In THALES, Brilinta reduced the total burden of disability due to ischaemic stroke recurrence
Sub-analysis data were presented alongside full trial results at ESO-WSO 2020
Detailed results from a prespecified exploratory analysis of the positive THALES Phase III trial showed Brilinta (ticagrelor) 90mg, used twice daily and taken with daily aspirin for 30 days, reduced the rate of the composite of disabling stroke or death by 17% (absolute risk reduction 0.7%, hazard ratio (HR) 0.83 [95% confidence interval (CI) 0.69, 0.99], nominal p=0.039) compared to aspirin alone, in patients who had an acute ischaemic stroke or transient ischaemic attack (TIA).1
The rate of the composite of non-disabling stroke or death at 30 days was 1.3% in the aspirin plus ticagrelor group and 1.6% in the aspirin only group (HR 0.79 [95% CI 0.57, 1.08], p=0.140).1 Following a recurrent stroke, patients treated with aspirin plus ticagrelor experienced a nominally significant reduction of disability burden compared to aspirin alone, based on an analysis of modified Rankin score (OR 0.77 [95%CI 0.65, 0.91], nominal p=0.002).1 These new findings reinforce results of the Phase III THALES trial showing a statistically significant and clinically meaningful reduction in the composite of stroke or death at 30 days in patients with a stroke or TIA receiving aspirin plus ticagrelor versus aspirin alone.
Prof Pierre Amarenco, International Coordinating Investigator and Vice-Chair of the THALES Executive Committee and Professor of Neurology at Paris University, said: “Until now, only aspirin had shown a significant reduction in disabling stroke during the first 90 days following an ischaemic stroke in a single trial. These new findings from THALES show that aspirin plus ticagrelor could provide a clinically meaningful reduction of the composite of disabling stroke and death compared to aspirin alone at day 30 due to subsequent ischaemic stroke.”
Dr Clay Johnston, International Coordinating Investigator and Chair of the THALES Executive Committee and Dean of the Dell Medical School at The University of Texas in Austin, US, said: “Without early treatment, up to 10 per cent of people are at risk of a major stroke in the first month after a transient ischaemic attack or acute ischaemic stroke. The THALES trial demonstrated that the risk of the composite of stroke or death at 30 days was lower with aspirin-ticagrelor than with aspirin alone.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “The use and benefit of ticagrelor in cardiovascular disease is well established, and the same mode of action results in reducing the risk of a subsequent stroke. The THALES data presented at ESO-WSO 2020 further support the initial trial findings and reflect our commitment to transform patient outcomes in stroke by providing a new treatment option with the potential to deliver clinically meaningful improvements.”
Key efficacy and safety data from the exploratory analysis of the THALES trial
i. Amarenco P et al. Ticagrelor added to aspirin in acute ischemic stroke or TIA in prevention of disabling stroke: a randomized clinical trial. JAMA Neurol. doi:10.1001/jamaneurol.2020.4396
* By GUSTO (Global Utilization of Streptokinase and Tissue-type plasminogen activator for Occluded coronary arteries) definition; CI=confidence interval; KM=Kaplan-Meier; mRS=modified Rankin Scale
The risk for severe bleeding events in patients with disabling stroke was 0.4% in the aspirin plus ticagrelor group and 0.1% in the aspirin group.1 The results were in line with the known safety profile of ticagrelor.
Results from this sub-analysis were presented alongside full results from the THALES trial on 7 November 2020 at the virtual European Stroke Organisation and the World Stroke Organization Conference 2020 and published simultaneously in JAMA Neurology.
Earlier this month, AstraZeneca announced that the US Food and Drug Administration (FDA) approved ticagrelor to reduce the risk of stroke in patients with an acute ischaemic stroke (National Institutes of Health Stroke Scale score ≤5) or high-risk TIA.
An ischaemic stroke is caused by a blockage cutting off the blood supply to a region of the brain. A transient ischaemic attack, is a temporary blockage of the blood supply to a region of the brain, resulting in symptoms only lasting for a short amount of time. Stroke is a leading cause of disability and death worldwide.2 In the US, someone has a stroke every 40 seconds, and every four minutes, someone dies of stroke.3 About one in four strokes are recurrent, with the risk particularly high within 30 days after the initial event and even higher when looking at time periods closer to the initial event.4,5
THALES is an AstraZeneca-sponsored, randomised, placebo-controlled, double-blinded, international, multicentre, event-driven trial involving more than 11,000 patients from 28 countries. It tested the hypothesis whether aspirin plus ticagrelor is superior to aspirin alone in preventing the composite of stroke and death in patients with non-cardioembolic acute ischaemic stroke or high-risk TIA. Patients were randomised within 24 hours of onset of acute ischaemic stroke or high-risk TIA symptoms and treated for 30 days. Study treatments were ticagrelor 180mg loading dose on day 1, followed by 90mg twice daily on days 2–30, or matching placebo. All patients received open-label aspirin 300–325mg on day 1, followed by 75–100mg once daily on days 2–30. The primary efficacy outcome was the time to the composite endpoint of stroke and death at 30 days. The primary safety outcome is time to first severe bleeding event according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) definition, which includes fatal bleedings, intracranial haemorrhage; and bleeding causing hemodynamic compromise requiring intervention. In the overall population ticagrelor taken with daily aspirin for 30 days, reduced the rate of the primary composite endpoint of stroke and death by 17% (absolute risk reduction 1.1%; HR 0.83 [95% CI 0.71, 0.96], p=0.02), compared to aspirin alone.
Brilinta (ticagrelor) is an oral, reversible, direct-acting P2Y12 receptor antagonist that works by inhibiting platelet activation. Ticagrelor, together with aspirin, has been shown to significantly reduce the risk of major adverse cardiovascular (CV) events (heart attack, stroke or CV death), in patients with acute coronary syndrome (ACS) or a history of heart attack. In the US, ticagrelor is also indicated for the reduction of the risk of a first heart attack or stroke in high-risk patients with coronary artery disease.
In the EU ticagrelor, co-administered with aspirin, is indicated for the prevention of atherothrombotic events in adult patients with ACS, or for patients with a history of heart attack and a high risk of developing an atherothrombotic event.
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM) together forms one of AstraZeneca’s three therapy areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys 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. The Company’s 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.
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1. Amarenco P et al. Ticagrelor added to aspirin in acute ischemic stroke or TIA in prevention of disabling stroke: a randomized clinical trial. JAMA Neurol. Published online November 7 2020; doi:10.1001/jamaneurol.20204396
2. GBD 2017. Causes of Death Collaborators 2018. Global, regional, and national age-sex specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392:1736-88.
3. Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics—2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139–e596.
4. Hankey GJ. Secondary stroke prevention. Lancet Neurol 2014; 13(2):178–94.
5. Coull AJ, Lovett JK, and Rothwell PM. Population based study of early risk of stroke after transient ischaemic attack or minor stroke: implications for public education and organisation of services. BMJ. 2004;328:326.