PEGASUS-TIMI 54 study shows that long-term treatment with BRILINTA reduced thrombotic cardiovascular events in patients with a history of heart attack

Data from 21,000 patient study presented at American College of Cardiology 64th Annual Scientific Session and simultaneously published in New England Journal of Medicine

TORONTO, March 16, 2015 /CNW/ - AstraZeneca this past weekend announced full results from the PEGASUS-TIMI 54 study, a large-scale outcomes trial that investigated BRILINTA® (ticagrelor) tablets plus low dose aspirin, compared to placebo plus low dose aspirin, for the chronic secondary prevention of atherothrombotic events in patients who had experienced a heart attack one to three years prior to study enrolment.

Key findings:

  • Both 90mg and 60mg study doses of ticagrelor with aspirin significantly reduced the primary composite endpoint of cardiovascular (CV) death, myocardial infarction (MI) or stroke compared to placebo.
  • As expected with an oral antiplatelet and consistent with studies in similar patient populations, TIMI Major Bleeding,1 the study's primary safety endpoint, was higher with both doses of ticagrelor plus aspirin compared to placebo plus aspirin. Importantly, the rates of intracranial haemorrhage (bleeding within the skull) and fatal bleeding were low and were similar between study groups and the placebo arm.

The data were presented during the opening late-breaking clinical trial session of the American College of Cardiology's 64th Annual Scientific Session and Expo, and also simultaneously published in the New England Journal of Medicine online.

Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, AstraZeneca, said: "As a company we are committed to furthering cardiovascular research and are proud to have delivered the PEGASUS-TIMI 54 study, AstraZeneca's largest clinical trial, involving more than 21,000 patients worldwide. Building on the landmark PLATO trial in acute coronary syndrome, the positive PEGASUS study adds to the body of evidence for BRILINTA and is the first prospective trial to evaluate longer term dual antiplatelet therapy in higher risk patients with a history of a heart attack.

"We have just submitted regulatory filings to the European Medicines Agency and the US Food and Drug Administration and we look forward to working with these agencies towards a potential new indication in major markets."

Recent research has shown that one in five patients will have a further heart attack, stroke or CV death in the subsequent three years following a heart attack, even if patients were event free after 12 months.2  For patients more than one year on from a heart attack, the current standard of care is aspirin alone. The PEGASUS-TIMI 54 study was designed to investigate the effect of adding ticagrelor at 60mg and 90mg to low dose aspirin on reducing the risk of CV death, heart attack or stroke in patients aged 50 and older with a history of heart attack and one additional CV risk factor.

Efficacy Findings

In this trial, both study doses of ticagrelor significantly reduced the primary endpoint of CV death, MI or stroke compared to placebo. The rates at 3 years were 7.85% in the ticagrelor 90mg arm, 7.77% in the ticagrelor 60mg arm, and 9.04% in the placebo arm (Hazard Ratio (HR) for ticagrelor 90mg vs placebo 0.85, 95% CI 0.75 – 0.96, P=0.0080; HR for ticagrelor 60mg vs placebo 0.84, 95% CI 0.74 – 0.95, P=0.0043).

The effect of ticagrelor on each of the components of the primary endpoint was consistent. A numerical decrease in the secondary endpoints of cardiovascular death and all cause mortality was observed, but did not reach statistical significance.

In addition, the primary efficacy endpoint of both doses of ticagrelor appeared consistent across major subgroups including age, sex, index MI type (STEMI/NSTEMI), time from qualifying MI, diabetes, aspirin dose, history of percutaneous intervention (angioplasty), and geographical region.

Safety Findings

As expected, TIMI Major bleeding was higher with both doses of ticagrelor compared to placebo, with rates at 3 years of 2.60% in the ticagrelor 90mg arm, 2.30% in the ticagrelor 60mg arm, and 1.06% in the placebo arm (HR for ticagrelor 90mg vs placebo 2.69, 95% CI 1.96 – 3.70, p<0.001; HR for ticagrelor 60mg vs placebo 2.32, 95% CI 1.68 – 3.21, p<0.001).

However, the rates of fatal bleeding or intracranial haemorrhage were low and similar between treatment arms.

Fatal bleeding rates at 3 years were 0.11% in the ticagrelor 90mg arm, 0.25% in the ticagrelor 60mg arm, and 0.26% in the placebo arm (HR for ticagrelor 90mg vs placebo 0.58, 95% CI 0.22 – 1.54, p=0.27; HR for ticagrelor 60mg vs placebo 1.00, 95% CI 0.44 – 2.27, p=1.00).

