Thursday, 31 March 2016
First major US guideline to include expanded indication for BRILINTA in patients with a heart attack beyond one year
AstraZeneca today confirmed that the American College of Cardiology (ACC) and American Heart Association (AHA) have released a treatment guideline on the duration of dual antiplatelet therapy (DAPT). BRILINTA (ticagrelor) is now preferred over clopidogrel for the management of patients with acute coronary syndrome (ACS) who have received a coronary stent and in non-ST Elevation acute coronary syndrome (NSTE-ACS) patients treated with medical therapy alone (Class IIa LOE: B-R). This update is the first time the ACC/AHA has recommended BRILINTA over clopidogrel for patients who have experienced a ST-elevation myocardial infarction (STEMI).
The update is also the first US guideline to provide the medical community with insights drawn from the PEGASUS-TIMI 54 trial. The guideline supports continuation of P2Y12 therapy beyond 12 months in prior MI patients who are not at high bleeding risk (Class IIb LOE: A). Full details of the updated guideline are available on the ACC website.
Elisabeth Bjork, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, AstraZeneca said: “We are pleased that the ACC/AHA have further recognized the role of BRILINTA across a broad spectrum of ACS. This update reflects the clinical confidence of BRILINTA as a treatment option for heart attack patients in the acute setting and in the longer-term.”
The US Food and Drug Administration approved BRILINTA at a 60mg dose for patients with a history of heart attack in September 2015. BRILINTA is the only P2Y12 inhibitor that has been approved by the FDA in the past 10 years, for long-term use in patients with a history of MI. In the US, BRILINTA is indicated to reduce the rate of CV death, MI, and stroke in patients with ACS or a history of MI. For at least the first 12 months following ACS, it has been proven superior to clopidogrel. BRILINTA also reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS.
This update comes ahead of American College of Cardiology's 65th Annual Scientific Sessions. Data will be presented on two new sub-analyses from the PEGASUS trial. The sub-analyses include prior MI patients with either peripheral artery disease (PAD) or diabetes. The data will be presented on April 3 and 4 respectively.
In the second half of 2016, data are expected from the ongoing EUCLID trial in PAD, which is the fourth trial to read-out from the PARTHENON program, assessing the potential of BRILINTA in additional high-risk patient populations.
BRILINTA is not approved for the prevention of cardiovascular events in patients with PAD, stroke or diabetes who have not experienced a prior MI.
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
- 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
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.
Patients can find out more information about BRILINTA at www.BRILINTA.com or by calling 1-888-412-7454.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visitwww.fda.gov/safety/medwatch or call 1-800-FDA-1088.
About the 2016 ACC/AHA Guideline Focused Update
The ACC/AHA Focused Update on the Duration of Dual Antiplatelet Therapy (DAPT) impacts six already released ACC/AHA Clinical Practice Guidelines.
Within the updated guideline, it is recommended that in patients with ACS (STEMI or NSTE-ACS) treated with DAPT after coronary stent implantation and in patients with NSTE-ACS treated with medical therapy alone (without revascularization), it is reasonable to use ticagrelor in preference to clopidogrel for maintenance P2Y12 inhibitor therapy Class IIa (LOE: B-R).
Regarding longer-term use of DAPT beyond 12 months, the guidelines recommend that in patients with an MI that occurred 1 to 3 years earlier who have tolerated DAPT without a bleeding complication and who are not at high bleeding risk (e.g., prior bleeding on DAPT, coagulopathy, oral anticoagulant use), further continuation of DAPT may be reasonable Class IIb (LOE: A).
Regarding use of DAPT for the first 12 months after an ACS event the guidelines recommend that patients with ACS treated with DAPT after BMS or DES implantation, P2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor) should be given for at least 12 months Class I (LOE: B-R). Patients with ACS who are managed with medical therapy alone (without revascularization or fibrinolytic therapy) and treated with DAPT, P2Y12 inhibitor therapy (either clopidogrel or ticagrelor) should be continued for at least 12 months Class I (LOE: B-R). As well as in patients with ACS being treated with DAPT who undergo CABG, P2Y12 inhibitor therapy should be resumed after CABG to complete 12 months of DAPT therapy after ACS Class I (LOE: C-LD).
