Phase III TREAT trial provides evidence on the use of Brilinta in high-risk patients treated with pharmacological thrombolysis

Brilinta (ticagrelor) has comparable safety to clopidogrel for patients with ST-elevated myocardial infarction (STEMI) treated with fibrinolytic therapy

Secondary analysis of the safety outcomes at 12 months build on
primary analysis at 30 days

18 March 2019

The secondary analysis of the Phase III TREAT trial for Brilinta (ticagrelor) was consistent with the known safety profile of ticagrelor in patients with ST elevation myocardial infarction (STEMI) aged <75 years who received ticagrelor following fibrinolysis compared to clopidogrel after 12 months of treatment. The study was primarily designed to test for non-inferiority of ticagrelor plus aspirin compared to clopidogrel plus aspirin for safety at 30 days and was not statistically powered to detect significance of any treatment effects, but a numerical reduction in cardiovascular events was shown in the ticagrelor arm of the study [ticagrelor: 153 of 1,913 patients (8.0%) vs. clopidogrel 171 of 1,886 patients (9.1%)] at 12 months. This data was presented today as a late-breaking abstract (410-12) at the American College of Cardiology’s 68th Annual Scientific Session in New Orleans.

Elisabeth Björk, Senior Vice President, Head of late Cardiovascular, Renal and Metabolism R&D, Biopharmaceuticals said: “TREAT is closing the knowledge gap, showing that Brilinta can be used in conjunction with thrombolytic therapy. This is particularly important for those patients who are not able to receive surgical intervention in the immediate hours after a heart attack.”

Dr Otavio Berwanger, Chair of the TREAT trial Steering Committee, said: “We are pleased that the secondary analyses of TREAT presented today are comparable with the positive primary results that I presented a year ago, confirming that ticagrelor was non-inferior to clopidogrel with respect to major bleeding in STEMI patients following fibrinolytic therapy. As many people worldwide are pharmacologically managed by fibrinolysis, the study has a significant impact with the potential to support treatment options for these high-risk heart attack patients.”

TREAT investigated the safety and efficacy of ticagrelor 90mg plus aspirin compared to clopidogrel 75mg plus aspirin within 24 hours in patients with STEMI treated with pharmacological thrombolysis, at 30 days and 12 months. TREAT is an investigator-initiated and academically-led trial, financially supported by AstraZeneca.

Secondary efficacy analysis results from TREAT show that STEMI patients aged <75 years who received ticagrelor following fibrinolysis had a similar ischemic risk compared to those receiving clopidogrel, as measured by the secondary efficacy endpoint which was a composite of cardiovascular death, MI or stroke after 12 months of treatment (6.7% vs. 7.3%; HR: 0.93; 95% CI: 0.73-1.18; P = 0.53).1 The combined efficacy endpoint of cardiovascular death, MI, stroke, recurrent ischemia, transient ischemic attack or other arterial thrombotic event occurred in 8.0% of patients treated with ticagrelor and in 9.1% of patients receiving clopidogrel (HR: 0.88; 95% CI: 0.71-1.09; P = 0.25).1 Ticagrelor showed a similar efficacy in preventing cardiovascular events compared to clopidogrel, with a numerical reduction in events in the ticagrelor arm, that was not statistically significant. The study was primarily designed to test for non-inferiority compared to clopidogrel for safety at 30 days and was not statistically powered to detect significance of any treatment effects.

Secondary safety analysis of TREAT was consistent with the known safety profile of ticagrelor. At 12 months, TIMI major bleeding occurred in 1.0% of patients treated with ticagrelor compared to 1.2% of patients receiving clopidogrel (HR: 0.86; 95% CI 0.47-1.56; P = 0.61).1 This is in line with the previously reported primary safety outcome of noninferiority compared to clopidogrel measured as TIMI major bleeding rates at 30 days (P < 0.001 for noninferiority), showing similar safety outcomes between ticagrelor and clopidogrel.2, 3 At 12 months, TIMI minimal bleeding (5.9% vs 2.9%; P<0.01), as well as TIMI bleeding requiring medical attention (3.8% vs 2.1%; P<0.01), were more common with ticagrelor than with clopidogrel.1

Globally, an estimated seven million heart attacks (also known as myocardial infarction or MI) occur every year.4 Although primary percutaneous coronary intervention (PCI) is the preferred treatment strategy,5, 6 many patients don’t have timely access to this procedure, which can only be undertaken in a specialist hospital setting.7 International guidelines recommend pharmacological thrombolysis as an effective alternative treatment in these high-risk patients.5, 6 TREAT was designed to investigate the potential role of ticagrelor in these high-risk patients undergoing pharmacological thrombolysis.



TREAT (Ticagrelor in Patients with ST Elevation Myocardial infarction Treated With Pharmacological Thrombolysis) is a randomised, multicentre, open-label, non-inferiority trial involving almost 3,800 patients, comparing the use of Brilinta (ticagrelor) 180mg (followed by 90mg twice daily for 12 months) plus aspirin versus clopidogrel 300mg (followed by 75mg per day for 12 months) plus aspirin, both administered as early as possible within a maximum of 24 hours following the initial heart attack.8 The trial was primarily designed to assess whether ticagrelor was non-inferior to clopidogrel regarding safety at 30 days. The SmPC states that ticagrelor should be used with caution in patients with concomitant administration of medicinal products that may increase the risk of bleeding (e.g. fibrinolytics) within 24 hours of ticagrelor dosing. The secondary objectives were safety and efficacy outcomes at 12 months which complement the primary analysis. TREAT is an investigator-initiated and academically-led trial, financially supported by AstraZeneca.

About Brilinta (ticagrelor)

Brilinta (ticagrelor) is an oral, reversible, direct-acting P2Y12 receptor antagonist that works by inhibiting platelet activation. Brilinta, together with aspirin, has been shown to significantly reduce the risk of major adverse cardiovascular events (myocardial infarction, stroke or CV death), in patients with acute coronary syndrome (ACS) or a history of MI.

Brilinta, co-administered with aspirin is indicated for the prevention of atherothrombotic events in adult patients with ACS, or for patients with a history of MI and a high risk of developing an atherothrombotic event.

About AstraZeneca in Cardiovascular, Renal & Metabolism (CVRM)

Cardiovascular, renal and metabolic diseases together form one of AstraZeneca’s main therapy areas and a key growth driver for the Company. 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 CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and cardiovascular health for millions of patients worldwide.

About AstraZeneca

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, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit and follow us on Twitter @AstraZeneca.



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1. Berwanger O. Ticagrelor versus Clopidogrel After Thrombolytic Therapy in Patients With ST-Elevation Myocardial Infarction: The TREAT Randomized Trial. JAMA Cardiol 2019 in press.

2. Berwanger O et al. Ticagrelor vs Clopidogrel After Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction: A Randomized Clinical Trial. JAMA Cardiol 2018; 3(5):391–9.

3. Bavry AA. Ticagrelor in Patients With ST-Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis - TREAT; 2018 [cited 30.01.19]. Available from: URL:

4. Roth GA et al. Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. J Am Coll Cardiol 2017; 70(1):1–25.

5. Ibanez B et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018; 39(2):119–77.

6. O'Gara PT et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: Executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013; 127(4):529–55.

7. Rosselló X et al. Global geographical variations in ST-segment elevation myocardial infarction management and post-discharge mortality. Int J Cardiol 2017; 245:27–34.

8. U.S. National Institutes of Health. Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis (TREAT) [Identifier: NCT02298088] [cited 2019 Jan 22]. Available from: URL: