Magnesium sulfate infused within 2 hours of stroke symptom onset failed to improve clinical outcomes by 3 months, according to results from the randomized, placebo-controlled Field Administration of Stroke Therapy-Magnesium trial published in the Feb. 5 issue of the New England Journal of Medicine.
The drug did not shift functional outcomes in FAST-MAG to a more favorable distribution nor, in secondary endpoints, did it change outcome scores as measured by the modified Rankin Scale or National Institutes of Health Stroke Scale.
At 3 months, a little more than half of each group had an modified Rankin Scale score of 2 or lower and about 65% of each group had a National Institutes of Health Stroke Scale score of 8 or lower, both of which indicate good functional recovery. About 15% of each group had died, Dr. Jeffrey L. Saver and his colleagues reported (N. Engl. J. Med. 2015;372:528-36).
The trial randomized 1,700 patients with suspected ischemic stroke to either magnesium sulfate or placebo infusions en route to a hospital. In a number of animal models of stroke, magnesium sulfate has been shown to exert both “vasodilatory and direct neuroprotective and glioprotective effects,” the investigators wrote.
It’s unclear why FAST-MAG didn’t replicate these earlier findings, said Dr. Saver, director of the clinical stroke program at the University of California, Los Angeles, and his coauthors. Slow transport of magnesium into the brain could be a contributing factor.
“Magnesium trafficking across the blood-brain barrier is not immediate. The concentration of magnesium in the cerebrospinal fluid peaks 4 hours after parenteral administration in the presence of an intact blood-brain barrier and more quickly in regions of focal ischemia where the blood-brain barrier is disrupted. Magnesium sulfate may not have accumulated in brain tissues quickly enough to yield a benefit despite rapid attainment of increased serum levels,” they wrote.
The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Saver has served as an unpaid consultant on a number of trials conducted by pharmaceutical companies. He had no other financial declarations with regard to the FAST-MAG study.
msullivan@frontlinemedcom.com
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