FDA OKs Ticagrelor Indication to Reduce Risk of First Heart Attack, Stroke in Patients With High-Risk CAD

June 1, 2020

This is the first regulatory approval for aspirin plus ticagrelor dual antiplatelet therapy for individuals with high cardiovascular risk but without prior instances of heart attack or stroke.

The FDA has approved ticagrelor (Brilinta, AstraZeneca) to reduce the risk of a first heart attack or stroke in high-risk individuals with coronary artery disease (CAD) but without a history of major adverse cardiovascular events (MACE).

Ticagrelor is an oral, reversibly binding, direct-acting P2Y12 receptor antagonist that inhibits platelet activation. Ticagrelor plus aspirin significantly reduces the risk of MACE, including myocardial infarction (MI), stroke, or CV-related death in individuals with acute coronary syndrome (ACS) or a history of MI.

FDA approval of this new indication was based on results from the THEMIS trial and the THEMIS-PCI sub-analysis, published in The New England Journal of Medicine and The Lancet respectively.

The multi-national, randomized, double-blind phase 3 THEMIS trial incorporated more than 19,000 patients across 42 countries in Europe, Asia, Africa, North and South America with CAD and type 2 diabetes (T2D) who did not have a history of heart attack or stroke. Participants were randomized to receive 60 mg of ticagrelor plus aspirin twice daily in order to evaluate the safety and efficacy of the therapy.

Trial results provided significant support for ticagrelor plus aspirin therapy for this subset of patients; the trial demonstrated the relative risk reduction of the composite end point of heart attack, stroke, and CV death by 10% (absolute risk reduction; 0.8%, 7.7% versus 8.5%) with aspirin plus long-term ticagrelor compared with aspirin alone for patients with CAD and T2D without a history of heart attack or stroke.

The most frequently appearing (>5%) adverse events (AEs) included bleeding and dyspnea, according to the investigators.

AstraZeneca also recently announced the high-level results from its phase 3 THALES trial, which assessed aspirin plus ticagrelor 60 mg in reducing the risk of the composite of stroke and death at 30 days after an acute ischemic stroke or transient ischemic attack compared with aspirin alone.

Ruud Dobber, executive vice president, BioPharmaceuticals Business Unit, said: “Today’s approval of BRILINTA is important news for patients with coronary artery disease who will now have a new therapy option to reduce the risk of a first heart attack or stroke. This new indication is a further testament to the overwhelming science supporting BRILINTA in the management of patients with coronary artery disease at high risk for cardiovascular events.”

References:

1. BRILINTA approved in the US to reduce the risk of a first heart-attack or stroke in high-risk patients with coronary artery disease. News Release. AstraZeneca; June 1, 2020. Accessed June 1, 2020. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2020/brilinta-approved-in-the-us-to-reduce-the-risk-of-a-first-heart-attack-or-stroke-in-high-risk-patients-with-coronary-artery-disease-06012020.html.
2. Steg PG, Bhatt DL, Simon T, et al. Ticagrelor in Patients with Stable Coronary Disease and Diabetes. New England Journal of Medicine. 2019. Doi: 10.1056/NEJMoa1908077