Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Ann Neurol. 2012 Nov;72(5):799-806. doi: 10.1002/ana.23680.
Disability or death occurs more frequently in patients with hemorrhagic transformation (HT) after ischemic stroke. In rat models of stroke, sulfonylurea (SU) drugs such as glibenclamide (adopted US name, glyburide) confer protection against swelling and HT through actions on the novel SUR1-regulated NC(Ca-ATP) channel. Here, we sought to determine whether the use of SU drugs in patients with diabetes mellitus (DM) presenting with acute ischemic stroke might influence the incidence of HT.
We retrospectively analyzed data on 220 patients with DM who presented with acute ischemic stroke, 43 of whom were managed with and continued to receive SU drugs, and 177 of whom were managed without (controls).
During a median length of stay in hospital of 11 days, 20 control patients (11%) experienced symptomatic HT (sHT), whereas no patient in the SU group experienced sHT (p = 0.016). No patient in the SU group died, compared to 18 (10%) in the control group (p = 0.027). Similarly favorable outcomes were observed after matching for baseline imbalances and excluding outliers. In support of the proposed mechanism, we present a case of sHT in which an analysis of brain tissues obtained intraoperatively showed prominent upregulation of SUR1, the target of SU drugs, in microvessels and neurons.
We conclude that, in diabetic patients with acute ischemic stroke, prior and continued use of SU drugs is associated with reduced sHT compared to those whose treatment regimen does not include SU drugs.
在缺血性卒中后发生出血性转化（HT）的患者中，残疾或死亡更为常见。在卒中大鼠模型中，磺酰脲（SU）类药物如格列本脲（采用美国名称，glyburide）通过作用于新型 SUR1 调节的 NC（Ca-ATP）通道，对肿胀和 HT 发挥保护作用。在这里，我们试图确定患有糖尿病（DM）的患者在急性缺血性卒中时使用 SU 类药物是否会影响 HT 的发生率。
我们回顾性分析了 220 例患有 DM 并伴有急性缺血性卒中的患者的数据，其中 43 例接受 SU 药物治疗并继续接受治疗，177 例未接受（对照组）。
在住院期间的中位数为 11 天内，20 名对照组患者（11%）发生症状性 HT（sHT），而 SU 组无患者发生 sHT（p=0.016）。与对照组相比，SU 组无患者死亡（对照组为 18 例，占 10%）（p=0.027）。在针对基线失衡进行匹配并排除异常值后，也观察到类似的良好结果。为了支持所提出的机制，我们提供了一个 sHT 的病例，对术中获得的脑组织进行分析显示，SU 药物的靶标 SUR1 在微血管和神经元中明显上调。
我们得出结论，在伴有急性缺血性卒中的糖尿病患者中，与不包括 SU 类药物治疗方案的患者相比，既往和持续使用 SU 类药物与减少 sHT 相关。
