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AstraZeneca's CVD-REAL Study Shows SGLT-2 Inhibitors Significantly Reduced Hospitalizations for Heart Failure and Death versus Other Type-2 Diabetes Medicines

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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)

Contraindications

  • 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
    promptly treat.
    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

Adverse Reactions

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.

About AstraZeneca

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

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