AstraZeneca announced the results of the Phase 4 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 was presented during the European Society of Cardiology congress taking place in Barcelona.
Results of the ATLANTIC study were also published 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 catheterization 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 mortality.
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 risk.
“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, 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 program, 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 program, 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.
Date: September 1, 2014