Abstract TMP26: Effect Of Pioglitazone On Recurrent Stroke Risk In Patients With Post-stroke Cognitive Impairment And Insulin Resistance: Subgroup Analysis Of IRIS Trial

Abstract

Patients with post-stroke cognitive impairment are at higher risk of recurrent stroke but the effect of pioglitazone on that risk has not been explored. The goal of this study was to determine the effect of pioglitazone on the risk of recurrent vascular events in patients with post-stroke cognitive impairment (PSCI) and insulin resistance (IR). We studied patients enrolled in Insulin Resistance Intervention after Stroke (IRIS) trial with a baseline Modified Mini-Mental State Examination (3MS) cognitive exam at median of 79 days after their 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 language, attention, orientation, memory and visuospatial impairments. The primary endpoint of the study was recurrent stroke and MI. We studied n=3,338 patients. In fully adjusted Cox proportional hazards models for recurrent stroke, the hazard ratio (HR) for the effect of pioglitazone compared to placebo differed by post-stroke memory impiarment status (interaction p = 0.01). Pioglitazone was associated with 51% lower risk of recurrent stroke in patients with post-stroke memory impairment [HR = 0.49 (95% CI: 0.30 - 0.81); p = 0.005], but not in those without it [HR = 1.01 (95% CI: 0.75- 1.36); p = 0.942]. In fully adjusted Cox proportional hazards models for MI, the HR for the effect of pioglitazone compared to placebo differed by global PSCI status (interaction p = 0.03). Pioglitazone was associated with 77% lower risk of MI in patients with post-stroke global PSCI [HR = 0.23 (95% CI: 0.08, 0.71); p = 0.01], but not in those without it [HR = 0.88 (95% CI: 0.59, 1.31); p = 0.53]. These data indicate that simple cognitive testing after 3 months from stroke may serve as a precision medicine tool to identify patients at higher risk who may benefit from pioglitazone treatment. This approach can be tested in secondary stroke prevention clinical trials.