PEGASUS-TIMI 54 sub-analysis shows importance of continuing treatment with BRILINTA beyond one year following a heart attack

Monday, 31 August 2015

Data presented at the ESC Congress 2015 reinforce the need for long-term secondary prevention of cardiovascular events

AstraZeneca today announced details of a sub-analysis of the PEGASUS-TIMI 54 study, assessing the effect of BRILINTA® (ticagrelor) in reducing atherothrombotic events in post-heart attack patients, based on the time from withdrawal of their previous P2Y₁₂ inhibitor antiplatelet therapy. Current European guidelines recommend that dual antiplatelet therapy is stopped 12 months after a heart attack. The PEGASUS-TIMI 54 study enrolled patients who had suffered a heart attack one to three years previously.

The data, presented during a Clinical Trial Update hotline session at ESC Congress 2015, demonstrated that withdrawal from P2Y₁₂ inhibitor antiplatelet therapy is associated with heightened risk of ischaemic events, including cardiovascular death, myocardial infarction or stroke.

Patients enrolled into the placebo arm of the PEGASUS-TIMI 54 study who had recently discontinued previous P2Y₁₂ inhibitor antiplatelet therapy (within 30 days) were at heightened risk of developing a subsequent ischaemic event, compared to those who had stopped therapy over 30 days previously, regardless of the time since their original heart attack. This may be due to differences in baseline characteristics (although adjusted for in this analysis) as well as exposing continued risk by the withdrawal of therapy.

Those patients randomised into the ticagrelor arms of the study within 30 days of withdrawal of therapy experienced a 27% reduction in the risk of developing a subsequent event. The benefit of treatment with ticagrelor had the greatest effect in this group, with the effect on risk decreasing as the length of time from last dose increased [≤30 days HR 0.73, >30 days to 360 days HR 0.86, >360 days HR 1.01].

Dr. Marc P. Bonaca, MD, MPH, lead investigator for the sub-analysis study, Associate Physician in Cardiovascular Medicine at Brigham and Women's Hospital and an investigator at the TIMI Study Group, said: “These findings suggest greater benefit in continuing P2Y₁₂ inhibition beyond 12 months therapy without interruption than in re-initiating such therapy in patients who have remained stable for more than 2 years after their MI and more than 1 year off of a P2Y₁₂ inhibitor.”

Marc Ditmarsch, Global Development Lead for BRILINTA said: “We welcome the results of this sub-analysis, which furthers our understanding of the underlying cardiovascular risk for patients who have suffered a heart attack in the past. It also provides further insight into which patients are likely to benefit most from longer term treatment with ticagrelor.”

The PEGASUS-TIMI 54 study investigated the efficacy and safety of ticagrelor at both 60mg and 90mg twice daily, plus low dose aspirin, compared to placebo plus low dose aspirin, for the long-term prevention of atherothrombotic events in patients who had suffered a heart attack one to three years prior to study enrolment. The full results of the PEGASUS-TIMI 54 study were published in the New England Journal of Medicine¹ in March 2015. BRILINTA is currently under review in the EU and the U.S. for use in the chronic secondary prevention of atherothrombotic events in patients who had experienced a heart attack within one to three years.

NOTES FOR EDITORS

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 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 is being conducted in collaboration with the Thrombolysis in Myocardial Infarction (TIMI) Study Group from Brigham and Women’s Hospital (Boston, MA, USA).

The PEGASUS-TIMI 54 study investigated the efficacy and safety of both BRILINTA 60mg and 90mg, twice daily, compared to placebo on a background of low dose aspirin, for the long-term prevention of atherothrombotic events in patients who suffered a heart attack one to three years prior to enrolment. The primary efficacy endpoint is time to first occurrence of any event from the composite endpoint of cardiovascular (CV) death, non-fatal myocardial infarction or non-fatal stroke.

About PARTHENON

The PEGASUS-TIMI 54 study is a key study in the PARTHENON life cycle management program, an AstraZeneca-funded, long-term and evolving global research initiative, designed to address unanswered questions in the management of patients with atherothrombotic disease and to investigate the impact of BRILINTA on reducing atherothrombotic events, including death.

PARTHENON is part of AstraZeneca’s commitment to understanding and advancing treatments for CV diseases to improve patient health.

About BRILINTA

BRILINTA is an oral antiplatelet treatment for acute coronary syndrome (ACS). 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 ACS.

BRILINTA is a registered trademark of the AstraZeneca group.

About the ‘Thrombolysis in Myocardial Infarction’ TIMI Study Group

The TIMI Study Group is affiliated with Brigham and Women’s Hospital and Harvard Medical School and is located in Boston, Massachusetts. It is an Academic Research Organization (ARO) that has conducted numerous practice-changing clinical trials in patients with CV disease or risk factors for CV disease. Amongst its notable achievements, the group developed the TIMI Risk Score, which assesses the risk of death and ischaemic events in patients experiencing unstable angina or a non-ST elevation myocardial infarction.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com

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¹ Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791-800.