Two-State Kinetic Model of Rates of Stroke Recurrence in the POINT Study Population

Abstract

Background and Purpose: Following an acute ischemic stroke or transient ischemic attack, 2 rates of stroke recurrence are suggested by data from trials of acute secondary prevention treatments: a transient rapid rate followed by a persisting slower rate of stroke. Methods: A kinetic model was constructed based on underlying vulnerable and stabilized states of patients following acute ischemic events related by fixed transition rates. Its predictions were fitted by nonlinear regression to the observed timing of outcome events in patients in the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke). Results: The modeled survivor function produced a close fit to the observed data. The model's predicted kinetic rates suggest that, among subjects in the control group, the event rate was 100-fold higher in the vulnerable state than in the stabilized state. Active treatment halved this rapid rate and had little effect on event rates in the stabilized state. If at least one-tenth of the study population began in the vulnerable state, the rate of transition from the vulnerable to the stabilized state was still faster, with a half-life of only 1 to 2 days. Conclusions: Examination of kinetics of stroke occurrence, and of the rates associated with modeled state transitions, may provide insights into the underlying pathophysiological events that are targets for acute secondary prevention of stroke.