- Class I recommends that that procedure/treatment should be performed/administered
- Class IIa states that it is reasonable to perform procedure/administer treatment
- Class IIb states that procedure/treatment may be considered
- Level A: High quality evidence from more than 1 RCT, meta-analysis of high quality RCTs, or one or more RCTs collaborated by high-quality registry studies
- Level B-R: Moderate quality evidence from 1 or more RCTs or meta-analyses of moderate-quality RCTs
- Level C-LD: Randomized or nonrandomized observational or registry studies with limitations of design or execution, meta-analysis of such studies, or physiological or mechanistic studies in human subjects.
To access the full ACC/AHA guideline, visit http://content.onlinejacc.org/article.aspx?articleID=2507082.
About PEGASUS-TIMI 54
PEGASUS-TIMI 54 (PrEvention with TicaGrelor of SecondAry Thrombotic Events in High-RiSk Patients with Prior AcUte Coronary Syndrome – Thrombolysis In Myocardial Infarction Study Group) is one of AstraZeneca’s largest outcomes trial with more than 21,000 patients from over 1,100 sites in 31 countries. The study assessed BRILINTA® (ticagrelor) tablets at either 60 mg twice daily or 90 mg twice daily plus once daily low-dose aspirin compared to placebo plus once daily low-dose aspirin for the secondary prevention of atherothrombotic events in patients ≥ 50 years of age who had experienced a heart attack one to three years prior to study start and had at least 1 risk factor for thrombotic cardiovascular events ( age ≥ 65 years, Diabetes mellitus requiring medication, at least one other prior MI, evidence of multivessel coronary artery disease or a creatinine clearance < 60 ml/min). The primary efficacy endpoint was a composite of cardiovascular (CV) death, myocardial infarction (MI) or stroke at 36 months. Patients were treated for at least 12 months and up to 48 months with a median follow-up time of 33 months. BRILINTA 60 mg plus aspirin significantly reduced the primary composite end point of CV death, MI, or stroke by 16% RRR (ARR 1.27%) vs placebo plus aspirin at 3 years (7.8% vs 9.0% [HR: 0.84, 95% CI: 0.74–0.95]; P=0.0043). In PEGASUS, TIMI Major Bleeding rates were 1.7% for BRILINTA 60 mg plus aspirin vs 0.8% for placebo plus aspirin. TIMI Major or Minor Bleeding rates were 2.4% for BRILINTA 60 mg plus aspirin vs 1.0% for placebo plus aspirin. Only the 60 mg dose is approved for use in patients with a history of MI beyond 12 months. The study was conducted in collaboration with the Thrombolysis in Myocardial Infarction (TIMI) Study Group from Brigham and Women’s Hospital (Boston, MA, USA).
About the PARTHENON Program
PEGASUS-TIMI 54 is part of PARTHENON, the largest ever AstraZeneca CV outcomes program, involving nearly 80,000 patients at high risk of CV events (MI, stroke and/or CV death) due to their underlying disease. Through the PARTHENON program, AstraZeneca aims to address unmet patient needs by enhancing scientific understanding of the potential role of BRILINTA in the treatment of atherothrombotic conditions. It includes five key studies covering broad patient populations across varying timescales, including the completed PEGASUS-TIMI 54, PLATO and SOCRATES trials, and the ongoing EUCLID [peripheral arterial disease (PAD)] and THEMIS (type 2 diabetes at high risk for CV events) trials.
BRILINTA is an oral antiplatelet treatment for ACS or prior-MI. BRILINTA is a direct-acting P2Y12receptor antagonist in a chemical class called cyclo-pentyl-triazolo-pyrimidines (CPTPs) and works by inhibiting platelet activation.
BRILINTA is indicated to reduce the rate of CV death, MI and stroke in patients with acute coronary syndrome (ACS) or a history of MI. 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.
BRILINTA is available in 90-mg and 60-mg tablets and, in the management of ACS, treatment is initiated with a 180-mg loading dose. During the first year after an ACS event, 90 mg is administered twice daily. After one year, 60 mg is administered twice daily. BRILINTA should be used with a daily maintenance dose of aspirin of 75-100 mg.
BRILINTA is a registered trademark of the AstraZeneca group.
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas - respiratory, inflammation, autoimmune disease (RIA), cardiovascular and metabolic disease (CVMD) and oncology – as well as in infection and neuroscience. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visitwww.astrazeneca-us.com.
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3163210 Last Updated 3/16