Monday, 1 September 2014
Results are in line with new ESC/EACTS 2014 Guidelines on Myocardial Revascularisation which give a class I recommendation to start dual antiplatelet therapy in STEMI patients at first medical contact
AstraZeneca today announced the results of the Phase IV ATLANTIC study, which indicates that the profile of BRILINTA/BRILIQUE™ (ticagrelor) is comparable whether administered in a pre-hospital or in-hospital setting to ST segment elevation myocardial infarction (STEMI) patients. The data will be presented during the European Society of Cardiology congress1 taking place between 30 August and 3 September 2014 in Barcelona.
Results of the ATLANTIC study were also published today in the New England Journal of Medicine.
ATLANTIC was designed to evaluate pre-hospital administration versus in-hospital administration of ticagrelor in terms of pre-percutaneous coronary intervention (PCI) - or angioplasty - procedural effectiveness, bleeding at 24 hours and 30 days and the pre-specified composite endpoint of death, MI, stroke, urgent revascularisation and definite acute stent thrombosis at 30 days. Research shows that the effectiveness of PCI may be impacted by delays caused when transferring patients with acute STEMI to the catheterisation lab in hospital, and that STEMI patients have a high risk of persistent and total coronary occlusion (obstruction of blood flow in the coronary artery), resulting in a higher risk of short-term mortality2.
There was no statistically significant difference between the pre-hospital or in-hospital study arms in the co-primary endpoints of pre-PCI procedural effectiveness; percentage of patients not achieving ST segment elevation resolution ≥70% before PCI (OR 0.93;95% CI 0.69, 1.25; p=0.632), and percentage of patients not reaching thrombolysis in myocardial infarction (TIMI) flow grade 3 in the infarct-related - or “culprit” - artery at initial angiography (OR 0.97; 95% CI 0.75, 1.25; p=0.821).
The ATLANTIC study was not powered to look at clinical outcomes, however there was no difference between the two arms in terms of composite endpoint. The pre-hospital administration of ticagrelor indicates a risk reduction of post-PCI stent thrombosis (a secondary endpoint) both at 24 hours (0% versus 0.8%; nominal p = 0.0078) and 30 days (0.2% versus 1.2%; nominal p=0.023).
The study results also showed that there was no difference in bleeding events between the pre-hospital and in-hospital study arms, the primary safety endpoint of the study. Rates of bleeding events that were not related to coronary-artery bypass grafting were low during the first 48 hours after the initial dose, and from 48 hours through to 30 days, and the rates did not differ significantly between the two study groups, indicating that earlier, pre-hospital administration of ticagrelor in patients with acute STEMI can be undertaken without increased bleeding risk3.
“ATLANTIC has indicated that in STEMI patients undergoing primary PCI, ticagrelor has the flexibility to be used safely in either pre-hospital or in-hospital settings with a potential benefit on the early occurrence of stent thrombosis” said Dr. Gilles Montalescot, MD, Professor of Cardiology at Pitié-Salpétrière Hospital, Paris, France, and Primary Investigator of the ATLANTIC study. “These results are in line with the new ESC/EACTS 2014 Guidelines on Myocardial Revascularisation that were also presented at this year’s ESC conference, which give a class I recommendation to start dual antiplatelet therapy in STEMI patients at first medical contact.”
Marc Ditmarsch, Global Development Lead for BRILINTA said: “The results from the ATLANTIC study allow us to better understand the role of BRILINTA in treating STEMI patients. The data indicates that BRILINTA has the flexibility to be initiated pre-hospital or in-hospital in STEMI patients with no adverse impact on bleeding. While not the primary focus of this study, the data indicating a risk reduction of post-PCI stent thrombosis in those patients who received BRILINTA before reaching hospital are also encouraging, and warrant further investigation.”
ATLANTIC is a key trial building on the results of the pivotal PLATO study, which demonstrated that treatment with ticagrelor plus aspirin for 12 months was associated with a 21% relative risk reduction (RRR) in cardiovascular death (4% vs. 5.1%; 1.1% ARR; P=0.001) and a 16% RRR in MI compared to clopidogrel plus aspirin at 12 months (5.8% vs. 6.9%; 1.1% ARR; P<0.005). PLATO was the first study to report in the global PARTHENON programme, designed to address unanswered questions in atherothrombotic disease and to investigate the impact of BRILINTA on reducing atherothrombotic events. PARTHENON is AstraZeneca’s largest ever clinical trial programme, involving more than 80,000 patients worldwide, and is part of the company’s commitment to understanding and advancing treatments for cardiovascular diseases to improve patient health.
NOTES FOR EDITORS
ATLANTIC (A 30 Day Study to Evaluate Efficacy and Safety of Pre-hospital vs. In-hospital Initiation of Ticagrelor Therapy in STEMI Patients Planned for Percutaneous Coronary Intervention) was an international, multicentre, randomised, double blind Phase IV study that aimed to determine optimal timing for initiation of antiplatelet therapy by evaluating whether ticagrelor administered pre-hospital, preferably in the ambulance setting during transfer, could improve coronary reperfusion in STEMI patients intended for primary PCI.
Patients (n=1862) were randomised to receive either a loading dose of BRILINTA 180 mg for the pre-hospital administration (n=909) and placebo for in-hospital administration, or a placebo for pre-hospital administration and BRILINTA 180 mg loading dose for in-hospital administration (n=953). The median time difference between pre-hospital and in-hospital administration of BRILINTA loading dose was 31 minutes. After discharge, all patients continued on BRILINTA 90 mg twice daily for 30 days, with a recommendation that treatment be continued for 12 months.
- The co-primary endpoints were the percentage of patients (i) not achieving ≥70% (complete) ST-segment elevation resolution pre-PCI, or (ii) not reaching TIMI flow grade 3 in the infarct-related artery at pre-PCI angiography.
- Pre-specified secondary endpoints included the composite of death, MI, stent thrombosis, stroke, urgent revascularisation at 30 days; definite stent thrombosis alone at 30 days; thrombotic bail-out with GP IIb/IIIa inhibitors; TIMI flow grade 3 at the end of the procedure; and complete ST-segment elevation resolution at 60 minutes post-PCI.
- Safety endpoints included major, life-threatening or minor bleeding (excluding coronary artery bypass graft-related [CABG] bleeding) within the first 48 hours and over the 30 day treatment period, evaluated using the PLATO, TIMI, STEEPLE, ISTH, GUSTO and BARC bleeding definitions.
Ticagrelor is an oral antiplatelet treatment for acute coronary syndromes (ACS). Ticagrelor is a direct-acting P2Y12 receptor antagonist in a new chemical class called cyclopentyltriazolopyrimidines (CPTPs). Regarding possible interactions and side effects, please see full prescribing information.
On 6 December 2010, the European Commission granted marketing authorisation to ticagrelor, co-administered with acetylsalicylic acid (maintenance dose 75-150mg daily), for the prevention of atherothrombotic events in adult patients with ACS [unstable angina (UA), non—ST-segment elevation myocardial infarction (NSTEMI) or STEMI], including patients managed medically and those who are managed with percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG).
Ticagrelor is approved in 100 countries, including in the European Union under the trade name BRILIQUE and in the United States, Canada, Brazil, Australia and Russia under the trade name BRILINTA.
BRILINTA and BRILIQUE are trademarks of the AstraZeneca group of companies. For detailed information regarding ticagrelor in your area, please refer to the local prescribing information.
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 Data on file. ATLANTIC data will be presented as part of the European Society of Cardiology congress at 16:48 CEST on Monday, 1 September during the ‘Hotline’ session. It will also be part of the ‘Meet the Trialists’ session at 10:10 CEST on Tuesday, 2 September.
2 Chan M, Sun J et al. Long-Term Mortality of Patients Undergoing Cardiac Catheterization for ST-Elevation and Non-ST-Elevation Myocardial Infarction. American Heart Association. 2009; 3112.
3 Non-CABG-related and bleeding event according to PLATO criteria (composite of major and minor bleeds):
- - ≤ 48 hours after first dose p=0.87
- - > 48 hours and ≤ 30 days after first dose p=0.63