Risk–Benefit of Ticagrelor by Anterior vs Posterior Circulation Ischemia: A Pooled Secondary Analysis of THALES and SOCRATES

Blood flow problems in the brain can lead to serious conditions such as a stroke or a transient ischemic attack (TIA), often called a “mini-stroke.” These events happen when blood supply to part of the brain is suddenly reduced or blocked. Stroke is a leading cause of disability and death worldwide, affecting millions of people each year. The brain is commonly divided into two main blood supply areas: the anterior circulation (which supplies the front parts of the brain, important for speech, movement, and thinking) and the posterior circulation (which supplies the back parts of the brain, important for balance, vision, and coordination). Problems in these two areas can cause different symptoms and may respond differently to treatment.

In this study, we will evaluate how well a medication called ticagrelor works and how safe it is for people who have had an ischemic stroke or TIA affecting either the anterior or posterior circulation. Ticagrelor is a blood-thinning medication that helps prevent blood clots from forming, which can reduce the chance of another stroke. However, blood-thinning drugs can also increase the risk of bleeding, including bleeding in the brain.

We will use existing data from two large clinical trials: THALES (Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death) and SOCRATES (Acute Stroke or Transient Ischaemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes). These trials previously studied ticagrelor in people with recent stroke or TIA, but they did not fully examine whether its benefits and risks differ depending on which part of the brain was affected.

Our primary objective will be to determine whether ticagrelor is more or less effective at preventing repeat strokes in anterior circulation events compared with posterior circulation events, and whether the risk of serious bleeding differs between these two groups. We will also examine the net clinical benefit, meaning the balance between reducing future strokes and increasing bleeding risk.

We will conduct this research by re-analyzing patient data from the THALES and SOCRATES trials. We will compare outcomes such as recurrent stroke, death, and major bleeding between patients with anterior circulation ischemia and those with posterior circulation ischemia. This approach allows us to answer important clinical questions without exposing new patients to risk.

By understanding whether ticagrelor works differently depending on the brain region involved, we hope this research will help doctors make more personalized treatment decisions, improve stroke prevention, and reduce harm for patients who are at high risk of another stroke.