Trials of acute secondary prevention after minor stroke or transient ischemic attack (TIA), such as SOCRATES, POINT, and THALES, demonstrate a high initial rate of recurrence after ischemic events that drop quickly to a lower rate, suggesting a transient vulnerable clinical state, which may call for different treatments than the subsequent stabilized state. A kinetic model incorporating vulnerable and stabilized states provides estimates of the distinct kinetic rates reflecting the temporal features of underlying stroke mechanisms. We aimed to compare these kinetic rates between treatments and across trials, asking whether these features point to common pathophysiologic processes underlying stroke recurrence, and inform the targeting and timing of enhanced antiplatelet therapy in recurrent stroke prevention.

Kaplan-Meier recurrence-free survival curves in the SOCRATES, POINT, and THALES trials were estimated for each treatment group and fitted by nonlinear regression to the 2-state kinetic model, producing estimates of kinetic parameters, with standard errors estimated using the nonparametric bootstrap with repetitive resampling.

For each trial, the 2-state kinetic model fit the survival curves better than did the null (single-state) kinetic model or the Weibull model (p < 0.05). Recurrence rates in the vulnerable state (k₁) were 100-fold higher than in the stabilized state (k₂). Transition rates from the vulnerable to stabilized state (k₀) were still more rapid. Kinetic parameters were consistent across the trials, without significant differences between the trials. Enhanced antiplatelet regimens produced significant reductions in k₁ (aspirin alone: 0.030 ± 0.004 d^–1; active treatment: 0.016 ± 0.003 d^–1; p < 0.01) but did not affect k₀ or k₂, suggesting that active treatment only affected risk in the vulnerable state. Modeling based on these kinetic parameters suggests that most of the benefit of active treatment occurred within 3 days.

Across multiple trials of acute secondary prevention after minor stroke or TIA, recurrence of stroke is well-described by a 2-state kinetic model postulating vulnerable and stabilized states, with similar kinetic parameters across trials. Enhanced antiplatelet regimens only affected the recurrence rates in the vulnerable state, over a brief period. This analysis suggests that 2 distinct states follow acute cerebral ischemic events, subject to differential impact of immediate or delayed therapies.

轻微中风或短暂性脑缺血发作 (TIA) 后的急性二级预防试验，如 SOCRATES、POINT 和 THALES，表明缺血事件后初始复发率较高，但很快会下降到较低的复发率，表明临床处于短暂的脆弱状态。这可能需要与随后的稳定状态不同的治疗。结合脆弱状态和稳定状态的动力学模型提供了反映潜在中风机制的时间特征的不同动力学速率的估计。我们的目的是比较治疗之间和试验之间的这些动力学速率，询问这些特征是否指向中风复发的常见病理生理过程，并为预防复发性中风的增强抗血小板治疗的目标和时机提供信息。

SOCRATES、POINT 和 THALES 试验中的 Kaplan-Meier 无复发生存曲线针对每个治疗组进行了估计，并通过非线性回归拟合到 2 态动力学模型，生成动力学参数的估计值，并使用非参数引导程序估计标准误差通过重复重采样。

对于每个试验，2 态动力学模型比零（单态）动力学模型或 Weibull 模型更好地拟合生存曲线 ( p < 0.05)。脆弱状态 ( k ₁ ) 的复发率比稳定状态 ( k ₂ ) 高 100 倍。从脆弱状态到稳定状态（k ₀）的转变速度仍然更快。整个试验中的动力学参数是一致的，试验之间没有显着差异。强化抗血小板治疗方案使k ₁显着降低（单用阿司匹林：0.030 ± 0.004 d ^–1；积极治疗：0.016 ± 0.003 d ^–1；p < 0.01），但不影响k ₀或k ₂，表明积极治疗仅影响处于脆弱状态的风险。基于这些动力学参数的建模表明，积极治疗的大部分益处在 3 天内发生。

在轻微中风或 TIA 后急性二级预防的多项试验中，中风的复发可以通过假定脆弱状态和稳定状态的 2 态动力学模型得到很好的描述，并且各个试验中具有相似的动力学参数。加强抗血小板治疗仅在短时间内影响脆弱状态下的复发率。该分析表明，急性脑缺血事件后会出现两种不同的状态，受到立即或延迟治疗的不同影响。