Acute ischemic stroke, a condition where a blockage in an artery disrupts blood flow to the brain, requires rapid treatment to prevent severe damage or death. Treatments like tissue-plasminogen activator (tPA), or alteplase, can be incredibly effective, dissolving the clot and restoring blood flow. However, patients on blood thinners such as warfarin – common among those at risk for stroke and heart attack – are often excluded from receiving this lifesaving drug because they have been excluded in clinical studies.
Ying Xian, M.D., Ph.D., FAHA
Associate Professor of Neurology
UT Southwestern Medical Center
Ying Xian, M.D., Ph.D., FAHA, Associate Professor of Neurology at UT Southwestern Medical Center, seeks to change that for better patient outcomes.
“Back in 2010, I found there are many gaps in stroke guideline recommendations because they are not based on the highest level of evidence and, in fact, are informed by small observational studies, case reports, or even expert opinions,” said Dr. Xian, who is also Section Head, Stroke and Cerebrovascular Diseases in the Department of Neurology at UTSW.
With stroke being one of the leading causes of disability and mortality in this country, Dr. Xian’s work is paving the way for the wider adoption of alteplase, the only FDA-approved medical therapy for acute ischemic stroke. Quick treatment is critical. With every minute of delay, about 2 million neurons die. The intent to keep patients safe due to fairly uncommon bleeding risks or other contraindications does the opposite. It leads to their exclusion from lifesaving, life-preserving treatments like alteplase.
Historically, patients with high stroke severity scores or those older than 80 were often excluded from research studies. They are also commonly prescribed oral anticoagulants. Consequently, when the FDA approved medications like alteplase, these exclusion criteria shaped treatment guidelines. Unfortunately, this lack of inclusion means there is no evidence to support the effectiveness or known risks of these treatments in these specific patient groups. Better decision-making for all stroke patients is the crux of Dr. Xian’s research.
“Fortunately, we have access to data from the nationwide stroke registry, known as the Get With The Guidelines Stroke Program, through the American Heart Association,” he said. “This allows us to examine patients treated with tPA, including those who were on warfarin before their stroke. Our findings show that there is no significant risk of bleeding. However, many patients were previously excluded from this lifesaving treatment, resulting in long-term disabilities, which could be avoided. It’s a very unfortunate situation.”
Even today, new drugs face similar challenges. Dr. Xian is very interested in off-label, or off-guideline, treatments for patients with acute ischemic stroke. Historically, warfarin was the primary anticoagulant, but now direct oral anticoagulants (DOACs) like dabigatran, rivaroxaban, apixaban, and edoxaban, which are safer and easier to use, are more common. But because these newer drugs also were not available during earlier randomized clinical trials, current guidelines advise against treating patients on these medications due to perceived high risk of bleeding complications.
Similarly, his dual antiplatelet therapy study shine a light on the large variation in secondary stroke prevention in U.S. practice, showing that 50% of patients with minor ischemic strokes didn’t receive guideline recommended antiplatelet therapy for secondary stroke prevention, suggesting potential underuse of the treatment. In contrast, more than 40% of patients with nonminor strokes were prescribed dual antiplatelet therapy at discharge, suggesting potential overuse of the treatment and even harm to the stroke survivors.
Significant research is still needed to update stroke guidelines and improve patient outcomes. Dr. Xian is taking this further by focusing on the future care of stroke survivors, particularly concerning cognitive impairment – a major concern for both survivors and their caregivers. Unfortunately, limited data on this topic exists, as most studies are either single-center or small cohort studies that are not nationally representative. This new research endeavor aims to determine how often patients develop dementia after a stroke, which remains largely unknown. Additionally, it seeks to identify the risk factors associated with dementia, such as hypertension, hyperlipidemia, or preexisting cardiovascular disease, and, most importantly, protective factors that could prevent cognitive impairment post-stroke.
Dr. Xian and his colleagues at UT Southwestern consider patient perspectives as well. For example, while health care professionals often focus on functional outcomes for stroke patients, many struggle with memory disorders after a stroke. Their input helps identify research questions that are most relevant to stroke survivors and helps doctors explain findings in ways they can understand. This collaboration helps disseminate research results to the patient community effectively. It’s a reciprocal relationship where key insights are shared and the research is enhanced, ultimately improving patient care and outcomes.
Much of the current treatment is standardized, where specific medications are prescribed universally to treat stroke. However, each patient is unique, with their own risk profiles and personal characteristics. Dr. Xian’s work represents the next frontier in stroke research, shaping guidelines and empowering physicians to revolutionize stroke treatments to meet the specific needs and preferences of each patient and significantly enhance outcomes.