Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
Department of Epidemiology, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
Int J Stroke. 2024 Apr;19(4):414-421. doi: 10.1177/17474930231225568. Epub 2024 Jan 8.
In stroke patients with insulin resistance (IR), post-stroke cognitive impairment (PSCI) is associated with higher risk of recurrent stroke, but the effect of pioglitazone on that risk has not been explored. The goal of this study was to compare the secondary stroke prevention effect of pioglitazone against placebo in patients with versus without PSCI.
We studied patients enrolled in the Insulin Resistance Intervention after Stroke (IRIS) trial with a post-stroke modified Mini-Mental State Examination (3MS) cognitive assessment (mean time of assessment: 79 days post-stroke). We considered a baseline score of ⩽ 88 on the 3MS to indicate global PSCI, and domain-specific summary scores in the lowest quartile to indicate attention, language, memory, orientation, and visuospatial impairments.
In n = 3338 patients with IR, the effect of pioglitazone versus placebo on secondary stroke significantly differed by initial post-stroke global (interaction p = 0.0127) and memory impairment status (interaction p = 0.0003). Hazard ratios (HRs) were time-dependent such that, among those with either global or memory impairment, pioglitazone has an increasingly stronger protective effect at later timepoints. There was no statistically significant effect of pioglitazone among those without either global or memory impairment. The effect of pioglitazone versus placebo on myocardial infarction (MI) also significantly differed by global impairment status (interaction p = 0.030). Pioglitazone was protective among those with global impairment (HR = 0.23 [95% CI: 0.08, 0.71]) but not among those without (HR = 0.88 [95% CI: 0.59, 1.31]).
These data indicate that pioglitazone treatment may be more effective at reducing risk of recurrent stroke and MI in stroke patients with PSCI. Simple cognitive testing 2-3 months post-stroke may identify patients for whom treatment would be most beneficial.
在患有胰岛素抵抗（IR）的中风患者中，中风后认知障碍（PSCI）与复发性中风的风险增加相关，但尚未探讨吡格列酮对该风险的影响。本研究的目的是比较吡格列酮与安慰剂在有或无 PSCI 的患者中的二级中风预防效果。
我们研究了参加胰岛素抵抗干预后的中风（IRIS）试验的患者，这些患者在中风后进行了改良的简易精神状态检查（3MS）认知评估（评估的平均时间：中风后 79 天）。我们将基线 3MS 评分 ⩽88 定义为全球 PSCI，将最低四分位数的特定领域综合评分定义为注意力、语言、记忆、定向和视空间障碍。
在 n=3338 名患有 IR 的患者中，吡格列酮与安慰剂对二级中风的影响因初始中风后全球（交互作用 p=0.0127）和记忆障碍状态（交互作用 p=0.0003）而异。风险比（HRs）是时间依赖性的，因此，在那些存在全球或记忆障碍的患者中，吡格列酮在稍后的时间点具有越来越强的保护作用。在那些既没有全球也没有记忆障碍的患者中，吡格列酮没有统计学上的显著效果。吡格列酮与安慰剂对心肌梗死（MI）的影响也因全球受损状态而显著不同（交互作用 p=0.030）。吡格列酮在全球受损的患者中具有保护作用（HR=0.23 [95%CI：0.08，0.71]），但在没有受损的患者中没有保护作用（HR=0.88 [95%CI：0.59，1.31]）。
这些数据表明，吡格列酮治疗可能更有效地降低 PSCI 中风患者复发性中风和 MI 的风险。中风后 2-3 个月进行简单的认知测试可能会识别出最受益于治疗的患者。
