Risk Factors for Intracranial Hemorrhage in the THEMIS Trial: A Comprehensive Secondary Analysis

Coronary artery disease (CAD) occurs when the arteries that supply blood to the heart become narrowed or blocked by fatty deposits, reducing blood flow to the heart muscle. Many people with CAD also have type 2 diabetes, a condition in which the body cannot properly control blood sugar. Millions of people worldwide have these conditions. These individuals have a particularly high risk of heart attacks and strokes (where the blood supply to part of the brain is blocked or reduced). To reduce this risk, doctors often prescribe medicines that prevent blood clots. One such medicine is ticagrelor, which is commonly used together with aspirin. These medicines help stop platelets (small blood cells involved in clotting) from sticking together and forming harmful clots.

However, medicines that reduce clotting can also increase the risk of bleeding. One of the most serious forms of bleeding is intracranial hemorrhage (ICH), which means bleeding inside the skull or brain. At present, doctors do not fully understand which patients are most likely to experience this type of bleeding while taking ticagrelor and aspirin. Better understanding of these risks could help doctors make safer treatment decisions.

In this project, we will analyse data from the THEMIS trial. This was a large clinical trial that compared ticagrelor plus aspirin with placebo (an inactive treatment) plus aspirin in people with stable CAD and type 2 diabetes. Because the trial collected detailed information about participants’ health and outcomes, it provides a valuable opportunity to study the risk of intracranial bleeding.

Our research will focus on identifying characteristics present at the start of the trial that may increase the risk of ICH during treatment. These characteristics may include factors such as age, blood pressure and kidney function. We will also examine whether different types of ICH, such as bleeding caused by injury (traumatic), bleeding that occurs without injury (spontaneous), or bleeding related to medical procedures (procedural)—have different risk factors.

We will analyze the data from the THEMIS trial using statistical methods to examine how patient characteristics relate to the timing and occurrence of ICH during the study period. Using these findings, we will develop a prediction tool that estimates an individual patient’s risk of intracranial bleeding based on their baseline health information. We will also test the reliability of this prediction tool.

By identifying patients who may be at higher risk of intracranial hemorrhage, this research will help improve the safety of treatments that prevent blood clots. The results may help doctors better balance the benefits and risks of medicines such as ticagrelor and aspirin, and support more personalised treatment decisions for people with heart disease such as CAD and diabetes.