Hemorrhagic transformation of ischemic stroke in diabetics on sulfonylureas
Article first published online: 27 DEC 2012
Copyright © 2012 American Neurological Association
Annals of Neurology
Volume 72, Issue 5, pages 799–806, November 2012
How to Cite
Kunte, H., Busch, M. A., Trostdorf, K., Vollnberg, B., Harms, L., Mehta, R. I., Castellani, R. J., Mandava, P., Kent, T. A. and Simard, J. M. (2012), Hemorrhagic transformation of ischemic stroke in diabetics on sulfonylureas. Ann Neurol., 72: 799–806. doi: 10.1002/ana.23680
- Issue published online: 27 DEC 2012
- Article first published online: 27 DEC 2012
- Accepted manuscript online: 25 JUN 2012 11:34AM EST
- Manuscript Accepted: 15 JUN 2012
- Manuscript Revised: 31 MAY 2012
- Manuscript Received: 15 MAR 2012
- National Heart, Lung, and Blood Institute. Grant Number: HL082517
- National Institute of Neurological Disorders and Stroke. Grant Number: NS061808
- Institute of Clinical and Translational Research at the Baylor College of Medicine
- Department of Veterans Affairs. Grant Number: VISN 16 PGP
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 NCCa-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. ANN NEUROL 2012;72:799–806