Hemorrhagic transformation of ischemic stroke in diabetics on sulfonylureas

Hagen Kunte, Markus A. Busch, Katrin Trostdorf, Bernd Vollnberg, Lutz Harms, Rupal I. Mehta, Rudolf J. Castellani, Pitchaiah Mandava, Thomas A. Kent, J. Marc Simard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Objective: 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. Methods: 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). Results: 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. Interpretation: 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.

Original languageEnglish (US)
Pages (from-to)799-806
Number of pages8
JournalAnnals of neurology
Volume72
Issue number5
DOIs
StatePublished - Nov 2012

Funding

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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