New Brilinta indication expands treatment to patients at high-risk of developing an atherothrombotic event
AstraZeneca’s Brilinta (ticagrelor), co-administered with low-dose acetylsalicylic acid (ASA: 75-150 mg), has been approved in Canada to reduce the risk of a first heart attack or stroke in patients with coronary artery disease (CAD) and type-2 diabetes (T2D) who have a history of percutaneous coronary intervention (PCI) and are at high-risk of developing an atherothrombotic event.
The approval by Health Canada was based on positive results from THEMIS-PCI, a sub-analysis of the Phase III THEMIS trial representing 58% of the overall trial population. In THEMIS-PCI, fewer events of the composite of cardiovascular death, heart attack and stroke (corresponding to a 15% relative risk reduction, 1.2% absolute risk reduction), was observed for aspirin plus Brilinta compared with aspirin alone.1,2 The effect was driven by fewer heart attacks and strokes with Brilinta.1 The safety profile for Brilinta was consistent with the known profile of the medicine with an increased risk of bleeding events observed.2,3
Shamir R. Mehta, MD, MSc, FRCPC, FACC, FESC, THEMIS trial Executive Committee Member, Professor of Medicine at McMaster University in Hamilton, and Director of the interventional cardiology program at Hamilton Health Sciences, Ontario, Canada said: “It is established that there is a high cardiovascular risk in patients with stable coronary artery disease and diabetes. THEMIS-PCI has established a new option for dual antiplatelet therapy with ticagrelor in patients with coronary artery disease and diabetes, who have a history of PCI.”
Deepak L. Bhatt, MD, MPH, THEMIS trial Co-Chair, Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital, and Professor of Medicine at Harvard Medical School, Boston, US said: “Coronary artery disease is a potentially life-threatening condition that causes significant morbidity in many people. In those patients with diabetes who have a history of PCI, the addition of ticagrelor to aspirin offers a new therapeutic option to decrease the likelihood of both heart attack and stroke. This approval in Canada is a significant advance in our ability to treat these high-risk patients.”
Gabriel Steg, MD, THEMIS trial Co-Chair and Professor at Université de Paris, said: “THEMIS for ticagrelor was a large, multi-national trial of more than 19,000 patients with coronary artery disease and type-2 diabetes. Of these patients, 11,154 had a history of PCI, representing a large and easily identifiable population in clinical practice. This approval in Canada brings new hope to patients who have previously undergone PCI and are at risk of experiencing a first heart attack or stroke.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “This approval in Canada is a further demonstration of AstraZeneca’s commitment to realizing the benefits of Brilinta in the management of coronary artery disease and type-2 diabetes in patients at high-risk for a first cardiovascular event. It follows the recent approval in the US to reduce the risk of a first heart attack or stroke in high-risk patients with coronary artery disease.”
The THEMIS trial demonstrated the relative risk reduction of the composite endpoint of heart attack, stroke and CV death by 10% (absolute risk reduction 0.7%; 36-months KM% 6.9 vs 7.6%) with aspirin plus long-term Brilinta compared to aspirin alone in patients who had CAD and T2D without a history of heart attack or stroke.3
Brilinta is approved in more than 110 countries for the prevention of atherothrombotic events in adult patients with acute coronary syndrome (ACS), and in more than 70 countries for the secondary prevention of CV events among high-risk patients who have experienced a prior myocardial infarction.
CAD and T2D
CAD is the most common type of heart disease. Ischaemic heart disease is the leading cause of healthy life years lost due to disability in men and the second cause in women worldwide.4,5 The disease burden of atherosclerosis is significantly higher in patients with CAD and T2D than in CAD patients without T2D.6
THEMIS is an AstraZeneca-sponsored, multi-national, randomized, double?blinded Phase IIIb trial in patients with CAD and T2D with no prior heart attack or stroke. More than 19,000 patients were randomized across 42 countries in Europe, Asia, Africa, North and South America. THEMIS was designed to test the hypothesis that aspirin plus Brilinta twice daily would reduce MACE (major adverse cardiac events), compared with aspirin alone. CAD was defined as PCI, bypass surgery, or at least a 50% narrowing of a coronary artery. Additionally, THEMIS-PCI is a clinically meaningful and prespecified sub-analysis of patients (11,154 which is 58% of total patients) who had previously undergone PCI.7
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 MACE defined as myocardial infarction (MI, heart attack), stroke or CV death, in patients with ACS or a history of MI.
Brilinta, co-administered with low dose aspirin (ASA: 75-150 mg), 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.
1. Bhatt D.L et al. Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): A phase 3, placebo-controlled, randomised trial. Lancet 2019; 394:1169
2. Steg P.G et al. Ticagrelor in Patients with Stable Coronary Disease and Diabetes. N Engl J Med 2019; 381:1309-1320.
3. AstraZeneca Canada Inc., BRILINTA? (Ticagrelor), Product Monograph. Accessed August 26, 2020, available at: http://www.aionspain.com/en/our-medicines.html.
4. NIH National Heart, Lung, and Blood Institute. Ischemic heart disease: Also known as coronary artery disease, coronary heart disease, coronary microvascular disease [cited 2019 Feb 4]. Available from: URL: https://www.nhlbi.nih.gov/health-topics/ischemic-heart-disease.
5. Kyu HH et al. Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392(10159):1859–922.
6. Arnold S.V. et al. Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: A scientific statement from the American Heart Association. Circulation. 2020; 141:e779–e806.
7. Bhatt D.L and Steg P.G. THEMIS and THEMIS-PCI: New Option for Antiplatelet Therapy in Patients with Stable Atherosclerosis and Diabetes: Key Findings from THEMIS and THEMIS-PCI. Eur Heart J. 2019; 40(41):3378–3381.