FDA Expands Use of Ticagrelor to Patients Without History of MI or Stroke

The oral antiplatelet drug Ticagrelor (Brilinta, Astra Zeneca), was approved this week by the US Food and Drug Administration (FDA) for use in patients with coronary artery disease (CAD) who are at high risk for a first heart attack or stroke.

The drug had previously been 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.

The new approval expands the current use to include aspirin plus Brilinta dual antiplatelet therapy in patients who have a high CV risk, but without a history of heart attack or stroke.

The FDA approval was based on positive results from the Phase III THEMIS trial, which demonstrated a statistically significant reduction of cardiovascular events at 36 months in patients with CAD and type-2 diabetes (T2D) at high-risk of a first heart attack or stroke who were treated with aspirin plus Brilinta 60mg versus aspirin alone. 

The data from the THEMIS trial and the THEMIS-PCI sub-analysis were published in The New England Journal of Medicine and The Lancet respectively. 

The expansion of the drug approval has significant benefits for diabetic patients with heart disease, explained Gabriel Steg, MD, THEMIS trial Co-Chair and Professor at Université de Paris. 

“THEMIS for ticagrelor was a large, multi-national trial of more than 19,000 patients with coronary artery disease and type-2 diabetes. Around one third of patients with coronary artery disease have type-2 diabetes, putting them at higher risk of heart attack or stroke, than patients without diabetes,” said Steg. “Today’s approval brings new hope to patients at risk of experiencing a first heart attack or stroke.”

It also adds to the arsenal of treatment options for high risk heart disease patients without diabetes said Deepak L. Bhatt, THEMIS trial Co-Chair and Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital. 

“Coronary artery disease is a potentially life-threatening condition that causes significant morbidity in many people. The addition of ticagrelor to aspirin offers a new therapeutic option to decrease the likelihood of both heart attack and stroke, a significant advance in our ability to treat these high-risk patients.”

The THEMIS trial demonstrated the relative risk reduction of the composite endpoint of heart attack, stroke and CV death by 10% (absolute risk reduction; 0.8%, 7.7% vs 8.5%) 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. While this indication is not limited to this setting, the efficacy of Brilinta was established in a population with T2D in the THEMIS trial. The safety profile for Brilinta was consistent with the known profile of the medicine with an increased risk of bleeding events observed.

Regulatory submissions to expand the approved indication for Brilinta based on the THEMIS trial are also under regulatory review in the EU, Japan and China.