Analysis of PEGASUS-TIMI 54 data reveals persistently high cardiovascular (CV) risk among patients post-heart attack, while the efficacy and safety of ticagrelor remained consistent for the duration of the study
06 September 2017
AstraZeneca announced today the publication of a new analysis from the Brilinta (ticagrelor) Phase III PEGASUS-TIMI 54 trial which reveals that while the risk of ischaemic events in people who have suffered a heart attack (also known as a myocardial infarction, or MI) remains high as late as five years after the event, ticagrelor 60mg continues to provide patients with a consistent and protective effect from major cardiovascular (CV) events.1
The analysis, published in the Journal of the American College of Cardiology, evaluated the number of major adverse cardiac events (MACE) and adverse events in the trial’s 21,162 patients at yearly landmarks (Year-1,Year-2, and Year-3) and found that the CV benefit of ticagrelor 60mg in preventing a repeat major CV event, such as a heart attack, stroke or CV death, was consistent over time. Importantly, the data also showed the greatest benefit in those beginning therapy less than two years after an MI.1
The primary efficacy endpoint of the trial was the composite of CV death, MI, or stroke, with the safety endpoint being major bleeding (also known as Thrombolysis In Myocardial Infarction (TIMI) major bleeding). Additional efficacy endpoints included the individual components of the composite primary endpoint.
In addition, the analysis revealed a 32% (Hazard Ratio (HR) 0.68, 95% CI 0.53 – 0.89) risk reduction in CV death in patients who were less than two years from their last heart attack and treated with ticagrelor 60mg twice daily plus aspirin, vs aspirin alone.1 These new data complement findings from a recent post-hoc sub-analysis of the PEGASUS-TIMI 54 data presented at the annual congress of the ESC (European Society of Cardiology), demonstrating a 29% (HR 0.71, 95% 0.56 – 0.90) risk reduction in CV death for the patient population defined in ticagrelor’s European label.2
Robert Storey, Professor and Honorary Consultant in Cardiology at the University of Sheffield, UK, and member of the Steering Committee of the PEGASUS-TIMI 54 trial, said: “This analysis demonstrates that the efficacy of ticagrelor was maintained over the duration of the trial, providing most benefit in patients who commenced the trial less than two years after a heart attack. These new insights are important, showing that the effectiveness of ticagrelor did not lessen over three years of treatment. This supports the benefit of continuing ticagrelor at a dose of 60mg for patients who tolerate ticagrelor 90mg for the first 12 months after MI.”
This new analysis also highlighted a trend towards lesser excess bleeding with ticagrelor over time, with major bleeding rates remaining consistent with the known safety profile of ticagrelor 60mg and as expected with dual antiplatelet therapy (Year-1 HR 3.22; Year-2 HR 2.07; Year-3 HR 1.65).1 This trend is likely to reflect the selection of patients who have maintained therapy without intolerable bleeding.1
Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases (CVMD), Global Medicines Development, AstraZeneca, said: “This analysis provides support for the long-term efficacy and tolerability of ticagrelor in patients treated within two years of a heart attack and provide reassurance and add clarity on the type of patient likely to benefit from therapy with ticagrelor.”
Publication of these new data follow major updates made in August to clinical practice guidelines from the ESC, including for the first time, the consideration of extended therapy with ticagrelor up to 36 months in high risk medically managed patients.3
NOTES TO EDITORS
About Brilinta / Brilique (ticagrelor)
Ticagrelor is a direct-acting P2Y12 receptor antagonist in a chemical class called cyclo-pentyl-triazolo-pyrimidines (CPTPs).4 It works by inhibiting platelet activation4 and has been shown to reduce the rate of atherothrombotic CV events, such as heart attack or cardiovascular (CV) death, in patients with acute coronary syndromes (ACS).5
Ticagrelor, co-administered with aspirin, also known as acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with ACS, or for patients with a history of myocardial infarction (MI) and a high risk of developing an atherothrombotic event.4
About PEGASUS-TIMI 54 - LANDMARK
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).6
This new sub-analysis studied the rates of major adverse cardiovascular events and TIMI major bleeding at years 1, 2, and 3 of the study.1
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 commercialisation of prescription medicines, primarily for the treatment of diseases in three 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.com and follow us on Twitter @AstraZeneca.
1. Bonaca MP, Storey RF, Theroux P, et al. Efficacy and safety of ticagrelor over time in patients with prior MI in PEGASUS-TIMI 54. J Am Coll Cardiol. 2017:70; 1368-75
2. Dellborg M, et al. Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54. Abstract P3670. ESC Congress 2017. Available at:
Last accessed September 2017.
3. Task Force Members. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. Available at https://academic.oup.com/eurheartj/article/4095043/2017-ESC-focused-update-on-dual-antiplatelet?searchresult=1 Last accessed September 2017.
4. Brilique Summary of Product Characteristics, May 2017. Available at:
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001241/WC500100494.pdf Last accessed September 2017.
5. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045-57.
6. Bonaca MP, Bhatt DL, Braunwald E, et al. Design and rationale for the Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial. Am Heart J. 2014;167:437-44.