Intracranial haemorrhage rates at 3 years were 0.56% in the ticagrelor 90mg arm, 0.61% in the ticagrelor 60mg arm, and 0.47% in the placebo arm (HR for ticagrelor 90mg vs placebo 1.44, 95% CI 0.83 – 2.49, p=0.19; HR for ticagrelor 60mg vs placebo 1.33, 95% CI 0.77 – 2.31, p=0.31).

The PEGASUS-TIMI 54 study, AstraZeneca's largest outcomes trials involving more than 21,000 patients from over 1,100 sites in 31 countries, is part of the 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.

BRILINTA is not approved for secondary prevention of atherothrombotic events in patients with a history of heart attack beyond one year or for the prevention of cardiovascular events in patients with peripheral arterial disease, stroke, diabetes or atherosclerosis.

NOTES TO EDITORS

  1. TIMI Major Bleeding Classification:
    • Any intracranial bleeding, or
    • Clinically overt signs of haemorrhage associated with a drop in hemoglobin (Hgb) of ≥5 g/dL (or, when hemoglobin is not available, a fall in hematocrit of ≥15%), or
    • Fatal bleeding (a bleeding event that directly led to death within 7 days).
  2. Rapsomaniki E, Thuresson M, Yang E, et al. International comparison of outcomes among 140,880 patients stable after acute MI; real world evidence from electronic health and administrative records. Presented at European Society of Cardiology Congress, Barcelona, Spain; 30 August – 3 September 2014.

Heart Attacks in Canada
More than 84,000 Canadians suffer a heart attack each year,1 and one in five patients will suffer a second heart attack, within three years of the first event.2 An estimated 1.6 million people in Canada are living with the effects of cardiovascular disease3 and nine in 10 Canadians have at least one risk factor for heart disease or stroke.4

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, including 56 in Canada, 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). Canadian participation in the study was high with 1,307 patients selected for randomization, translating to the fourth largest overall recruitment globally within the 31 participating countries. 

About BRILINTA®
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).

In Canada, BRILINTA, co-administered with aspirin, is indicated for the secondary prevention of atherothrombotic events in a broad ACS population. Specifically, BRILINTA is indicated for use in patients who are diagnosed with unstable angina (UA) or who experience a heart attack [either non-ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI)]. BRILINTA is indicated for use in these patients whether they are to be managed with medical therapy alone or via an invasive procedure [percutaneous coronary intervention (PCI) and/or coronary artery by-pass graft (CABG)]. BRILINTA is recommended to be co-administered with a low maintenance dose of aspirin (75-150 mg).

BRILINTA is a trademark of the AstraZeneca group of companies.

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 one of the oldest cardiovascular academic research organisation in the United States and has conducted numerous practice-changing clinical trials in patients with CV disease or risk factors for CV disease.

About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology, and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. AstraZeneca's Canadian headquarters are located in Mississauga, Ontario. For more information, please visit the company's website at www.astrazeneca.ca.

_______________________________
1 Charles River Associates' Life Sciences Practice. The burden of acute coronary syndrome:The second leading cause of death in Canada. Available http://www.charlesriverassociates.com/sites/default/files/publications/Burden-of-acute-coronary-syndrome-in-Canada.pdf Accessed  March 2, 2015
2 Rapsomaniki E, Thuresson M, Yang E, et al. International comparison of outcomes among 140,880 patients stable after acute MI; real world evidence from electronic health and administrative records. Presented at European Society of Cardiology Congress, Barcelona, Spain; 30 August – 3 September 2014.
3 The Heart and Stroke Foundation. Getting to the Heart of the Matter.  February 2015. Available http://www.heartandstroke.com/atf/cf/%7B99452d8b-e7f1-4bd6-a57d-b136ce6c95bf%7D/HSF-2015-HEART-MONTH-REPORT-V2.PDF. Accessed February 23, 2015.
4 "Heart Disease – Heart Health" The Government of Canada, 2015. Accessed February 5, 2015. http://healthycanadians.gc.ca/diseases-conditions-maladies-affections/disease-maladie/heart-disease-eng.php

SOURCE AstraZeneca Canada Inc.

Image with caption: "~1 in 5 post-MI patients who were event-free for the first year after a heart attack, went on to suffer a heart attack, stroke or cardiovascular death in the subsequent 3 years. (CNW Group/AstraZeneca Canada Inc.)". Image available at: http://photos.newswire.ca/images/download/20150316_C6262_PHOTO_EN_13262.jpg

For further information: Media Enquiries: Courtney McNamara, Edelman, Tel: (416) 849-3149, Courtney.McNamara@edelman.com; Daniela Cohen, AstraZeneca Canada, Tel: (905) 615-6827, daniela.cohen@astrazeneca.com


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