New data from landmark CVD-REAL study of patients with type-2 diabetes confirms CV benefits associated with SGLT-2 Inhibitors

AstraZenecaAstraZeneca has announced results from a new analysis of its landmark CVD-REAL study, the first large real-world evidence study of its kind evaluating the risk of all-cause death (ACD), hospitalisation for heart failure (hHF), heart attack (myocardial infarction or MI) and stroke in patients with type-2 diabetes (T2D) receiving treatment with SGLT-2 inhibitors (SGLT-2i), including Farxiga (dapagliflozin) versus other glucose-lowering medicines. The results were presented as a late breaker at the American College of Cardiology's 67th Annual Scientific Session and published in the Journal of the American College of Cardiology.(1)

The new analysis (CVD-REAL 2) assessed data from more than 400,000 patients across six countries (Australia, Canada, Israel, Japan, Singapore and South Korea), 74% of whom did not have a history of established cardiovascular (CV) disease. Results showed that across this broad population of patients with T2D, treatment with an SGLT-2i (Farxiga, empagliflozin, ipragliflozin, canagliflozin, tofogliflozin or luseogliflozin) was associated with a 49% lower risk of ACD, 36% of hHF, 19% of MI and 32% of stroke (p≤0.001 for all) compared to other T2D medicines. There was also a 40% lower risk of the composite endpoint of hHF or ACD (p<0.001).(1)

Worldwide, diabetes affects around 425 million adults today, rising to an estimated 629 million (1 in 10 adults) by 2045, with most of these patients residing in Asia Pacific, the Middle East and North America.(2) People with T2D have a two-to-five times greater risk of heart failure (HF) along with an increased risk of a heart attack or stroke.(3) Additionally, in patients with T2D, HF increases their risk of CV death and all-cause mortality by 60-80%.(4,5)

Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases (CVMD), Global Medicines Development, AstraZeneca, said: "The significance and consistency of these latest results from the ongoing CVD-REAL study are encouraging for the clinical community. With the majority of patients in this latest analysis being treated with Farxiga, these results suggest there is a strong association of CV benefits with the use of Farxiga across diverse patient ethnic and racial demographics."

The DECLARE trial (anticipated to read out in the second half of 2018) will answer the important CV efficacy and safety questions about Farxiga. DECLARE is the broadest and most representative CV outcomes trial in the SGLT-2i class, and the only one with the clinically-relevant composite of hHF/CV death as a co-primary endpoint.(6,7,8)

About Farxiga (dapagliflozin)

Farxiga is a first-in-class selective inhibitor of human sodium-glucose co-transporter 2 (SGLT-2) indicated as both monotherapy and as part of combination therapy to improve glycaemic control, with the added benefits of blood pressure reductions and weight loss in adult patients with T2D. Dapagliflozin is indicated as an adjunct to diet and exercise to improve glycaemic control in adults with T2D. Dapagliflozin is not indicated to reduce the risk of CV events, death or hHF.

About CVD-REAL

The CVD-REAL 2 results are consistent with the primary results from CVD-REAL.(1,9) Of the patients in CVD-REAL 2, some 75% were on Farxiga, 9% on empagliflozin, 8% on ipragliflozin (only available in South Korea and Japan), 4% on canagliflozin, 3% on tofogliflozin and 1% on luseogliflozin (both only available in Japan). The CVD-REAL study is ongoing and future analyses will be conducted. The data for the study were obtained from anonymised real-world sources including medical records, claims databases and national registries, and were not independently adjudicated or verified against source documents. The meta-analyses were 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.(1)

About AstraZeneca in Cardiovascular, Renal & Metabolic Diseases (CVMD)

Cardiovascular, renal and metabolic diseases together form one of AstraZeneca's main therapy areas and platforms for future growth. By following the science to understand more clearly the underlying links between the heart, kidney and pancreas, AstraZeneca is investing in a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. Our ambition is to modify or halt the natural course of CVMDs and even regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CVMD health for millions of patients worldwide.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism 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.

1. Kosiborod, M. Lower Risk of Cardiovascular Events and Death Associated with Initiation of SGLT-2 Inhibitors versus Other Glucose Lowering Drugs - Real World Data Across Three Major World Regions with More Than 400,000 Patients: The CVD-REAL 2 Study. Presented at the American College of Cardiology 67th Annual Scientific Session, 2018.
2. International Diabetes Federation. IDF Diabetes Atlas, 8th ed. Brussels, Belgium: International Diabetes Federation; 2017. Available at http://www.diabetesatlas.org/resources/2017-atlas.html. Accessed 21 February 2018.
3. Kannel WB, et al. Role of Diabetes in Congestive Heart Failure: The Framingham Study. American Journal of Cardiology. 1974;34:29.
4. MacDonald MR, et al. Diabetes, left ventricular systolic dysfunction, and chronic heart failure. European Heart Journal. 2008; 29:1224-1240.
5. Cubbon RM, et al. Diabetes mellitus is associated with adverse prognosis in chronic heart failure of ischaemic and non-ischaemic aetiology. Diabetes and Vascular Disease Research. 2013;10(4)330-6.
6. Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events (DECLARE-TIMI58). ClinicalTrials.gov. Available at https://clinicaltrials.gov/ct2/show/NCT01730534. Accessed 10 March 2018.
7. Zinman B. et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. New England Journal of Medicine. 2015;373:2117-28. DOI: 10.1056/NEJMoa1504720.
8. Neal B. et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. New England Journal of Medicine. 2017. DOI: 10.1056/NEJMoa1611925.
9. Kosiborod M, et al. Lower risk of heart failure and death in patients initiated on SGLT-2 inhibitors versus other glucose-lowering drugs: The CVD-REAL Study. Circulation. 2017. doi.org/10.1161/CIRCULATIONAHA.117.029190.

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