PEGASUS-TIMI 54 Study of AstraZeneca's Brilinta Meets Primary Endpoint

January 14, 2015—AstraZeneca announced that the PEGASUS-TIMI 54 study met its primary efficacy endpoint. The study is a large-scale outcomes trial involving more than 21,000 patients to assess Brilinta (ticagrelor) tablets at either 60-mg twice daily or 90-mg twice daily plus low-dose aspirin for the secondary prevention of atherothrombotic events in patients who had experienced a heart attack 1 to 3 years before the 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.

The company advised that full evaluation of the data is ongoing. 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.

According to AstraZeneca, 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 years and older with a history of heart attack and one additional CV risk factor. The study was designed to better understand the management of patients more than 12 months after MI who remain at high risk for major thrombotic events.

The study is part of AstraZeneca’s PARTHENON program. The PLATO study, involving more than 18,000 acute coronary syndrome (ACS) patients, was the first study in the program and is the basis on which ticagrelor has been approved in more than 100 countries and included in 12 major ACS treatment guidelines globally. Further ongoing PARTHENON studies are investigating ticagrelor for the prevention of cardiovascular events in patients with peripheral arterial disease, ischemic stroke or transient ischemic attack, and in patients with diabetes and coronary atherosclerosis.

AstraZeneca advised that Brilinta is not approved for secondary prevention of atherothrombotic events in patients with a history of MI beyond 1 year or for the prevention of cardiovascular events in patients with PAD, stroke, diabetes, or atherosclerosis.

Brilinta 90-mg dose is indicated to reduce the rate of thrombotic CVS events in patients with ACS (unstable angina, or non–ST-elevation MI, ST-elevation MI). Brilinta has been shown to reduce the rate of a combined endpoint 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.

Brilinta has been studied in ACS in combination with aspirin. Maintenance doses of aspirin > 100 mg decreased the effectiveness of Brilinta and should be avoided, noted AstraZeneca.