Prehospital neuroprotectant in combination with post-arrival thrombolytic therapy for acute ischemic stroke. Secondary analysis of the FAST-MAG prehospital trial.

OBJECTIVE

Prehospital neuroprotectant therapy in combination with thrombolysis is a potential treatment strategy in acute ischemic stroke allowing for earlier therapy start and bridging period until in-hospital therapies. We describe prehospital administration of magnesium sulfate (Mg) vs. placebo for neuroprotection followed by post-arrival thrombolysis (TPA).

METHODS

We analyzed subjects who received TPA in the NIH Field Administration of Stroke Therapy Magnesium (FAST-MAG) clinical trial, a phase 3 randomized clinical trial of patients presenting within 2 h of last known well time (LKWT). Primary outcome was disability measured on the modified Rankin Scale (mRS) at 90 days.

RESULTS

Among identified 401 cases, 214 received Mg and 187 received placebo followed by TPA. Mean (±SD) age was 70±13 years, 46% women, and median Los Angeles Motor Scale (LAMS) was 4 (IQR 3-5). Median LKWT to prehospital initiation time was 46 min (IQR 35-65), and 150 min (IQR 124-171) to thrombolysis. The median prehospital study infusion exposure prior to thrombolysis start was 93 (IQR 75-117) min. In patients with NIHSS >15, the Mg group had a higher proportion achieving favorable 90-day outcomes (mRS 0-2) and lower median LAMS scores compared with placebo, although these findings were not supported by overall 90-day outcomes mRS analysis and should be considered hypothesis-generating.

CONCLUSIONS

Prehospital magnesium followed by alteplase was feasible and safe but did not demonstrate a significant overall clinical benefit. The main contribution of this analysis is to quantify the substantial pre-reperfusion exposure interval achievable with prehospital neuroprotective therapy, supporting this model for future agents requiring early biological exposure before reperfusion.