AstraZeneca and MedImmune, its global biologics research and development arm, will be underlining its scientific focus on cardiovascular, renal and metabolic diseases (CVMD) with 28 presentations, including two late-breaking trials, at the American Heart Association (AHA) Scientific Sessions, November 11-15, 2017 in Anaheim, California.
Ludovic Helfgott, Vice President, Cardiovascular and Metabolic Diseases, said: “With the breadth of our scientific updates at AHA 2017, we are at the forefront of the clinical debate, exploring the often unseen but vital connections between cardiovascular, renal and metabolic diseases. This approach embodies our commitment to improving outcomes for patients while reducing long-term morbidity and mortality.”
Key among the data being presented are two late-breaking presentations selected by the AHA: the China-based DACAB study (Efficacy of Different Antiplatelet Therapy Strategy after Coronary Artery Bypass Grafting); and the EXSCEL (EXenatide Study of Cardiovascular Event Lowering) trial, plus data for potential new CVMD medicines.
- The DACAB study compares the use of ticagrelor plus aspirin versus aspirin alone, and ticagrelor alone following elective coronary artery bypass graft surgery (CABG), to assess patency of the grafts. Ticagrelor is not approved in elective CABG and cannot be used as monotherapy. (Session LBS.01).
- A new analysis of the EXSCEL clinical trial, the largest and most inclusive CV outcomes trial of any glucagon-like peptide-1 receptor agonist (GLP-1 RA), with more than 14,500 patients at 687 trial sites across 35 countries, aims to further demonstrate the effect of exenatide once-weekly on CV morbidity and mortality in patients with type-2 diabetes. This new analysis adds to results presented at the recent annual meeting of the European Association for the Study of Diabetes (EASD), and published simultaneously in the New England Journal of Medicine. Exenatide is not indicated to reduce the risk of CV outcomes. (Session LBS.04).
- Presentations at AHA also include early stage data for potential new medicines, as monotherapy and in combinations, in areas including cardiac regeneration, chronic kidney disease, acute coronary syndromes, and chronic heart failure. These include phase IIa data of MEDI6012, a recombinant human lecithin-cholesterol acyltransferase (LCAT) being evaluated for the treatment of coronary artery disease (Session LB.APS.06 – S2107) and chronic heart failure (CHF), as well as data from AZD5718 our 5-lipoxygenase activating protein (FLAP), a potential treatment for ACS (Session IN.APS.02 – S4093).
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
- 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
BRILINTA (ticagrelor) tablets 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.
In the management of ACS, initiate BRILINTA treatment with a 180-mg loading dose. Administer 90 mg twice daily during the first year after an ACS event. After one year administer 60 mg twice daily. Use BRILINTA with a daily maintenance dose of aspirin of 75-100 mg.
IMPORTANT SAFETY INFORMATION FOR BYDUREON (exenatide extended-release) for injectable suspension, 2 mg
WARNING: RISK OF THYROID C-CELL TUMORS
- Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether BYDUREON causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of exenatide extended-release-induced rodent thyroid C-cell tumors has not been determined
- BYDUREON is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with the use of BYDUREON and inform them of symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for detection of MTC in patients treated with BYDUREON
- Personal or family history of MTC, patients with MEN 2
- Prior serious hypersensitivity reactions to exenatide or product components
WARNINGS AND PRECAUTIONS
- Acute Pancreatitis including fatal and non-fatal hemorrhagic or necrotizing pancreatitis has been reported. After initiation, observe patients carefully for symptoms of pancreatitis. If suspected, discontinue promptly and do not restart if confirmed. Consider other antidiabetic therapies in patients with a history of pancreatitis
- Hypoglycemia Risk of hypoglycemia is increased when exenatide is coadministered with insulin or insulin secretagogues. Consider lowering the dose of these agents when coadministered with BYDUREON
- Acute Kidney Injury and Impairment of Renal Function Altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis and kidney transplantation have been reported. Not recommended in patients with severe renal impairment or end-stage renal disease. Use caution in patients with renal transplantation or moderate renal impairment
- Gastrointestinal Disease Because exenatide is commonly associated with gastrointestinal adverse reactions, not recommended in patients with severe gastrointestinal disease (eg, gastroparesis)
- Immunogenicity Patients may develop antibodies to exenatide. Patients with higher titer antibodies may have an attenuated HbA1c response. In clinical trials, attenuated glycemic response was associated with BYDUREON-treated patients. If worsening of or failure to achieve adequate glycemic control occurs, consider alternative antidiabetic therapy
- Hypersensitivity Reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema). If this occurs, patients should discontinue BYDUREON and promptly seek medical advice
- Injection-Site Reactions Serious reactions (eg, abscess, cellulitis, and necrosis), with or without subcutaneous nodules, have been reported
- Macrovascular Outcomes No clinical studies establishing conclusive evidence of macrovascular risk reduction with exenatide
Most common (≥5%) and occurring more frequently than comparator in clinical trials: nausea (16.9%), diarrhea (12.7%), headache (8.0%), vomiting (6.8%), constipation (5.9%), injection-site pruritus (5.9%), injection-site nodule (5.3%), and dyspepsia (5.1%).
- Oral Medications BYDUREON slows gastric emptying and may reduce the rate of absorption of orally administered drugs
- Warfarin Increased international normalized ratio (INR) sometimes associated with bleeding has been reported with concomitant use of exenatide with warfarin. Monitor INR frequently until stable upon initiation of BYDUREON
Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
INDICATION AND LIMITATIONS OF USE
BYDUREON is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
- Not recommended as first-line therapy for patients inadequately controlled on diet and exercise
- Not a substitute for insulin. Should not be used to treat type 1 diabetes mellitus or diabetic ketoacidosis
- Not recommended for use with insulin
- Do not coadminister with other exenatide-containing products
- Not studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis
NOTES TO EDITORS
For the full listing of AstraZeneca/MedImmune Presentations at AHA 2017, please visit http://www.abstractsonline.com/pp8/#!/4412/
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.
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.
Michele Meixell +1 302 885 2677
Alexandra Engel +1 302 885 2677
US-15833 Last Updated 11/17