Ticagrelor DAPT Wins FDA Approval to Reduce Risk of First CV Event in High-risk Patients

June 5, 2020

THEMIS trial results showed a statistically significant reduction in risk of MACE with ticagrelor plus aspirin vs aspirin alone in patients with CAD at high risk of first heart attack or stroke.

The FDA granted a label expansion this week for ticagrelor (Brilinta, AstraZeneca) to reduce the risk of a first heart attack or stroke in high-risk patients with coronary artery disease (CAD). It is the first regulatory approval for the dual antiplatelet combination of aspirin plus ticagrelor in patients with high risk for, but no history of, heart attack or stroke, according to an AstraZeneca statement.

“Coronary artery disease is a potentially life-threatening condition that causes significant morbidity in many people," said Deepak Bhatt, MD, MPH, THEMIS trial co-chair and executive director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital, in the company statement. "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."


FDA approval of the oral P2Y12 inhibitor for the new indication was based on positive results from the multinational phase 3 THEMIS trial conducted in patients with CAD and type 2 diabetes (T2D) without prior heart attack or stroke. l. THEMIS randomized more than 19,000 patients and over nearly 2 years of follow up examined the impact of dual antiplatelet therapy with aspirin plus ticagrelor or aspirin on the primary composite endpoint of major adverse cardiac events (MACE [heart attack, stroke, CV death]).

THEMIS demonstrated a relative risk reduction (RR) in MACE of 10% (absolute RR; 0.8% [7.7% vs 8.5%]) with aspirin plus long-term ticagrelor vs aspirin alone in patients who had CAD and T2D without a history of heart attack or stroke. The primary composite endpoint was driven by a reduction in heart attack and stroke.

“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 Gabriel Steg, MD, THEMIS trial co-chair and professor at Université de Paris, in the news release. “Today’s approval brings new hope to patients at risk of experiencing a first heart attack or stroke.”

Label information for ticagrelor highlights an increased bleeding risk, similar to other antiplatelet agents, that can result in significant and sometimes fatal bleeding. Ticagrelor is also contraindicated in those with active pathological bleeding or history of intracranial hemorrhage. Labeling information also recommends against initiating therapy in those undergoing urgent coronary artery bypass graft surgery.

Ticagrelor is an oral, reversibly binding, 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 events (myocardial infarction, stroke, or CV death) in patients with acute coronary syndrome or a history of MI.