AstraZeneca to Present New Cardiovascular Data on FARXIGA in Type 2 Diabetes At ACC 2019
Business Wire 11-Mar-2019 8:00 AM
First sub-analyses from Phase III DECLARE-TIMI 58 trial selected
for late-breaking clinical trial and oral presentations
Data evaluating the cardiovascular (CV) effects of FARXIGA®
(dapagliflozin), including hospitalization for heart failure
(hHF) in adults with type 2 diabetes (T2D) have been selected for
late-breaking clinical trial and oral presentations at the American
College of Cardiology's (ACC) 68th Annual Scientific Session on March
16-18. The data are the first sub-analyses from the Phase III
DECLARE-TIMI 58 trial for FARXIGA.
AstraZeneca will also present the latest results from the BRILINTA® (ticagrelor)
Phase III TREAT trial in patients with the most dangerous form of heart
attack, ST-segment elevation myocardial infarction (STEMI), and a new
heart failure analysis from CVD-REAL, the first large real-world
evidence study of its kind evaluating the risk of all-cause death and
hHF in patients with T2D receiving treatment with a SGLT-2 inhibitor
(SGLT-2i), including FARXIGA.
Joris Silon, Senior Vice President, Cardiovascular, Renal and
Metabolism, BioPharmaceuticals, said: "AstraZeneca is committed to
addressing some of the most pressing health problems faced by patients
with cardiovascular and metabolic diseases, by identifying and
mitigating specific risks. This is particularly important in reducing
the prevalence and burden of heart failure. This disease affects nearly
64 million people globally, and is an early and frequent complication in
patients with type 2 diabetes."
AstraZeneca will present 21 abstracts at ACC 2019. Highlights include
(all times are Central):
FARXIGA Phase III DECLARE-TIMI 58
-
Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2
Diabetes and Prior Myocardial Infarction: A Sub-Analysis From DECLARE
TIMI-58 Trial (Oral Presentation: #906-04. Monday, March 18,
8:12– 8:22 AM, Room 211).
-
Effect of Dapagliflozin on Heart Failure and Mortality in Type 2
Diabetes Mellitus Based on Ejection Fraction (Late-Breaking
Clinical Trial Presentation: #409-14. Monday, March 18,
8:45–8:55 AM, Main Tent, Great Hall).
BRILINTA Phase III TREAT
TREAT was designed to evaluate the safety and efficacy of BRILINTA
compared with clopidogrel in patients who were diagnosed with STEMI
treated with pharmacological thrombolysis.
-
Efficacy of Ticagrelor vs Clopidogrel After Fibrinolytic Therapy in
Patients With ST-Elevation Myocardial Infarction (Late-Breaking
Clinical Trial Presentation: #410-12. Monday, March 18,
11:15–11:25 AM, Main Tent, Great Hall).
Real-world Evidence
New data on the increased and persistent risk of recurrent CV events in
patients with CV disease and additional risk factors, and outcomes of
patients with T2D with reduced or preserved ejection fraction.
-
Novel Approach to Quantifying Risk of Major Cardiovascular Events in
Patients 1-3 Years Post-Myocardial Infarction: Insights From the
Global Prospective TIGRIS Registry (Poster Presentation: #1131-407.
Saturday, March 16, 10:00–10:45 AM, Poster Hall, Hall F).
-
Use of Evidence-Based Preventive Medical Therapies 1-3 Years
Post-Myocardial Infarction in the Prospective Global TIGRIS Registry (Poster
Presentation: #1231-391. Sunday, March 17, 9:45–10:30 AM, Poster
Hall, Hall F).
-
US Burden of Illness in a Commercially-Insured Population and
Assessment of the High Risk and unmEt Need in Patients With CAD and
Type 2 Diabetes (ATHENA): US Burden of Illness in the Diabetes
Collaborative Registry (Poster Presentation: #1129-361 and #1129-362.
Saturday, March 16, 10:00–10:45 AM, Poster Hall, Hall F).
-
Initiation of Sodium Glucose Cotransporter-2 Inhibitors Versus Other
Glucose Lowering Drugs and Risk of Hospitalization For Heart Failure
and Death in Patients With Type 2 Diabetes With Reduced and Preserved
Left Ventricular Ejection Fraction (Moderated Poster Presentation:
#1024-07. Sunday, March 17, 10:15–10:25 AM, Poster Hall, Hall F).
For a complete list of AstraZeneca data presentations at ACC 2019,
please access the ACC website here.
FARXIGA® (dapagliflozin ) is not indicated to reduce the risk
of CV events, heart failure or death.
Indication and Limitations of Use for FARXIGA®
(dapagliflozin) tablets
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.
