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(Stroke. 2004;35:1776.)
© 2004 American Heart Association, Inc.

Emerging Therapies

SLOW-MAG

From the University of California at San Diego, California.

Correspondence to Justin A. Zivin, 9500 Gilman Drive, La Jolla, CA 92093-0624. E-mail jzivin@ucsd.edu

Key Words: clinical neurology • clinical trials • stroke • magnesium

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Unfortunately, we have done it again. Another potentially promising method for acute stroke management has failed in a well-conducted clinical trial. In the IMAGES study,¹ 2589 patients were randomized to magnesium sulfate (MgSO₄) or placebo, with administration started within 12 hours after symptom onset. The investigators found that although the drug is safe in acute stroke patients, it did not reduce the chances of death or disability. After looking at the data for a glimmer of hope, only subcortical stroke patients appeared to benefit, and because this was only a secondary analysis, it should only be regarded as a hypothesis generator.

Why did this happen? In preparation of this large trial, there were some preclinical data showing signs of efficacy for up to 12 hours after vascular occlusion.^2–4 Then there was a dose optimization pharmacokinetic study that showed that MgSO₄ could be given in a regimen to patients, which provided levels of drug that produced neuroprotection in the rodent stroke models.⁵ The study was appropriately powered, and it was simplified to reduce the burden on the local investigators.

There were early indications that the trial would fail. For example, only 1 study was cited⁴ to show that efficacy might extend to 12 hours after vascular occlusion. However, the animal model studies can be criticized for other reasons. I admit that in previous years, I considered it sufficient to simply show that a neuroprotective agent was efficacious when administered 5 minutes after occlusion induction using our stroke models. Despite our . . . [Full Text of this Article]