There have been no clinical trials establishing conclusive evidence of macrovascular risk reduction with Farxiga. The dapagliflozin cardiovascular outcomes trial, DECLARE, is ongoing and expected to provide data in 2019 at the latest.
Important Safety Information for FARXIGA® (dapagliflozin)
- Prior serious hypersensitivity reaction to FARXIGA
- Severe renal impairment (eGFR <30 mL/min/1.73 m2), end-stage renal disease, or patients on dialysis
Warnings and Precautions
- Hypotension: FARXIGA causes intravascular volume contraction, and symptomatic hypotension can occur. Assess and correct volume status before initiating FARXIGA in patients with impaired renal function, elderly patients, or patients on loop diuretics. Monitor for hypotension
- Ketoacidosis has been reported in patients with type 1 and type 2 diabetes receiving FARXIGA. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue FARXIGA, evaluate and treat promptly. Before initiating FARXIGA, consider risk factors for ketoacidosis. Patients on FARXIGA may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis
Acute Kidney Injury and Impairment in Renal Function: FARXIGA
causes intravascular volume contraction and renal impairment, with
reports of acute kidney injury requiring hospitalization and dialysis.
Consider temporarily discontinuing in settings of reduced oral intake
or fluid losses. If acute kidney injury occurs, discontinue and
FARXIGA increases serum creatinine and decreases eGFR. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Before initiating FARXIGA, evaluate renal function and monitor periodically. FARXIGA is not recommended in patients with an eGFR persistently between 30 and <60 mL/min/1.73 m2
- Urosepsis and Pyelonephritis: SGLT2 inhibitors increase the risk for urinary tract infections [UTIs] and serious UTIs have been reported with FARXIGA. Evaluate for signs and symptoms of UTIs and treat promptly
- Hypoglycemia: FARXIGA can increase the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with FARXIGA
- Genital Mycotic Infections: FARXIGA increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately
- Increases in Low-Density Lipoprotein Cholesterol (LDL-C) occur with FARXIGA. Monitor LDL-C and treat per standard of care
- Bladder cancer: An imbalance in bladder cancers was observed in clinical trials. There were too few cases to determine whether the emergence of these events is related to FARXIGA, and insufficient data to determine whether FARXIGA has an effect on preexisting bladder tumors. FARXIGA should not be used in patients with active bladder cancer. Use with caution in patients with a history of bladder cancer
- Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with FARXIGA
In a pool of 12 placebo-controlled studies, the most common adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and placebo respectively were female genital mycotic infections (8.4% vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract infections (5.7% vs 4.3% vs 3.7%).
Use in Specific Populations
- Pregnant Women: There are no adequate and well-controlled studies of FARXIGA in pregnant women. Consider appropriate alternative therapies, especially during the second and third trimesters. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus
- Nursing Mothers: Discontinue FARXIGA or discontinue nursing
Indication and Limitations of Use for FARXIGA® (dapagliflozin)
FARXIGA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. FARXIGA is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Please see accompanying US Full Prescribing Information and Medication Guide for FARXIGA.
NOTES TO EDITORS
About SGLT-2 inhibitors
Dapagliflozin (marketed as Farxiga in the US and Forxiga outside the US) is part of a class of medicines called sodium-glucose cotransporter 2 inhibitors (SGLT-2i) used to manage type-2 diabetes, which remove glucose via the kidneys.
About Dapagliflozin Clinical Trials Program
There are three ongoing outcomes trials for dapagliflozin. DECLARE is a robust randomized, double-blind, multicenter, placebo-controlled cardiovascular outcomes trial enrolling more than 17,000 patients around the world, designed to evaluate the cardiovascular outcomes of dapagliflozin compared with placebo in addition to standard of care, in adults with T2D and high risk of cardiovascular disease (either established cardiovascular disease or multiple cardiovascular risk factors). DECLARE is ongoing and expected to provide data in 2019 at the latest. In addition to DECLARE, AstraZeneca has initiated two outcomes trials, the DAPA-HF and DAPA-CKD trials, to help to define the potential role of dapagliflozin in the management of chronic heart failure and chronic kidney disease respectively, in people with and without type-2 diabetes. Dapagliflozin is not indicated to reduce the risk of cardiovascular events, death, heart failure or the progression of chronic kidney disease.
About AstraZeneca in Cardiovascular and Metabolic Diseases
Cardiovascular, renal and metabolic diseases are key areas of focus for AstraZeneca as part of the company’s strategy for achieving scientific leadership and returning to growth. By collaborating across therapeutic disciplines within the CVMD therapy area, we are addressing the underlying disorders that drive CVMD risk, with the goal of reducing morbidity, mortality and organ damage through innovative therapies. Recognising the growing unmet needs and challenges faced by the millions of people worldwide living with these interrelated diseases, we are determined to understand how they interact and impact one another – and how they can be treated together to save more patients’ lives.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
3334500 Last Updated 3/17