AstraZeneca announced that the PEGASUS-TIMI 54 study, a large scale outcomes trial involving over 21,000 patients, successfully met its primary efficacy endpoint. The study assessed Brilinta (ticagrelor) tablets at either 60mg twice daily or 90mg twice daily plus low-dose aspirin for the secondary prevention of atherothrombotic events in patients who had experienced a heart attack one to three years prior to study start. The primary efficacy endpoint was a composite of cardiovascular (CV) death, myocardial infarction (MI) or stroke.

Preliminary analysis did not reveal any unexpected safety issues. Full evaluation of the data is ongoing.

Elisabeth Björk, vice president, head of cardiovascular and metabolic diseases, Global Medicines Development, AstraZeneca, said: “We are very pleased with the top line results of the PEGASUS-TIMI 54 study, the second positive major outcomes study in the PARTHENON programme. The results build on existing understanding of the benefits of Brilinta for patients with acute coronary syndrome and offer important clinical insights into its potential role for the longer term prevention of cardiovascular events. We look forward to presenting the data later this year.”

The PEGASUS-TIMI 54 study investigated two different doses of ticagrelor on a background of low dose aspirin versus placebo plus low dose aspirin, in patients aged 50 and older with a history of heart attack and one additional CV risk factor1. The study was designed to better understand the management of patients more than 12 months after their heart attack, who remain at high risk for major thrombotic events.

Complete results from the PEGASUS-TIMI 54 study will be submitted to a scientific meeting in 2015 and pending further analysis, AstraZeneca plans to file this data with regulatory health authorities. Ticagrelor is not approved for secondary prevention of atherothrombotic events in patients with a history of heart attack beyond one year.

The PEGASUS-TIMI 54 study is part of AstraZeneca’s PARTHENON programme. The PLATO study, involving over 18,000 patients, was the first study in the programme and is the basis on which ticagrelor has been approved in over 100 countries and included in 12 major ACS treatment guidelines globally. Further ongoing PARTHENON studies are assessing ticagrelor for the prevention of cardiovascular events in patients with peripheral arterial disease, ischaemic stroke or transient ischaemic attack, and in patients with diabetes and coronary atherosclerosis.

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 ever outcomes trials with more than 21,000 patients from over 1,100 sites in 31 countries in Europe, the Americas, Africa and Australia/Asia. It was conducted in collaboration with the Thrombolysis in Myocardial Infarction (TIMI) Study Group from Brigham and Women’s Hospital (Boston, MA, USA).

The PEGASUS study is part of PARTHENON, the largest ever AstraZeneca cardiovascular outcomes programme, involving nearly 80,000 patients at high risk of cardiovascular events (MI, stroke and/or cardiovascular death) due to their underlying disease. PARTHENON aims to enhance scientific understanding of the role of ticagrelor in the treatment of atherothrombotic conditions. It includes five key studies covering broad patient populations across varying timescales. The studies encompass a wide range of cardiovascular disorders, including stroke/transient ischaemic attack (SOCRATES), peripheral arterial disease (EUCLID) and patients with type 2 diabetes at high risk of cardiovascular events (THEMIS).

The PARTHENON programme aims to support four new indications for ticagrelor over the next 4 years.

Brilinta is a direct-acting P2Y12 receptor antagonist in a chemical class called cyclo-pentyl-triazolo-pyrimidines (CPTPs). Brilinta works by inhibiting platelet activation and has been shown to reduce the rate of thrombotic CV events, such as a heart attack or CV death, in patients with acute coronary syndrome (ACS).

Brilinta (90mg) is indicated to reduce the rate of thrombotic CV events in patients with ACS (unstable angina [UA], non–ST-elevation myocardial infarction [NSTEMI], or ST-elevation myocardial infarction [STEMI]). Brilinta has been shown to reduce the rate of a combined end point of CV death, MI, or stroke compared to clopidogrel. The difference between treatments was driven by CV death and MI with no difference in stroke. In patients treated with percutaneous coronary intervention, it also reduces the rate of stent thrombosis.