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Vivli Researcher Spotlight: Examining survivor function data across multiple trials for kinetics of stroke recurrence

James Brorson is a professor of neurology at the University of Chicago, with a research focus on vascular neurology. He has more than 25 years of patient care experience, as well as laboratory and clinical research. He has served as a principal investigator for several clinical trials in secondary stroke prevention, and currently serves as medical director of the University of Chicago Comprehensive Stroke Center, which cares for more than 400 stroke patients annually.  

Dr. Brorson’s team submitted a research proposal to access Vivli to conduct analysis relevant to their topic, “Examination of survivor functions from SOCRATES and THALES trials for kinetics of stroke recurrence.” The team’s completed research has recently been presented to the research community in publications including Neurology and Stroke

Stroke is a common and often devastating condition in which blockage of blood flow to a part of the brain leads to its destruction, with corresponding loss of function, producing a variety of symptoms. Stroke is a leading cause of death and long-term disability globally. In the United States, some 800,000 persons suffer strokes each year, and more than 100,000 die.

A person who suffers a first stroke classified as mild is at increased risk of a second, often more severe stroke. The risk of recurrence is highest in the immediate aftermath of the first stroke, and prevention efforts frequently concentrate in the 12-24 hour period following the first incident. The rate of recurrence declines over time, and researchers have theorized that examination of the time course for the timing and rates of stroke recurrence may provide insight which may help with devising better ways to prevent recurrent strokes. 

Dr. James Brorson and a team of colleagues set out to harmonize, merge, and assess data gathered from participants in three large trials in the aftermath of a first stroke event. Their aim was to determine whether treatment decisions could be made more precisely based upon analysis of timing and rates of stroke recurrence. They accessed data from more than 25,000 participants in order to provide sufficient statistical power to detect modifiers of early and late kinetics of stroke recurrence.

To carry out their analysis, the team developed a two-state kinetic model of stroke recurrence. This model proposes an initial vulnerable state with a higher rate of stroke recurrence, which rapidly transitions to a stabilized state with a lower rate of recurrence. They further theorized that this model would fit the survival data for each of these recent trials of acute secondary prevention better than would a model assuming only a single clinical state after the initial minor stroke.

The team’s findings established that recurrence of stroke is well-described by a two-state kinetic model postulating vulnerable and stabilized states, with similar kinetic parameters across the three trials. Their analysis also indicates that enhanced antiplatelet regimens only affected the recurrence rates during a brief period in the vulnerable state. This suggests that two distinct states follow acute cerebral ischemic events, and that these states are subject to differential impact of immediate or delayed therapies. 

These findings have been published in the academic journals Neurology and Stroke. The authors are also working on a second phase of this project to harmonize and curate the data from the first phase into a single large dataset. When complete, they plan to re-share this dataset on the Vivli data repository to support further research in this area, providing additional opportunities for analysis and identification of new methods to prevent stroke recurrence.

 

Read more about Dr. Brorson’s research:

Examination of survivor functions from SOCRATES and THALES trials for kinetics of stroke recurrence (Vivli Research Request 6550)

Vulnerable and Stabilized States After Cerebral Ischemic Events: Implications of Kinetic Modeling in the SOCRATES, POINT, and THALES Trials (Neurology

Abstract WMP61: Vulnerable And Stabilized States After Cerebral Ischemic Events: Implications Of Kinetic Modeling In The POINT, SOCRATES, And THALES Trials (Stroke)

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