IMPORTANT SAFETY INFORMATION FOR FARXIGA®
(dapagliflozin) tablets
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 when the eGFR is <45
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
-
Necrotizing Fasciitis of the Perineum (Fournier's Gangrene):
Rare but serious, life-threatening cases have been reported in
patients receiving SGLT2 inhibitors including FARXIGA. Cases have been
reported in females and males. Serious outcomes have included
hospitalization, surgeries, and death. Assess patients presenting with
pain or tenderness, erythema, swelling in the genital or perineal
area, along with fever or malaise. If suspected, institute prompt
treatment and discontinue 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 pre-existing
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
-
Pregnancy: Advise females of potential risk to a fetus
especially during the second and third trimesters.
-
Lactation: FARXIGA is not recommended when breastfeeding.
Please see accompanying US Full
Prescribing Information and Medication
Guide for FARXIGA.
INDICATIONS FOR BRILINTA (ticagrelor) 60 MG AND 90 MG TABLETS
BRILINTA is indicated to reduce the rate of cardiovascular death,
myocardial infarction (MI), and stroke in patients with acute coronary
syndrome (ACS) or a history of myocardial infarction. For at least the
first 12 months following ACS, it is superior to clopidogrel.
BRILINTA also reduces the rate of stent thrombosis in patients who have
been stented for treatment of ACS.
IMPORTANT SAFETY INFORMATION FOR BRILINTA® (ticagrelor)
60-MG AND 90-MG TABLETS
WARNING: (A) BLEEDING RISK, (B) ASPIRIN DOSE AND BRILINTA
EFFECTIVENESS
A. BLEEDING RISK
-
BRILINTA, like other antiplatelet agents, can cause significant,
sometimes fatal bleeding
-
Do not use BRILINTA in patients with active pathological bleeding
or a history of intracranial hemorrhage
-
Do not start BRILINTA in patients undergoing urgent coronary artery
bypass graft surgery
-
If possible, manage bleeding without discontinuing BRILINTA.
Stopping BRILINTA increases the risk of subsequent cardiovascular
events
B. ASPIRIN DOSE AND BRILINTA EFFECTIVENESS
-
Maintenance doses of aspirin above 100 mg reduce the effectiveness
of BRILINTA and should be avoided
CONTRAINDICATIONS
-
BRILINTA is contraindicated in patients with a history of intracranial
hemorrhage or active pathological bleeding such as peptic ulcer or
intracranial hemorrhage. BRILINTA is also contraindicated in patients
with hypersensitivity (eg, angioedema) to ticagrelor or any component
of the product
WARNINGS AND PRECAUTIONS
-
Dyspnea was reported in about 14% of patients treated with BRILINTA,
more frequently than in patients treated with control agents. Dyspnea
resulting from BRILINTA is often self-limiting
-
Discontinuation of BRILINTA will increase the risk of MI, stroke, and
death. When possible, interrupt therapy with BRILINTA for 5 days prior
to surgery that has a major risk of bleeding. If BRILINTA must be
temporarily discontinued, restart as soon as possible
-
Ticagrelor can cause ventricular pauses. Bradyarrhythmias including AV
block have been reported in the post-marketing setting. PLATO and
PEGASUS excluded patients at increased risk of bradyarrhythmias not
protected by a pacemaker, and they may be at increased risk of
developing bradyarrhythmias with ticagrelor
-
Avoid use of BRILINTA in patients with severe hepatic impairment.
Severe hepatic impairment is likely to increase serum concentration of
ticagrelor and there are no studies of BRILINTA in these patients
ADVERSE REACTIONS
-
The most common adverse reactions associated with the use of BRILINTA
included bleeding and dyspnea: In PLATO, for BRILINTA vs clopidogrel,
non-CABG PLATO-defined major bleeding (3.9% vs 3.3%) and dyspnea (14%
vs 8%); in PEGASUS, BRILINTA vs aspirin alone, TIMI Total Major
bleeding (1.7% vs 0.8%) and dyspnea (14% vs 6%)
DRUG INTERACTIONS
-
Avoid use with strong CYP3A inhibitors and strong CYP3A inducers.
BRILINTA is metabolized by CYP3A4/5. Strong inhibitors substantially
increase ticagrelor exposure and so increase the risk of adverse
events. Strong inducers substantially reduce ticagrelor exposure and
so decrease the efficacy of ticagrelor
-
As with other oral P2Y12 inhibitors, co-administration of
opioid agonists delay and reduce the absorption of ticagrelor.
Consider use of a parenteral anti-platelet in ACS patients requiring
co-administration
-
Patients receiving more than 40 mg per day of simvastatin or
lovastatin may be at increased risk of statin-related adverse events
-
Monitor digoxin levels with initiation of, or change in, BRILINTA
therapy
SPECIAL POPULATIONS
-
Lactation: Breastfeeding not recommended
Please read Medication
Guide and Prescribing
Information, including Boxed WARNINGS, for BRILINTA.
NOTES TO EDITORS
About AstraZeneca in Cardiovascular, Renal & Metabolism (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 CVMD diseases and
even regenerate organs and restore function, by continuing to deliver
transformative science that improves treatment practices and
cardiovascular health for millions of patients worldwide.
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
therapy areas - Oncology, Cardiovascular, Renal & Metabolism and
Respiratory. 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.
US-26487 Last Updated 3/19
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