Date: 2014-09-01
Type of information: Publication of results in a medical journal
phase: 4
Announcement: publication of results in the New England Journal of Medicine
Company: AstraZeneca (UK)
Product: Brilinta®/Brilique™ (ticagrelor)
Action
mechanism: platelet aggregation inhibitor. Brilinta® (ticagrelor) is a direct-acting P2Y12 receptor antagonist in a chemical class called cyclo-pentyl-triazolo-pyrimidines (CPTPs). It 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).
Disease: reduction of heart attacks and cardiovascular death in patients with acute coronary syndrome
Therapeutic area: Cardiovascular diseases
Country:
Trial
details: 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) is 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 pre-percutaneous coronary intervention. 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.
Latest
news: * On September 1, 2014, AstraZeneca 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 have been published in The New England Journal of Medicine. They will also be presented during the European Society of Cardiology congress1 taking place between 30 August and 3 September 2014 in Barcelona. 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 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.
