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).
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
- 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
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.
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
- 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
- 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%)
- 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
- Lactation: Breastfeeding not recommended
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.
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.
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US-26487 Last Updated 3/19